Clinical trial NCT03460652
Conditions: ADHD
Sponsor: Zevra Therapeutics
Start date: 2018-03-13; Completion date: 2019-07-09
Enrollment: 282 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is a multicenter, dose-optimized, open-label safety study with KP415 in children with Attention-Deficit/Hyperactivity Disorder (ADHD).

Detailed description:
The study will consist of a Screening Period, a Dose Optimization Phase, and a Treatment Phase and a Follow-Up Visit, as follows:

* Screening Period: Subjects will undergo a screening period up to 30 days prior to entering the Dose Optimization Phase.
* Dose Optimization Phase: During the Dose Optimization Phase, subjects will be titrated to doses of 20, 30 or 40 mg KP415 based on tolerability and best individual dose-response in the opinion of the Investigator.
* Treatment Phase: Eligible subjects will receive single daily doses of KP415 for up to approximately 360 days (up to approximately 12 months). The dose of KP415 given in the Treatment Phase will be the dose of KP415 at the end of the Dose Optimization Phase. During the Treatment Phase, the dose of KP415 may be changed based on individual tolerability and best dose response (to either 20, 30, or 40 mg KP415 capsules). Safety, efficacy and sleep behavior assessments will be performed.
* Follow-Up Visit: 3 ±2 days after administration of the last dose of the Treatment Phase, subjects will enter a Follow-Up Visit to evaluate safety parameters.

Arms: arm 1: KP415 (serdexmethylphenidate \[SDX\] Cl/ d-methylphenidate \[d-MPH\] HCl) oral capsule:

28/6 mg SDX/d-MPH (molar equivalent to 20 mg d-MPH HCl), 42/9 mg SDX/d-MPH (molar equivalent to 30 mg d-MPH HCl), 56/12 mg SDX/d-MPH (molar equivalent to 40 mg d-MPH HCl)
Interventions: intervention 1: KP415 oral capsule
Intervention descriptions: intervention 1: Once-daily oral dose

Protocol documents:
SAP_002.pdf: 
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Statistical Analysis Plan
Sponsor:
KemPharm, Inc.
Protocol Title:
A Multicenter, Dose-Optimized, Open-Label Safety Study with 
KP415 in Children with Attention-Deficit/Hyperactivity Disorder
Protocol Number:
KP415.S01
Premier Research PCN:
KEMP7419
Document Version:
Final 1.0
Document Date: 
01-Aug-2018
Approvals
Role
Signatures
Date (dd-Mmm-yyyy)
Lead 
Biostatistician
Print Name: Adrienne Kuxhausen
Sign Name:
Senior Reviewer
Print Name: Valerie Smith
Sign Name: 
KemPharm, Inc.
Representative
Print Name: Rene Braeckman
Sign Name:


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 2 of 123
Document History
Not applicable.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
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Table of Contents
Approvals........................................................................................................................................ 1
Document History........................................................................................................................... 2
Table of Contents............................................................................................................................ 3
List of Tables .................................................................................................................................. 4
List of Figures................................................................................................................................. 5
1.
Overview............................................................................................................................. 6
2.
Study Objectives and Endpoints......................................................................................... 6
2.1.
Study Objectives........................................................................................................... 6
2.1.1. Primary Objective......................................................................................................... 6
2.1.2. Secondary Objectives.................................................................................................... 6
2.2.
Study Endpoints............................................................................................................ 6
2.2.1. Safety Endpoints........................................................................................................... 7
2.2.2. Efficacy Endpoints........................................................................................................ 7
2.2.3. Other Endpoint.............................................................................................................. 7
3.
Overall Study Design and Plan........................................................................................... 8
3.1.
Overall Design .............................................................................................................. 8
3.2.
Sample Size and Power................................................................................................. 8
3.3.
Study Population........................................................................................................... 8
3.4.
Treatments Administered.............................................................................................. 8
3.5.
Method of Assigning Subjects to Treatment Groups.................................................... 8
3.6.
Blinding and Unblinding............................................................................................... 8
3.7.
Schedule of Events........................................................................................................ 8
4.
Statistical Analysis and Reporting.................................................................................... 17
4.1.
Introduction................................................................................................................. 17
4.2.
Interim Analysis and Data Monitoring ....................................................................... 18
5.
Analysis Populations......................................................................................................... 18
6.
General Issues for Statistical Analysis.............................................................................. 19
6.1.
Statistical Definitions and Algorithms........................................................................ 19
6.1.1. Baseline....................................................................................................................... 19
6.1.2. Adjustments for Covariates......................................................................................... 19
6.1.3. Multiple Comparisons................................................................................................. 19
6.1.4. Handling of Dropouts or Missing Data....................................................................... 19
6.1.5. Analysis Visit Windows ............................................................................................. 20
6.1.6. Pooling of Sites........................................................................................................... 20
6.1.7. Derived Variables ....................................................................................................... 20
6.1.8. Data Adjustments/Handling/Conventions .................................................................. 21


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
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7.
Study Subjects and Demographics.................................................................................... 22
7.1.
Disposition of Subjects and Withdrawals................................................................... 22
7.2.
Protocol Violations and Deviations ............................................................................ 23
7.3.
Demographics and Other Baseline Characteristics..................................................... 23
7.4.
Exposure and Compliance .......................................................................................... 23
8.
Efficacy Analysis.............................................................................................................. 24
8.1.
Secondary Efficacy Analysis ...................................................................................... 24
9.
Safety and Tolerability Analysis....................................................................................... 25
9.1.
Adverse Events ........................................................................................................... 25
9.1.1. Adverse Events Leading to Withdrawal ..................................................................... 26
9.1.2. Deaths and Serious Adverse Events ........................................................................... 26
9.1.3. Other Significant Adverse Events............................................................................... 26
9.2.
Clinical Laboratory Evaluations ................................................................................. 27
9.3.
Vital Signs................................................................................................................... 28
9.4.
Electrocardiograms ..................................................................................................... 28
9.5.
Further Safety Evaluations.......................................................................................... 28
9.6.
Concomitant Medication............................................................................................. 28
10.
Changes from Planned Analysis ....................................................................................... 29
11.
Other Planned Analysis..................................................................................................... 29
12.
References......................................................................................................................... 30
13.
Tables, Listings, and Figures ............................................................................................ 30
13.1.
Planned Table Descriptions ........................................................................................ 30
13.2.
Efficacy Data .............................................................................................................. 31
13.3.
Safety Data.................................................................................................................. 33
13.4.
Other Data Summary Tables....................................................................................... 36
13.5.
Planned Listing Descriptions...................................................................................... 36
13.6.
Planned Figure Descriptions....................................................................................... 38
13.7.
Standard Layout for all Tables, Listings, and Figures................................................ 39
13.8.
Planned Table Shells................................................................................................... 41
13.9.
Planned Listing Shells................................................................................................. 88
13.10. Planned Figure Shells ............................................................................................... 113
Appendix 1: Premier Research Library of Abbreviations .......................................................... 114
List of Tables
Table 1: Schedule of Events (Screening [all subjects] and Dose Optimization Phase [new 
subjects only])....................................................................................................................... 10


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
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Table 2: Schedule of Events (Treatment Phase [First 6 Months; All Subjects]).......................... 13
Table 3: Schedule of Events (Treatment Phase [Second 6 Months], and Early Termination and 
Follow-Up Visits [All Subjects]).......................................................................................... 14
Table 4: Demographic Data Summary Tables and Figures.......................................................... 31
Table 5: Efficacy Data .................................................................................................................. 31
Table 6: Safety Data...................................................................................................................... 33
Table 7: Planned Listings.............................................................................................................. 36
List of Figures
Figure 1: Standardized Layout...................................................................................................... 40


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
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1.
Overview
This statistical analysis plan (SAP) describes the planned analysis and reporting for KemPharm, 
Inc. protocol number KP415.S01 (A Multicenter, Dose-Optimized, Open-Label Safety Study 
with KP415 in Children with Attention-Deficit/Hyperactivity Disorder), dated 26-Apr-2018,
Amendment #2. Reference materials for this statistical plan include the protocol and the 
accompanying sample data collection documents. Operational aspects related to collection and 
timing of planned clinical assessments are not repeated in this SAP unless relevant to the planned 
analysis.
The structure and content of this SAP provides sufficient detail to meet the requirements 
identified by the Food and Drug Administration (FDA), European Medicines Agency (EMA),
and International Conference on Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical 
Trials1. All work planned and reported for this SAP will follow internationally accepted 
guidelines, published by the American Statistical Association2and the Royal Statistical Society3,
for statistical practice.
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. Also, post-hoc exploratory analyses not 
necessarily identified in this SAP may be performed to further examine study data. Any post-hoc 
or unplanned, exploratory analysis performed will be clearly identified as such in the final CSR.
The statistical plan described hereafter is an a priori plan. It will be submitted to file prior to any 
unblinded inferential or descriptive analysis of data pertaining to KemPharm, Inc.’s study 
KP415.S01.
2.
Study Objectives and Endpoints
2.1.
Study Objectives
2.1.1. Primary Objective
The primary objective is to determine the safety and tolerability of KP415 in treating children 
with attention-deficit hyperactivity disorder (ADHD).
2.1.2. Secondary Objectives
The secondary objectives are to determine the efficacy and changes in sleep behavior during 
KP415 treatment in children with ADHD.
2.2.
Study Endpoints
This study is primarily an open-label safety study in the target patient population after 
approximately 12 months of daily oral doses of KP415 capsules, or after a shorter duration if the 
study is stopped at an interim analysis. Therefore, the primary endpoint is safety.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
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2.2.1. Safety Endpoints
The safety endpoints of this study include the following for all subjects:
The occurrence of treatment-emergent adverse events (TEAEs) will be assessed starting 
following the first dose of study drug, and ending with the Follow-Up Visit or Early 
Termination Visit. 
Physical examinations will be performed at the first visit (at Screening, before the first 
dose of study drug), after approximately 6 months of treatment (Visit 11), and at the end 
of the Treatment Phase (Visit 17, End of Treatment [EOT]) or at Early Termination. 
Clinical laboratory tests will be performed at the first visit (at Screening, before the first 
dose of study drug), after approximately 6 months of treatment (Visit 11), and at the end 
of the Treatment Phase (Visit 17, EOT) or at Early Termination.
Electrocardiogram (ECG) parameters will be collected at the first visit (at Screening, 
before the first dose of study drug), after approximately 6 months of treatment (Visit 11), 
and at the end of the Treatment Phase (Visit 17, EOT) or at Early Termination. 
Vital signs, height, weight, and body mass index (BMI) will be collected at each study 
visit. 
The Columbia-Suicide Severity Rating Scale (C-SSRS) will be performed at each study 
visit. 
2.2.2. Efficacy Endpoints
The efficacy endpoints of this study include the following:
During the Dose Optimization Phase (new subjects only): 
o
Clinical Global Impressions–Severity (CGI-S) will be assessed at each visit 
(Screening to Visit 5). Attention-Deficit Hyperactivity Disorder Rating Scale 5
(ADHD-RS-5) will be administered at Visits 2 through Visit 5. Clinical Global 
Impressions–Improvement (CGI-I) will be assessed at Visits 3, 4, and 5 (since 
CGI-I is an ADHD improvement assessment, it will not be assessed at Screening 
and at Visit 2).
During the Treatment Phase (all subjects): 
o
ADHD-RS-5 and CGI-S will be assessed at each visit (Visit 5 to Visit 17, EOT).
2.2.3. Other Endpoint
The modified, abbreviated Children’s Sleep Habits Questionnaire (CSHQ) will be used to assess 
the sleep behavior in the Dose Optimization Phase for new subjects (Visit 2) and in the 
Treatment Phase for all subjects (Visit 5 to Visit 17). The baseline will be measured before the 
first dose of study drug, at Visit 2 for new subjects and at Visit 5 for roll-over subjects.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
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3.
Overall Study Design and Plan
3.1.
Overall Design
3.2.
Sample Size and Power
No formal sample size calculations were conducted. It was determined that approximately 200 
subjects are adequate to satisfy the primary objective of the study, which is to determine the 
safety and tolerability of KP415 in treating children with ADHD for at least 6 months. Assuming 
a maximum dropout rate of 20% over 6 months, approximately 250 subjects will be enrolled.
Subjects will be rolled over from Study KP415.E01 and to reach the targeted number of subjects, 
new subjects will be enrolled as well. Subjects who fail Screening and new subjects who 
terminate early during the Dose Optimization Phase may be replaced. Subjects who terminate 
early in the Treatment Phase will not be replaced.
3.3.
Study Population
The study population includes subjects rolled over from Study KP415.E01 (aged 6 to 13) or new 
subjects (aged 6 to 12) with ADHD who meet the inclusion/exclusion criteria listed in the 
protocol.
3.4.
Treatments Administered
All subjects will be administered 1 unblinded KP415 capsule once daily in the Treatment Phase. 
The dose of KP415 will be determined by the optimal dose of KP415 identified at the end of the 
Dose Optimization Phase, either 20, 30, or 40 mg/day KP415.
3.5.
Method of Assigning Subjects to Treatment Groups
Dose Optimization Phase (new subjects only): All eligible subjects will start on a dose of 
30 mg/day open-label KP415 and the KP415 dose will be titrated to either 20, 30 or 40 mg/day 
based on tolerability and best individual dose-response in the opinion of the Investigator.
Treatment Phase (all subjects): Roll-over subjects from Study KP415.E01, and new subjects 
who completed the Dose Optimization Phase (and passed the eligibility criteria for the Treatment 
Phase will be enrolled at Visit 5 (start of the Treatment Phase) for treatment with the optimized 
dose of KP415 capsules. During the Treatment Phase, based on individual tolerability and dose 
response, the daily dose of KP415 may be changed to any of the allowed dose levels (20, 30, or 
40 mg/day) at the Investigator’s discretion.
3.6.
Blinding and Unblinding
This is an open-label study. Study treatments will not be blinded.
3.7.
Schedule of Events
A detailed schedule of events for the study is provided in Table 1 (Screening [all subjects] and 
Dose Optimization Phase [new subjects only]), Table 2 (Treatment Phase, first 6 months [all 
subjects]), and Table 3 (Treatment Phase, second 6 months; Early Termination; and Follow-up


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
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Version 0.1    |
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Visits [all subjects]).


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
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Version 0.1    |
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Table 1: Schedule of Events (Screening [all subjects] and Dose Optimization Phase [new 
subjects only])
ASSESSMENTS
NEW
SCREENING 
PHASE 22
ROLLOVER
OPEN-LABEL
DOSE OPTIMIZATION PHASE 21, 22
(NEW SUBJECTS ONLY)
Study Day
-30 to 
-1
-30 to 
-1
0
1-6
(±3 
Days)
7
(±3 
Days)
8-13
(±3 
Days)
14
(±3 
Days)
15-20
(±3 
Days)
Visit Number
1A
1B24
2
3
4
Parental Permission/Written or Verbal 
Assent 
X
X
ADHD Diagnosis and Confirmation 1
X
Capsule Swallowing Test 2
X
Inclusion/Exclusion
X
X
X
X
X
Demographics
X
X
Medical History 3
X
X
X
Physical Examination
X
X
Body Weight, Height, BMI 4
X
X
Vital Signs 5
X
X
X
X
X
12-Lead ECG 6
X
X
Chemistry/Hematology/Urinalysis 
(under fasting conditions)
X
X
Urine Alcohol/Drugs of Abuse Screen 7
X
X
Urine MPH Screen 8
X
X
Pregnancy Test 9
X
X
X
C-SSRS 10
X
X
X
X
X
Washout ADHD Meds 11
X
Open-Label KP415 Dosing 12
X
X
X
X
X
Drug Accountability & Compliance 
Assessment 13
X
X
ADHD-RS-5 14
X
X
X
MINI-KID 15
X
CGI-S 16
X
X
X
X
CGI-I 17
X
X
CSHQ 18
X
Adverse Events 19
X
X
X
X
X
Concomitant Medications 20
X
X
X
X
BMI = Body Mass Index; ECG = Electrocardiogram; MPH = methylphenidate; see footnotes for other 
abbreviations.
1.
ADHD Diagnosis based on the Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) criteria for a 
primary diagnosis of ADHD (combined, inattentive, or hyperactive/impulsive presentation) and confirmed by 
the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). 
2.
Capsule Swallowing Test: Subjects must be able to comply with one of the following: 


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
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a)
Subjects will take a size 3 capsule with up to 240 mL of water at Screening. The capsule may not contain 
any active drug substance. Subjects must be able to easily swallow the size 3 capsule to be eligible for 
further study participation. This is not required for subjects who have previously participated in the 
KP415.E01 study. 
b)
If subjects are unable to demonstrate that they can swallow size 3 capsules, they must agree to take the 
capsule contents sprinkled over a small amount of applesauce or added to a small amount of water during 
the study. 
Any of the methods of administration may be used on any day of the study, but if subjects plan to take study 
drug as the whole capsule, subjects will need to have demonstrated that they are able to swallow size 3 capsules 
at Screening or any time during the study (or have been previously participated in Study KP415.E01). 
3.
Medical History: A complete medical history including chronic conditions, relevant surgical procedures (with 
start date), history of drug and alcohol use. As part of Medical History for Visit 1B (and with more details 
captured in the database), record treatment with study drug in Study KP415.E01 with regards to dose, duration, 
date of last dose (Visit 6 in Study KP415.E01), last visit in Study KP415.E01 (Visit 7 in Study KP415.E01), etc. 
4.
Height will be recorded in centimeters (cm) with the subject’s shoes removed. Body weight will be measured in 
kilograms (kg); subjects will remain in their normal clothing with shoes and jacket (and/or outer clothing) 
removed. 
5.
Vital sign measurements will be obtained after the subject has been seated for at least 3 minutes. Vital signs will 
include sitting blood pressure (systolic and diastolic measurements), pulse rate (beats per minute), respiratory 
rate (breaths per minute), and oral temperature. Vital signs will be collected once at each visit. 
6.
Electrocardiogram (ECG): A 12-lead ECG will be obtained after the subject has been in the supine position for 
at least 3 minutes. Abnormal ECGs may be repeated for confirmation in which case only the repeated ECG will 
be recorded. The QT interval corrected for heart rate will be calculated with Fridericia’s formula (QTcF). For 
roll-over subjects, if the Screening Visit (Visit 1B) occurs on the same day as the Follow-Up Visit (Visit 7) of 
Study KP415.E01, one ECG will be obtained to be used in both studies. If Visit 1B occurs later, after Visit 7 in 
E01, a new ECG will be obtained at Visit 1B as baseline for the current study. 
7.
Urine Screen for Alcohol and Drugs of Abuse: Urine samples will be tested for alcohol, and drugs of abuse 
(amphetamines, methamphetamines, benzodiazepines, barbiturates, cannabinoids, cocaine, opioids including 
oxycodone) at Screening (Visit 1A or 1B). If the urine test is positive for any of the analytes at Screening, the 
subject will be excluded from study participation, with the exception of the following: Depending on a subject's 
current ADHD medication at Screening, the urine screen at Screening may test positive for ADHD medications 
such as amphetamines and methamphetamines. All ADHD medications must be washed out by Visit 2 for new 
subjects and Visit 5 for roll-over subjects. 
8.
Urine Screen for Methylphenidate (MPH): For new subjects, urine samples will be tested for MPH at Screening 
(Visit 1A) and Visit 2. A urine dipstick (eg, NarcoCheck®) will be used to screen for the presence of MPH in 
the urine. If a subject's current ADHD medication at Screening contains MPH, the urine screen at Screening 
(Visit 1A, new subjects) may test positive for MPH. All ADHD medications must be washed out by Visit 2 for 
new subjects and Visit 5 for roll-over subjects (MPH urine screen must test negative). 
9.
-hCG pregnancy test will be
performed at Screening. A urine pregnancy test will be performed at Visit 2. A positive pregnancy test at 
Screening or before the last dose of study drug will exclude a subject from further participation in the study. 
10. Columbia-Suicide Severity Rating Scale (C-SSRS): The “Children’s Baseline/Screening” version will be 
assessed at Screening, and the “Children’s Since Last Visit” version will be assessed at all other visits. Subjects 
who have, in the opinion of the Investigator, clinically significant suicidal ideation/behavior, based on history of 
attempted suicide and the C-SSRS assessment at Screening or at any time before the last dose of study drug, 
will be excluded from further participation in the study. 
11. All Subjects must wash out ADHD medications prior to Visit 2. Stimulant ADHD medications (with the 
exception of study drug), including herbal medications, are prohibited from 5 days prior to Visit 2 for new 
subjects and prior to Visit 5 for roll-over subjects to the end of the Follow-Up Visit or Early Termination Visit. 
Before or on the day during the screening period that subjects will need to start the washout of their ADHD 
medications (for example, 5 days before Visit 2 for stimulants), study site staff will contact the subject’s 
parent/guardian by phone to remind them of the washout (“washout phone call”). Non-Stimulant ADHD 
medications are prohibited from 14 days prior to the start of the Dose Optimization Phase (Visit 2) to the end of 
the Follow-Up Visit or Early Termination Visit. Other prohibited medications with their associated time 
windows when they are prohibited are listed in the protocol. 


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
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12. KP415 Dose Optimization: Subjects will begin taking open-label KP415 at home the morning following Visit 2. 
The starting dose of KP415 (Days 1-7 ±3 days) will be 30 mg/day. KP415 dose adjustments, if needed, will be 
performed at approximately weekly intervals between visits (at Visits 3 and 4). Actual visit dates may deviate 
from exactly being spaced 7 days apart such that the total duration of the Dose Optimization Phase is 3 weeks 
(21 days) ±3 days. The daily doses of KP415 used in the Dose Optimization Phase will be 20, 30, and 40 mg 
4, based on the CGI scores, interview with the 
parent/guardian/caregiver, and safety data, the Investigator will evaluate the subject’s therapeutic responses and 
tolerability to treatment and decide whether the current KP415 dose should be increased, decreased, or remain 
the same for the next week of dosing. If subjects experience symptoms of intolerance during the at-home 
treatment, they must contact the clinical site, and, at the discretion of the Investigator, their KP415 dose may be 
adjusted before the next scheduled visit. Unscheduled visits between Visits 2, 3, and 4 are allowed as needed, at 
the discretion of the Investigator. 
13. Drug Accountability & Compliance Assessment: All study drug will be recorded by each site’s pharmacy staff 
member or Investigator-delegated employee. A record of the study drug accountability will be prepared and 
kept by the clinical site. 
14. ADHD-Rating Scale-5 (ADHD-RS-5) assessment: 1 assessment at the indicated visits. 
15. Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID): For confirmation of 
ADHD diagnosis at Screening. 
16. Clinical Global Impressions–Severity (CGI-S) scale assessment: 1 assessment at the indicated visits. 
17. Clinical Global Impressions–Improvement (CGI-I) scale assessment: 1 assessment at the indicated visits. 
18. Children’s Sleep Habits Questionnaire (CSHQ) assessment: 1 assessment at Visit 2. 
19. Adverse Events: To be assessed and recorded in the eCRF following the first dose of open-label drug (KP415), 
on Day 1, through either Follow-Up or Early Termination. Subject’s parent/guardian will be instructed to 
contact the study site for the reporting of AEs during the dosing periods at home. 
20. Concomitant Medications: new and/or changed medications and dose, medical treatments and/or therapies will 
be recorded at Screening through either Follow-Up or Early Termination. 
21. Actual visit dates in the Dose Optimization Phase may deviate from exactly being spaced 7 days apart such that 
the total duration of the Dose Optimization Phase ranges between 18 and 24 days (21 ±3 days). Any allowed 
deviation (up to 3 days in total) of the targeted 21-day Dose Optimization Phase will be carried over into the 
actual days for the subsequent visits. 
22. Subjects who meet withdrawal criteria post-dose during the Dose Optimization Phase (after at least one dose of 
study drug is administered) will complete Early Termination procedures as listed in the Schedule of Events in 
Table 3. This includes subjects who do not meet the eligibility criteria to continue in the Treatment Phase. At 
the discretion of the Investigator, ensuring the safety of the subjects, any Early Termination procedures that 
were already performed on the same day as part of the procedures of the Dose Optimization Phase, do not need 
to be repeated. Subjects who withdraw early from the study and complete the ET procedures will not return for 
a Follow-Up Visit. Therefore, the ET Visit is the End-of-Study (EOS) for these subjects. 
23. The procedures at Screening are different between subjects rolled over from Study KP415.E01 and new 
subjects. Therefore, the Screening Visit for roll-over subjects is designated as Visit 1B, and for new subjects is 
designated Visit 1A. Visits 2, 3 and 4 are not needed for subjects rolled over from Study KP415.E01 because 
their optimum dose was determined in the Dose Optimization Phase of Study KP415.E01. Therefore, roll-over 
subjects from Study KP415.E01 will start with Visit 1B as the first visit of the current study, followed by Visit 5 
as the next visit (roll-over subjects will not have Visits 2, 3 and 4). 
24. The Screening Visit for roll-over subjects (Visit 1B) may occur on the same day as the EOS (Visit 7, 
Follow-Up) in Study KP415.E01 or later, and must occur within 30 days before Visit 5 in the current study. For 
roll-over subjects, the Investigator has the option to use the clinical laboratory (clinical chemistry, hematology 
and urinalysis) results from the Follow-Up Visit in Study KP415.E01 (Visit 7) in lieu of collecting new blood 
samples at Screening (Visit 1B) in the current study, as long as the clinical laboratory samples from the E01 
study were collected within 30 days prior to Screening (Visit 1B) in the current study. For all roll-over subjects 
who are children of childbearing potential, a blood sample for the measurement of a serum pregnancy test is 
needed at Visit 1B. For other assessments required at Visit 1B (C-SSRS, for example), the Visit 7 assessments 
from the E01 study (if collected) can be used as long as Visit 1B is conducted on the same day as Visit 7 in the 
E01 study. Visit 7 clinical laboratory samples collected during KP415.E01 (also used as the Visit 1B results) are 
not required to be collected under fasting conditions. During Visit 1B of the current study, the study site will 
document whether these samples were collected under fasting/non-fasting conditions, and this will be recorded 
in the database. 


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Table 2: Schedule of Events (Treatment Phase [First 6 Months; All Subjects])
ASSESSMENTS
OPEN-LABEL
TREATMENT PHASE 19
Study Day
0
1-29
(±5 
Days)
30
(±5 
Days)
31-59
(±5 
Days)
60
(±5 
Days)
61-89
(±5 
Days)
90
(±5 
Days)
91-
119
(±5 
Days)
120
(±5 
Days)
121-
149
(±5 
Days)
150
(±5 
Days)
151-
179
(±5 
Days)
180
(±5 
Days)
Visit Number
5
6
7
8
9
10
11
Inclusion/Exclusion 
X
Medical History 1
X
Physical Examination 2
X
Body Weight, Height, BMI 3
X
X
X
X
X
X
X
Vital Signs 4
X
X
X
X
X
X
X
12-Lead ECG 5
X
Chemistry/Hematology/Urinalysis 
X
Urine MPH Screen (roll-overs) 6
X
Pregnancy Test 7
X
X
X
X
X
X
X
C-SSRS 8
X
X
X
X
X
X
X
Prohibited Medications 9
X
X
X
X
X
X
X
X
X
X
X
X
X
Eligibility Criteria (new subjects) 10
X
Enrollment in Treatment Phase 11
X
Open-Label KP415 Dosing 12
X
X
X
X
X
X
X
X
X
X
X
X
Drug Accountability & Compliance 
Assessment 
X22
X
ADHD-RS-5 13
X
X
X
X
X
X
X
CGI-S 14 
X
X
X
X
X
X
X
CGI-I 15
X
CSHQ 16
X
X
X
X
X
X
X
Adverse Events 17
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant Medications 18
X
X
X
X
X
X
X
Interim Analysis 23
X
EOS = End of Study; ET = Early Termination; BMI = Body Mass Index; ECG = Electrocardiogram; see footnotes for other abbreviations.


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Table 3: Schedule of Events (Treatment Phase [Second 6 Months], and Early Termination and Follow-Up Visits [All Subjects])
ASSESSMENTS
OPEN-LABEL
TREATMENT PHASE 19
ET 21
(EOS) 
ET 21
(EOS) 
Study Day
181-
209
(±5 
days)
210
(±5 
days)
211-
239
(±5 
days)
240
(±5 
days)
241-
269
(±5 
days)
270
(±5 
days)
271-
299
(±5 
days)
300
(±5 
days)
301-
229
(±5 
days)
330
(±5 
days)
331-
359
(±5 
days)
360
20
(±5 
days)
-
343-
383
(±2 
days)19
Visit Number
12
13
14
15
16
17
-
18
Physical Examination 2
X
X
Body Weight, Height, BMI 3
X
X
X
X
X
X
X
X
Vital Signs 4
X
X
X
X
X
X
X
X
12-Lead ECG 5
X
X
Chemistry/Hematology/
Urinalysis (under fasting 
conditions)
X
X
Pregnancy Test 7
X
X
X
X
X
X
X
X
C-SSRS 8
X
X
X
X
X
X
X
X
Prohibited Medications 9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Open-Label KP415 Dosing 12
X
X
X
X
X
X
X
X
X
X
X
X
Drug Accountability & 
Compliance Assessment 
X
X
X
X
X
X
X
ADHD-RS-5 13
X
X
X
X
X
X
CGI-S 14 
X
X
X
X
X
X
CGI-I 15
CSHQ 16
X
X
X
X
X
X
Adverse Events 17
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant Medications 18
X
X
X
X
X
X
X
X
EOS = End of Study; ET = Early Termination; BMI = Body Mass Index; ECG = Electrocardiogram; see footnotes for other abbreviations.
1. Medical History: A complete medical history including chronic conditions, relevant surgical procedures (with start date), history of drug and alcohol use. 
2. Physical examination at Visit 11, and at Visit 17 (EOT) or at Early Termination (if possible).
3. Body weight, height and BMI at each visit. Height will be recorded in centimeters (cm) with the subject’s shoes removed. Body weight will be measured in 
kilograms (kg); subjects will remain in their normal clothing with shoes and jacket (and/or outer clothing) removed. 


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4. Vital sign measurements will be obtained after the subject has been seated for at least 3 minutes. Vital signs will include sitting blood pressure (systolic and 
diastolic measurements), pulse rate (beats per minute), respiratory rate (breaths per minute), and oral temperature. Vital signs will be collected once at each visit. 
5. Electrocardiogram (ECG): A 12-lead ECG will be obtained after the subject has been in the supine position for at least 3 minutes. Abnormal ECGs may be 
repeated for confirmation in which case only the repeated ECG will be recorded. The QT interval corrected for heart rate will be calculated with Fridericia’s 
formula (QTcF). 
6. Urine Screen for Methylphenidate (MPH): Urine samples will be tested for MPH at Visit 5 for roll-over subjects. A urine dipstick (e.g., NarcoCheck®) will be 
used to screen for the presence of MPH in the urine. All ADHD medications must be washed out by Visit 5 for roll-over subjects. Subjects with a positive MPH 
urine screen at Visit 5 will be excluded from further participation in the study or may be retested at a later date, and may be enrolled if the MPH urine screen 
retest is negative as long as the Screening Window is adhered to. 
7. A urine pregnancy test will be performed for female subjects of childbearing potential at all visits during the Treatment Phase, and at Early Termination or 
Follow-Up. A positive pregnancy test before the last dose of study drug will exclude a subject from further participation in the study. 
8. Columbia Suicide Severity Rating Scale (C-SSRS): The “Children’s Since Last Visit” version will be assessed at all visits the Treatment Phase, and at Early 
Termination or Follow-Up. Subjects who have, in the opinion of the Investigator, clinically significant suicidal ideation/behavior, based on history of attempted 
suicide and the C-SSRS assessment at Screening or at any time before the last dose of study drug, will be excluded from further participation in the study. 
9. Stimulant ADHD medications (with the exception of study drug), including herbal medications, are prohibited from 5 days prior to Visit 5 to the end of the 
Follow-Up Visit or Early Termination Visit. 
Non-Stimulant ADHD medications are prohibited from 14 days prior to the start of Visit 5 to the end of the Follow-Up Visit or Early Termination Visit. Other 
prohibited medications with their associated time windows when they are prohibited are listed in the protocol body text. 
10. At Visit 5, for new patients, the Investigator will evaluate the eligibility criteria based on assessments in the Dose Optimization Phase, for continuation into 
the subsequent Treatment Phase. For subjects eligible for the Treatment Phase, the optimal daily KP415 dose will be used as the daily KP415 dose in the 
Treatment Phase. This is not needed for subjects rolled over from Study KP415.E01 because their optimum dose was determined in the Dose Optimization Phase 
of Study KP415.E01. Rolled-over subjects from Study KP415.E01 will start with Visit 1B as the first visit of the current study, followed by Visit 5 as the next 
visit (rolled-over subjects will not have Visits 2, 3, and 4). 
11. Enrollment in the Treatment Phase: Subjects able to tolerate at least 20 mg/day of KP415 and with an adequate dose-response will be enrolled into the 
Treatment Phase. The determination of tolerability and adequate dose-response will be determined in Study KP415.E01 for subjects rolled over from Study
KP415.E01 (they will need to have completed Study KP415.E01), or at the end of the Dose Optimization Phase in the current study for new subjects. Subjects 
rolled over from Study KP415.E01 will be enrolled in the Treatment Phase of the current study (Visit 5) within 45 days after the last dose of study drug in Study 
KP415.E01 (Visit 6 in Study KP415.E01). New subjects will continue to the Treatment Phase immediately after the end of the Dose Optimization Phase in the 
current study. Subjects not rolled over from Study KP415.E01 within 45 days of the last dose of study drug, may be enrolled in the current study as new subjects 
(they will need to start with Screening and Dose Optimization Phase). At the start of the Treatment Phase (Visit 5), the appropriate open-label study drug to be 
taken at home once-a-day in the morning on each of the days of the Treatment Phase until the next visit will be dispensed to the subjects. 
12. Study Drug Administration: All subjects eligible to participate in the Treatment Phase will receive non-blinded oral capsules with active KP415 drug (one 
capsule). The dose level is an optimized KP415 dose of 20, 30, or 40 mg determined at the end of the Dose Optimization Phase in Study KP415.E01 for rolled-
over subjects from Study KP415.E01, or as determined at the end of the Dose Optimization Phase in the current study for new subjects. 
Based on individual tolerability and dose-response during the Treatment Phase, at the discretion of the Investigator, the KP415 dose may be changed (increased 
or decreased, but one of the 3 dose levels of 20, 30, or 40 mg KP415 capsules). All study drugs will be given orally. Subjects will take study drug (one 
capsule/day) in the morning at home under supervision of their parent or legal guardian. The final dose of study drug will be administered on the last day of the 
Treatment Phase (Day 360 ±20 days; Visit 17). If the study is stopped earlier based on the stopping rules, the last day of the Treatment Phase (Visit 17) may 
occur earlier than Day 360 for some or all subjects. Study drug will be taken orally with up to 210-240 mL of water. The capsule needs to be swallowed whole 


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(without crushing, cutting, crushing, chewing, opening, or dissolving) or may be taken by sprinkling the contents of the capsule over a small amount of 
applesauce, or putting the contents in a small amount of water. 
13. ADHD-Rating Scale-5 (ADHD-RS-5) assessment: 1 assessment at the indicated visits. 
14. Clinical Global Impressions–Severity (CGI-S) scale assessment: 1 assessment at the indicated visits. 
15. Clinical Global Impressions–Improvement (CGI-I) scale assessment: 1 assessment at Visit 5 for new subjects only. 
16. Children’s Sleep Habits Questionnaire (CSHQ) assessment: 1 assessment at the indicated visits. 
17. Adverse Events: To be assessed and recorded in the eCRF following the first dose of open-label drug (KP415), through either Early Termination or Follow-
Up. Subject’s parent/guardian will be instructed to contact the study site for the reporting of AEs while away from the study site. 
18. Concomitant Medications: new and/or changed medications and dose, medical treatments and/or therapies will be recorded at Visit 5 through either Follow-
Up or Early Termination. 
19. To allow flexibility in scheduling visits, actual visit dates for individual subjects in the Treatment Phase may deviate from exactly being spaced 30 days apart 
(up to 30 ±5 days from the previous visit) such that the total duration of the Treatment Phase may be in the range of 360 ±20 days (340-380 days from Visit 5 to 
Visit 17). The Follow-Up Visit (3 days after the last dose) therefore falls between Day 343 and Day 383, but has its own window of ±2 days added. 
20. The end of the Treatment Phase is on Day 360 ±20 days (Visit 17), after all post-dosing procedures are completed. 
21. Subjects who meet withdrawal criteria post-dose during the Treatment Phase (after at least one dose of study drug is administered) will complete Early 
Termination procedures. At the discretion of the Investigator, ensuring the safety of the subjects, any Early Termination procedures that were already performed 
on the same day as part of the procedures of the Treatment Phase, do not need to be repeated. Subjects who withdraw early from the study and complete the ET 
procedures will not return for a Follow-Up Visit. Therefore, the ET Visit is the End-of-Study (EOS) for these subjects. 
22. Drug Accountability & Compliance Assessment: All study drug will be recorded by each site’s pharmacy staff member or Investigator-
delegated employee. A record of the study drug accountability will be prepared and kept by the clinical site at each visit for subjects receiving study drug since 
the previous visit (including drug accountability at Visit 5 for drug returned from the last week of the Dose Optimization Phase, by new subjects). 
23. An interim analysis of the safety data will be conducted after approximately all subjects remaining in the study have completed 180 days (approximately 6 
months) of treatment. After the completion of the interim analysis, based on the acceptance of the clinical and nonclinical safety database from the current study 
and other studies, the Sponsor may stop the study. Treatment in the current study will continue as planned while the interim analysis is conducted. If the decision 
is made to stop the study, all subjects remaining in the study will undergo the EOT Visit (with safety evaluations including fasting safety labs and ECGs) and a 
Follow Up Visit. 


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4.
Statistical Analysis and Reporting
The analyses contained in this Statistical Analysis Plan will assess the safety and efficacy 
of KP415 and will be included in the CSR. The final analysis will be performed after 
database lock when all subjects have been followed through Visit 18 (Days 343-383 ±2
days), unless the study is stopped early (see Section 4.2 for stopping rules).
The protocol will include an interim analysis after approximately all subjects remaining 
in the study have completed 180 days (approximately 6 months) of treatment (Visit 11). 
The focus of the interim analysis will be the safety assessments during the first 6 months 
of treatment in the Treatment Phase. The table, figure, and listing (TLF) shells that will 
be used for both the interim and final analyses are contained in this SAP. See Section 4.2
for more details.
4.1.
Introduction
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, 
and graphical representations will be performed primarily using SAS (release 9.4 or 
higher). If the use of other software is warranted, the final statistical methodology report 
will detail what software was used for what purposes.
Continuous (quantitative) variable summaries will include the number of subjects (n)
with non-missing values, mean, standard deviation (SD), coefficient of variation (CV%), 
median, minimum, and maximum.
Categorical (qualitative) variable summaries will include the frequency and percentage of 
subjects who are in the particular category or each possible value, as well as 95% 
confidence intervals (CIs). In general, the denominator for the percentage calculation will 
be based upon the total number of subjects in the study population for the treatment,
unless otherwise specified. The denominator for by-visit displays will be the number of 
subjects in the relevant study population and treatment with non-missing data at each 
visit.
The minimum and maximum will be reported with the same degree of precision (ie, the 
same number of decimal places) as the observed data. Measures of location (mean and 
median) will be reported to 1 degree of precision more than the observed data and 
measures of spread (SD) will be reported to 2 degrees of precision more than the 
observed data.
Percentages will be presented to 1 decimal place, unless otherwise specified.
Unless otherwise indicated, all statistical tests will be conducted at the 0.05 significance 
level using 2-tailed tests, and P values will be reported. Corresponding 95% CIs will be 
presented for statistical tests.
A P value of 0.10 but > 0.05 will be considered evidence of a trend. All formal 
statistical comparisons for continuous variables will be based on the t-test with unequal 
variances if data is normally distributed. If data is not normally distributed, the non-
parametric Wilcoxon/Mann-Whitney rank-sum test will be used. All formal statistical 


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comparisons for categorical or binary variables will be based on the Chi-square test or 
Fisher’s exact test. Wilson confidence intervals for binomial proportions and differences 
in binomial proportions will be computed.
Summaries of disposition and efficacy will be presented overall, by any dose of KP415. 
For safety summaries presented by treatment, the dose received at the beginning of the 
Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. For the dose optimization phase tables, the 
optimized dose is presented. If a subject receives a lower dose than planned due to 
tolerability, this will be mentioned in a footnote.
4.2.
Interim Analysis and Data Monitoring
An interim analysis of the safety data will be conducted after approximately all subjects 
remaining in the study have completed 180 days (approximately 6 months) of treatment 
(Visit 11). The focus of the interim analysis will be the safety assessments (primary 
endpoints) during the first 6 months of treatment in the Treatment Phase. The safety data will 
be analyzed using the same statistical methods as planned for the main analysis after 
completion of the study. The results from the interim safety analysis will be used to 
determine whether or not the study can be stopped. All other endpoints (including the 
secondary endpoints) and assessments will also be analyzed as part of the interim analysis.
Tables that will be presented in the interim analysis will be flagged in the table of contents.
The study may be stopped for any of the following reasons, whichever comes first: 
1. After the completion of the interim analysis, based on the acceptance of the clinical 
and nonclinical safety database from the current study and other studies, the Sponsor 
may stop the study. Treatment in the current study will continue as planned while the 
interim analysis is conducted. If the decision is made to stop the study, all subjects 
remaining in the study will undergo the EOT Visit (with safety evaluations including 
fasting safety labs and ECGs) and a Follow-Up Visit. 
2. After approximately 100 subjects have completed 360 days (approximately 1 year) 
of treatment. Other subjects remaining in the study (treated at that time for less than 
360 days) will undergo the EOT Visit (with safety evaluations including fasting 
safety labs and ECGs) and a Follow-Up Visit. 
5.
Analysis Populations
The following analysis populations are planned for this study:
Treatment-phase Safety Population: The Treatment-phase Safety Population 
will include all enrolled subjects who received at least 1 dose of study medication 
in the Treatment Phase and had at least 1 post-dose safety assessment in the 
Treatment Phase. All baseline and safety data (the latter during the Treatment 
Phase) will be analyzed using this population.
Efficacy Population: The Efficacy Population will include all enrolled subjects who 
received at least 30 days of study medication in the Treatment Phase, who had 


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adequate data to assess the change from baseline of the efficacy parameters, and who 
had no protocol deviations that could affect the efficacy parameters. All efficacy 
analyses and sleep behavior results (via CSHQ) across the Treatment Phase will be 
analyzed using this population.
Dose-optimization Safety Population: The Dose-optimization Safety Population 
will include all enrolled subjects in the Dose Optimization Phase (“New 
Subjects”) who received at least one dose of study medication in the Dose 
Optimization Phase and had at least one post-dose safety assessment in the Dose 
Optimization Phase. All data from the Dose Optimization Phase will be analyzed 
using this population.
6.
General Issues for Statistical Analysis
6.1.
Statistical Definitions and Algorithms
6.1.1. Baseline
The baseline for the safety parameters (physical examinations, vital signs, height, weight, 
BMI, ECG parameters, clinical laboratory tests, and C-SSRS scores) will be the last 
observation recorded prior to the first dose of study drug. This is measured at either Visit 1A
or Visit 2 for new subjects and Visit 1B for roll-over subjects.
The baseline for ADHD-RS-5, CGI-S, and CSHQ will be measured at Visit 5 for roll-over 
subjects and at Visit 2 for new subjects.
6.1.2. Adjustments for Covariates
Where statistical modelling is performed, the baseline value of that assessment will be 
used as a covariate.
6.1.3. Multiple Comparisons
No adjustments will be made for multiple comparisons; all analyses will be conducted at 
6.1.4. Handling of Dropouts or Missing Data
Subjects who withdraw from the study during the Treatment Phase will not be replaced. 
Subjects who withdraw from the study during the Dose Optimization Phase may be replaced.
Missing data will not be imputed for safety analyses.
For the analysis of efficacy, a sensitivity analysis will be performed in which missing 
ADHD-RS-5, CGI-S, CGI-I, and CSHQ scores during the Dose Optimization Phase and 
Treatment Phase will be imputed using Last Observation Carried Forward (LOCF).


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6.1.5. Analysis Visit Windows
For all analyses, unscheduled and/or repeated measurements will only be included if a 
scheduled measurement is not available and the unscheduled/repeated measurement falls 
within the analysis visit windows as described in Table 1, Table 2, and Table 3.
Otherwise, visits will be analyzed as scheduled.
6.1.6. Pooling of Sites
Safety and efficacy data will be pooled across all sites. Additionally, subgroup analyses 
will be performed in which safety, efficacy, and CSHQ endpoints are analyzed by site. See 
Section 8 and Section 9 for more details.
6.1.7. Derived Variables
ADHD-RS-5 Inattention Subscale Score = summed severity and frequency ratings 
of the 9 item inattentiveness ADHD rating sub scale. Each item is scored from a
range of 0 (reflecting no symptoms or a frequency of never or rarely) to 3 (reflecting 
severe symptoms or a frequency of very often), so that the subscale score ranges
from 0 to 27.
ADHD-RS-5 Hyperactivity/Impulsivity Subscale Score = summed severity and 
frequency ratings of the 9 item hyperactivity/impulsivity ADHD rating subscale. 
Each item is scored from a range of 0 (reflecting no symptoms or a frequency of 
never or rarely) to 3 (reflecting severe symptoms or a frequency of very often), so 
that the subscale score ranges from 0 to 27.
ADHD-RS-5 Total Score = summed severity and frequency ratings of the 18 item 
ADHD rating scale based on Diagnostic and Statistical Manual of Mental
Disorders, 5th edition (DSM-5) 4criteria. Each item/symptom is scored from a range 
of 0 (reflecting no symptoms or a frequency of never or rarely) to 3 (reflecting 
severe symptoms or a frequency of very often), so that the total ADHD-RS-5 scores 
range from 0 to 54.
Total Sleep Disturbance Score = summed frequency ratings of the 33-item 
modified, abbreviated CSHQ used to assess examine sleep behavior in small 
children5, 6. Items are rated on a 3-point scale of “Usually,” “Sometimes,” and “Rarely” 
for occurrences in the following sleep domains: bedtime resistance, sleep onset delay, 
sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing,
and daytime sleepiness.
Change from baseline = value at current time point – value at baseline
Percent change from baseline = (change from baseline / baseline) * 100. If both 
baseline and change from baseline are 0 then percent change from baseline will be 
set to 0.


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TEAE = any adverse event (AE) with an onset date/time between the initiation of 
study drug and 5 days after the last dose of study drug. This will include any AE 
with onset prior to initiation of study drug and increased severity after the treatment 
administration.
Treatment duration (days) = LASTDAY – FIRSTDAY + 1 day
where
LASTDAY is the date of last dose, and
FIRSTDAY is the date of first dose.
Mean daily dose = sum of all doses taken (in mg) / total number of days from day 
after previous visit to current visit
BMI = weight (kg) / [(height (cm)/100) * (height (cm)/100)]
Body surface area (BSA) = [height(cm)
weight(kg)]/3600)
Treatment compliance = Number of pills taken/Total number of days on the study
Acceptable Compliance is defined as 80-100% (inclusive) of the total pills to be taken 
on study (eg, 288-360 pills if the subject completes the study).
Fridericia’s correction (QTcF) will be derived as follows:
=
where
Relative rate: RR = 60 / HR 
HR = Heart rate obtained from the ECG.
6.1.8. Data Adjustments/Handling/Conventions
All collected data will be presented in listings. Data not subject to analysis according to 
this plan will not appear in any tables or graphs but will be included only in the data listings.
All P values will be displayed in 4 decimals and rounded using standard scientific notation
(eg, 0.XXXX). If a P value less than 0.0001 occurs it will be shown in tables as <0.0001.
All AEs and medical histories will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) version 20.1 thesaurus or higher. Prior and concomitant 
medications will be coded using the World Health Organization-Drug Dictionary 
Enhanced (WHO-DDE) version September 2017 or higher.
A treatment related AE is any AE with a relationship to the study drug of possibly, 
probably, or definitely related.


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If partial AE or medication dates occur, the convention for replacing missing dates for the 
purpose of statistical analysis is as follows: 
For partial AE and medication start dates:
If the year is unknown, then do not impute the date but assign a missing value.
If the year is known, but the month or month and day is unknown, then:
o
If the year matches the year of first dose date and the end date (if present) 
is after first dose date, then impute as the month and day of the first dose 
date.
o
Otherwise, assign 01 January.
If the year and month are known, but the day is unknown, then:
o
If the month and year match the month and year of the first dose date, then 
impute as the day of the first dose date.
o
Otherwise, assign 01.
For partial AE and medication end dates:
If the year is unknown, then do not impute the date but assign as missing value.
If the year is known, but the month or month and day is unknown, then:
o
If the year matches the year of the last date of the study (date of last 
contact if subject lost to follow-up; date of completion or early termination 
otherwise), then impute as the month and day of the last date of the study.
o
Otherwise, assign 31 December.
If the year and month are known, but the day is unknown, then:
o
If the month and year match the month and year of the last date of the 
study, then impute as the day of the last date of the study.
o
Otherwise, assign the last day of the month.
7.
Study Subjects and Demographics
7.1.
Disposition of Subjects and Withdrawals
Disposition will include an accounting of the number of subjects enrolled into each 
treatment, the number of roll-over subjects who participated in KP415.E01, the number 
of subjects who received treatment, reasons for discontinuation from the study, and 
number of subjects in each analysis population. For each main reason for early 
discontinuation, an assessment will be made to determine when in the course of treatment 
most subjects discontinued early. The last dose received prior to discontinuation will be 
listed.


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The number of subjects remaining in the study by visit will also be presented by 
treatment.
Percentages will be based on the number of subjects in the Dose-Optimization Safety 
Population for Visits 2-4 and in the Treatment-Phase Safety Population for Visits 5-18.
Listings of subject disposition and inclusion and exclusion criteria not met will be 
provided.
7.2.
Protocol Violations and Deviations
All protocol deviations will be listed.
7.3.
Demographics and Other Baseline Characteristics
Summary statistics for age, gender, child-bearing potential, ethnicity, race, height, 
weight, BSA, and BMI will be presented.
For the continuous variables, the number of non-missing values and the mean, standard 
deviation, median, minimum and maximum will be tabulated. 
For the categorical variables, the counts and percentages of each value will be tabulated.   
Baseline variables and dose of study drug will also be presented by study status. Study 
status will be categorized as “Completed Study” or “Discontinued Early.” 
The number and percent of subjects reporting various medical histories and prior 
medications, grouped by MedDRA system organ class and preferred term, will be 
tabulated. 
These analyses will be conducted for the Treatment-Phase Safety Population.
Individual subject listings will be presented for ADHD diagnosis and confirmation as 
well as the Mini International Neuropsychiatric Interview for Children and Adolescents 
(MINI-KID).
7.4.
Exposure and Compliance
At Visit 5, subjects will be dispensed an unblinded bottle with 35 capsules of the 
optimized dose of KP415 (either 20 mg, 30 mg or 40 mg capsules). For roll-over subjects 
from Study KP415.E01, the optimized dose as determined in Study KP415.E01 will be 
used. For new subjects, the optimized dose will be determined at the end of the Dose 
Optimization Phase in the current study. 
Subjects will return to the research clinic at Visits 6-16 with unused study drug, and will 
be dispensed a new bottle with 35 capsules of either 20 mg, 30 mg, or 40 mg KP415 
product. Since the Investigator may increase or decrease the dose of KP415 during the 
Treatment Phase, based on individual tolerability and dose response, the capsule 
strengths dispensed at Visit 6 to Visit 16 may be different from the previous visit. 
The number of capsules dispensed and returned will be accounted for by site staff. 
Acceptable compliance is defined as 80-100% (inclusive). The number and percentage of 


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subjects compliant with study treatment will be tabulated.  The total number of doses 
received as well as the mean, standard deviation, minimum, median and maximum doses 
received will be tabulated overall and by visit, beginning with Visit 6, the first visit in 
which study drug is returned.
The mean daily dose of KP415 (mg), the mean daily dose of KP415 by body weight 
(mg/kg), and the mean daily dose of KP415 by body surface area (mg/m2) will be 
calculated by visit, and will be compared over time (percent change from starting dose in 
the Treatment Phase) to show dose changes over the course of the study. The number and 
percent 
also be reported.
Results from the capsule swallowing test will be listed.
8.
Efficacy Analysis
8.1.
Secondary Efficacy Analysis
The secondary efficacy endpoints include changes in ADHD-RS-5, CGI-S, CGI-I, and 
CSHQ.
During the Dose Optimization Phase (new subjects only): 
•
CGI-S will be assessed at each visit (Screening to Visit 5). ADHD-RS-5 will be 
administered at Visits 2 through Visit 5. CGI-I will be assessed at Visits 3, 4, and 
5 (since CGI-I is an ADHD improvement assessment, it will not be assessed at 
Screening or at Visit 2). 
During the Treatment Phase (all subjects): 
•
ADHD-RS-5, CSHQ, and CGI-S will be assessed at each visit (Visit 5 to Visit 
17, EOT). 
Changes in ADHD-RS-5, CGI-S, and CSHQ will be analyzed in the Efficacy Population. 
Changes in CGI-I will be analyzed in the Efficacy Population during the Dose
Optimization Phase. Change in mean scores between baseline and subsequent study visits 
will be analyzed using a 2-sided paired t-test at a significance level of 0.05. Summary 
statistics and the 95% confidence interval of the mean will be presented as will the 
change from baseline and percent change from baseline. Normality assumptions will be 
tested separately on all evaluable ADHD-RS-5 and CSHQ data across all dose groups 
using the Shapiro-Wilk and Anderson-Darling methods. If both P values for the 
normality tests are >0.01, the data for that particular outcome will be considered normally 
distributed. Otherwise, if one or both P
01, the data for that particular 
outcome will be considered non-normal and then the null hypothesis that the median 
change from baseline is 0 will be tested with the Wilcoxon signed rank test. 
Change from baseline and percent change from baseline will be summarized by overall 
subjects. The analyses will be repeated in the Dose-Optimization Safety population for 
new subjects. No statistical inference will be performed for this analysis population.
Categorical CGI-S and CGI-I results will be summarized by study visit.


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Section 6.1.7 describes the derivations of the above variables and their baseline values.
Subgroup analyses will be performed for the Treatment Phase by gender, age, duration of 
treatment, race, study site, previous stimulant exposure and treatment. Mean and SD 
change from baseline ADHD-RS-5 /CSHQ score for each subgroup will be displayed for 
each visit. Duration of treatment and age will be broken up into quartiles. If the 
distribution of duration of treatment or age is such that the use of quartiles does not lead 
to distinct intervals of values, other cut points will be examined (e.g. tertiles, 
above/below median). CGI-S results will also be presented for the above subgroups.
9.
Safety and Tolerability Analysis
Safety will be evaluated from reported AEs, physical exam results, and changes in the 
following: clinical laboratory values, vital signs, height, weight, BMI, ECG, and C-SSRS 
scores.
Descriptive statistics will be calculated for quantitative safety data and frequency counts
and percentages will be compiled for classification of qualitative safety data. Individual 
subject listings will be prepared for all safety data.
The primary safety analyses will be performed on the Treatment-Phase Safety Population.
Data from the Dose-Optimization Safety Population will be summarized descriptively. All 
safety data will be presented in the listings.
9.1.
Adverse Events
Adverse events with new onset during the study between the initiation of study drug and 5 
days after the last dose of study drug will be considered as TEAEs. This will include any 
AE with onset prior to initiation of study drug and increased severity after the treatment 
initiation. For AEs occurring on the date of the first dose of study drug, if the time of onset 
is missing, the AE will be assumed to be treatment emergent.
All AEs, TEAEs, and SAEs will be coded using MedDRA version 20.1 or higher.
The causal relationship of the AE to the study drug is determined by the investigator as 
Unrelated, Possibly Related, Probably Related, and Definitely Related. These can be 
mapped to Unrelated (Unrelated) and Related (Possibly Related, Probably Related, and 
Definitely Related). 
Adverse event severity grades are reported on a 5-point scale of Grade 1 (Mild), Grade 2 
(Moderate), Grade 3 (Severe), Grade 4 (Life-threatening consequences), or Grade 5 
(Death related to AE). 
The number and percentage of subjects who experience a TEAE along with the 95% 
Wilson confidence interval (CI) will be presented. 
Summaries of incidence rates (frequencies and percentages) of individual TEAEs will be 
summarized by MedDRA system organ class (SOC) and preferred term (PT) for overall 


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subjects and by average dose. This will include overall incidence rates (regardless of 
severity and relationship to study drug). Such summaries will also be displayed for 
TEAEs by maximum severity and relationship to study drug. If a particular event is 
missing the severity and/or relationship, then the severity or relationship will be 
presented as missing.
Each subject will be counted only once within each SOC and PT. If a subject experiences 
more than 1 TEAE within a particular SOC and PT, the TEAE with the strongest 
relationship or the maximum severity, as appropriate, will be included in the summaries 
of relationship and severity.
Incidences will be presented by descending frequency of SOC and PT within SOC, and 
then alphabetically within PT where the incidence is the same; this is based on overall 
subjects.
Missing and partially missing AE start and/or stop dates will be imputed, for the purpose 
of statistical analysis, according to the specifications described in Section 6.1.8.
In the AE data listings, all AEs will be displayed. Any AEs that are treatment emergent 
will be flagged.
Subgroup analyses of safety will be performed by gender, age, duration of treatment, 
race, study site, previous stimulant exposure, and treatment. Duration of treatment and 
age will be broken up into quartiles. If the distribution of duration of treatment or age is 
such that the use of quartiles does not lead to distinct intervals of values, other cut points 
will be examined (e.g. tertiles, above/below median). Subgroup analyses will be 
performed on the Treatment-Phase Safety Population.
9.1.1. Adverse Events Leading to Withdrawal
A summary of incidence rates (frequencies and percentages) of TEAEs leading to 
discontinuation of study drug, by average dose, SOC, and PT will be prepared for the 
Treatment-Phase Safety Population. No inferential statistical tests will be performed.
A data listing of AEs leading to withdrawal of study drug will also be provided, 
displaying details of the event(s) captured on the CRF.
9.1.2. Deaths and Serious Adverse Events
Any deaths that occured during the study will be listed.
Serious adverse events will be listed and also tabulated by SOC and PT and presented by 
treatment.
9.1.3. Other Significant Adverse Events
In accordance with the 2017 FDA Guidance for Industry7, Assessment of Abuse Potential 
of Drugs8, abuse-related AEs will be analyzed in the Treatment Phase using the following 
MedDRA Preferred Terms:


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Euphoria-related terms: Euphoric mood; Elevated mood; Feeling abnormal; 
Feeling drunk; Feeling of relaxation; Dizziness; Thinking abnormal; 
Hallucination; Inappropriate affect
Terms of altered attention, cognition and mood: Somnolence; Mood disorders 
and disturbances
Dissociative/psychotic terms: psychosis; aggression; confusion and disorientation
Related terms not captured elsewhere: drug tolerance; habituation; drug 
withdrawal syndrome; substance-related disorders.
The number and percentage of subjects with at least 1 abuse-related AE will be 
presented. Abuse-related AEs will be categorized by SOC and PT and tabulated by 
treatment, age, and gender. Age will be broken up into quartiles. If the distribution of age
is such that the use of quartiles does not lead to distinct intervals of values, other cut 
points will be examined (e.g. tertiles, above/below median).
Abuse-related AEs will be flagged in the individual subject listings to show the incident 
that led to the AEs, the time at which AEs appear following drug administration, the 
duration of the AEs, and which AEs overlap temporally.
9.2.
Clinical Laboratory Evaluations
Safety clinical hematology laboratory evaluations will include measures of red blood cell 
count, white blood cell count with differential (neutrophils, lymphocytes, monocytes, 
eosinophils, basophils), hemoglobin, hematocrit and platelets, Prothrombin Time (PT) 
and Partial Thromboplastin Time (PTT). 
Serum chemistry laboratory evaluations will include measures of aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), albumin, alkaline phosphatase, 
bicarbonate, total bilirubin, blood urea nitrogen, phosphorus (inorganic) calcium, 
chloride, creatinine phosphokinase, creatinine, gamma glutamyl transferase, glucose, 
lactate dehydrogenase, potassium, sodium, total protein, thyroid stimulating hormone 
(TSH), and uric acid. TSH will be measured at Screening only, for new subjects only who 
did not previously participate in Study KP415.E01.
Urinalysis will include microanalysis for specific gravity, pH, protein, glucose, ketones, 
blood, nitrites, and leukocytes. 
Safety laboratory tests will be summarized as observed values and by post-treatment 
change from baseline for each of the parameters using descriptive statistics overall at each 
visit. Categorical urinalysis results will be summarized using frequencies by visit. Shifts 
from baseline for clinical laboratory values below, within, or above the normal range will 
be provided for hematology, chemistry, and urinalysis results by visit and treatment. See 
Section 6.1.1 for the definition of baseline.
Subjects with significant laboratory abnormalities will be identified in data listings. If any 
laboratory tests are collected at an unscheduled visit post-baseline, the results will be 
included in listings.
Pregnancy test results and urine screens for alcohol and drugs of abuse will be listed.


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9.3.
Vital Signs
Descriptive summaries of observed values and change from baseline will be calculated 
for systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and oral
temperature by visit and average dose.
Weight, height, BMI, and BSA will be summarized by observed values and by post-
treatment change from baseline by visit and treatment. 
9.4.
Electrocardiograms
A 12-lead ECG will be obtained after the subject has been in a supine position for a 
minimum of 3 minutes. Abnormal ECGs may be repeated for confirmation in which case 
only the repeated ECG will be recorded. The QT interval corrected for heart rate will be 
calculated with Fridericia’s formula (QTcF). ECGs will be obtained at Screening, after 
approximately 6 months of treatment (Visit 11), after the last dose of study drug (Visit 
17, EOT), and at Early Termination (if possible). ECG recordings will be evaluated by 
skilled readers operating from a centralized ECG laboratory.
The number and percentage of subjects with normal, abnormal clinically significant, and 
abnormal not clinical significant ECG results will be summarized for the Treatment-
Phase Safety Population by visit.
9.5.
Further Safety Evaluations
Suicidal ideation will be assessed by the C-SSRS, Pediatric Version9. The “Children’s 
Baseline/Screening” version will be assessed at Screening, and the “Children’s Since Last 
Visit” version will be assessed at all visits of the Dose Optimization Phase (new subjects 
only), at all of the Treatment Phase visits, and at Follow-Up or Early Termination. For 
the continuous suicidal ideation, intensity of ideation, and suicidal behavior variables, the 
number of non-missing values and the mean, standard deviation, minimum, median and 
maximum will be tabulated by dose and visit. For the categorical variables, the counts 
and percentages of each value will be tabulated by dose and visit.
A complete physical examination will be completed at Screening, after approximately 6 
months of treatment (Visit 11), after the last dose of study drug (Visit 17, EOT), and at 
Early Termination (if possible). The following body systems will be assessed: general 
appearance, skin, head, neck, eyes, ears, nose, mouth, and throat (HEENT), lymph nodes, 
thyroid, musculoskeletal/extremities, cardiovascular system, lungs, abdomen and a brief 
examination of the neurological system. Physical examination findings will be presented 
in individual subject listings.
9.6.
Concomitant Medication
Summaries of medications that were started prior to dosing and continuing at the time of 
dosing as well as medications that were starting during dosing or during follow up will be 
presented using counts and percentages by WHO Drug Anatomical Therapeutic Chemical 


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(ATC) codes level 4 and level 5 (PT) and treatment for subjects in the Treatment-Phase 
Safety population.
Individual subject listings will be presented for all concomitant medications, lifetime 
history of ADHD treatment, and ADHD medication washout.
10.
Changes from Planned Analysis
Not Applicable
11.
Other Planned Analysis
Not Applicable


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12.
References
1. US Federal Register. (1998) International Conference on Harmonization; Guidance 
on Statistical Principles for Clinical Trials. Department of Health and Human 
Services: Food and Drug Administration [Docket No. 97D-0174]. Federal Register 
Volume 63, Number 179, pages 49583-49598. September 16, 1998.
2. ASA. (2016) Ethical Guidelines for Statistical Practice. Prepared by the Committee 
on Professional Ethics, April 2016. 
http://www.amstat.org/about/ethicalguidelines.cfm
3. RSS. (2014) The Royal Statistical Society: Code of Conduct, 2014. 
http://www.rss.org.uk/Images/PDF/join-us/RSS-Code-of-Conduct-2014.pdf.
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental 
Disorders, Fifth Edition (DSM-5). Arlington, VA, American Psychiatric Association, 
2013.
5. Owens JA, Spirito A, McGuinn M. The Children’s Sleep Habits Questionnaire (CSHQ): 
psychometric properties of a survey instrument for school-aged children. Sleep, 2000a; 
23(8):1043–51.
6. Owens J, Spirito A, McGuinn M, Nobile C. Sleep habits and sleep disturbance in school-
aged children. Journal of Developmental and Behavioral Pediatrics, 2000b; 21(1):27-36.
7. Food and Drug Administration, Assessment of Abuse Potential of Drugs. (2017, 
January). Guidance for Industry, U.S. Department of Health and Human Services, Center 
for Drug Evaluation and Research, Washington, DC.
8. Sellers EM, Romach MK. Categorization of Abuse Potential-Related Adverse Events. 
Clin Pharmacol Drug Dev. 2017 Oct 11. doi: 10.1002/cpdd.394. [Epub ahead of print].
9. Posner K, Brent D, Lucas C, Gould M, Stanley B, Brown G, Fisher P, Zelazny J, Burke 
A, Oquendo M, Mann J. Columbia-Suicide Severity Rating Scale (C-SSRS) Pediatric 
Baseline Version. New York, NY: The Research Foundation for Mental Hygiene, Inc., 
2010.
13.
Tables, Listings, and Figures
All listings, tables, and graphs will have a header showing the sponsor company name 
and protocol and a footer showing the version of SAS, the file name and path, and the 
source of the data (CRF page or listing number).
13.1.
Planned Table Descriptions
The following are planned summary tables for protocol number KP415.S01. The table 
numbers and page numbers are place holders only and will be determined when the tables 
are produced.


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Table 4: Demographic Data Summary Tables and Figures
Number
Population
Title
Table 14.1.1
All Subjects
Summary of Subject Disposition by Treatment 
Table 14.1.2
All Subjects
Summary of Subject Attrition by Treatment
Table 14.1.3.1
Treatment-
Phase Safety
Summary of Demographics and Baseline Characteristics by 
Treatment 
Table 14.1.3.2
Treatment-
Phase Safety
Summary of Demographics and Baseline Characteristics by 
Treatment and Study Status
Table 14.1.4
Treatment-
Phase Safety
Incidence of Medical Histories by SOC, PT, and Treatment
Table 14.1.5.1
Treatment-
Phase Safety
Summary of Prior Medications by ATC Class Level 4, PT, and 
Treatment
Table 14.1.6.1
Treatment-
Phase Safety
Summary of Study Drug Compliance by Treatment and Visit
Table 14.1.6.2
Treatment-
Phase Safety
Summary of Mean Daily Doses by Visit 
Table 14.1.6.3
Treatment-
Phase Safety
Summary of Missed Doses by Treatment
13.2.
Efficacy Data 
Table 5: Efficacy Data
Number
Population
Title
Table 14.2.1.1.1
Efficacy
Summary of ADHD-RS-5 Scores by Study Visit
Table 14.2.1.1.2
Efficacy
Summary of ADHD-RS-5 Scores by Study Visit Using Imputation
Table 14.2.1.1.3
Efficacy
Summary of ADHD-RS-5 Scores by Study Visit and Gender
Table 14.2.1.1.4
Efficacy
Summary of ADHD-RS-5 Scores by Study Visit and Age
Table 14.2.1.1.5
Efficacy
Summary of ADHD-RS-5 Scores by Study Visit and Duration of 
Treatment
Table 14.2.1.1.6
Efficacy
Summary of ADHD-RS-5 Scores by Study Visit and Race
Table 14.2.1.1.7
Efficacy
Summary of ADHD-RS-5 Scores by Study Visit and Site
Table 14.2.1.1.8
Efficacy
Summary of ADHD-RS-5 Scores by Study Visit and Previous Stimulant 
Exposure
Table 14.2.1.1.9
Efficacy
Summary of ADHD-RS-5 Scores by Study Visit and Treatment
Table 14.2.1.2.1
Efficacy
Summary of CGI-S by Study Visit
Table 14.2.1.2.2
Efficacy
Summary of CGI-S by Study Visit and Gender
Table 14.2.1.2.3
Efficacy
Summary of CGI-S by Study Visit and Age


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Number
Population
Title
Table 14.2.1.2.4
Efficacy
Summary of CGI-S by Study Visit and Duration of Treatment
Table 14.2.1.2.5
Efficacy
Summary of CGI-S by Study Visit and Race
Table 14.2.1.2.6
Efficacy
Summary of CGI-S by Study Visit and Site
Table 14.2.1.2.7
Efficacy
Summary of CGI-S by Study Visit and Previous Stimulant Exposure
Table 14.2.1.2.8
Efficacy
Summary of CGI-S by Study Visit and Treatment
Table 14.2.1.3.1
Efficacy
Summary of CGI-I by Study Visit
Table 14.2.1.4.1
Efficacy
Summary of CSHQ Total Sleep Disturbance Score by Study Visit
Table 14.2.1.4.2
Efficacy
Summary of CSHQ Total Sleep Disturbance Score by Study Visit Using 
Imputation
Table 14.2.1.4.3
Efficacy
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and 
Gender
Table 14.2.1.4.4
Efficacy
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and 
Age
Table 14.2.1.4.5
Efficacy
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and 
Duration of Treatment
Table 14.2.1.4.6
Efficacy
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and 
Race
Table 14.2.1.4.7
Efficacy
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and 
Site
Table 14.2.1.4.8
Efficacy
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and 
Previous Stimulant Exposure
Table 14.2.1.4.9
Efficacy
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and 
Treatment


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13.3.
Safety Data
Table 6: Safety Data
Number
Population
Title
14.3.1 Displays of Adverse Events
Table 14.3.1.1.1
Treatment-Phase 
Safety
Summary of Treatment Emergent Adverse Events by Treatment 
Table 14.3.1.1.2
Dose-
Optimization 
Safety
Summary of Treatment Emergent Adverse Events by Treatment 
Table 14.3.1.2.1
Treatment-Phase 
Safety
Incidence of Treatment Emergent Adverse Events by SOC, PT, and 
Treatment
Table 14.3.1.2.2
Dose-
Optimization 
Safety
Incidence of Treatment Emergent Adverse Events by SOC, PT, and 
Treatment
Table 14.3.1.3.1
Treatment-Phase 
Safety
Incidence of Treatment Emergent Adverse Events by Maximum 
Severity, SOC, PT, and Treatment
Table 14.3.1.3.2
Dose-
Optimization 
Safety
Incidence of Treatment Emergent Adverse Events by Maximum 
Severity, SOC, PT, and Treatment
Table 14.3.1.3.3
Treatment-Phase 
Safety
Incidence of Treatment Emergent Adverse Events by Maximum 
Severity, SOC, PT, and Gender
Table 14.3.1.3.4
Treatment-Phase 
Safety
Incidence of Treatment Emergent Adverse Events by Maximum 
Severity, SOC, PT, and Age
Table 14.3.1.3.5
Treatment-Phase 
Safety
Incidence of Treatment Emergent Adverse Events by Maximum 
Severity, SOC, PT, and Duration of Treatment
Table 14.3.1.3.6
Treatment-Phase 
Safety
Incidence of Treatment Emergent Adverse Events by Maximum 
Severity, SOC, PT, and Race
Table 14.3.1.3.7
Treatment-Phase 
Safety
Incidence of Treatment Emergent Adverse Events by Maximum 
Severity, SOC, PT, and Site
Table 14.3.1.3.8
Treatment-Phase 
Safety
Incidence of Treatment Emergent Adverse Events by Maximum 
Severity, SOC, PT, and Previous Stimulant Exposure
Table 14.3.1.4.1
Treatment-Phase 
Safety
Incidence of Treatment Related Treatment Emergent Adverse Events by 
SOC, PT, and Treatment
Table 14.3.1.4.2
Dose-
Opimization 
Safety
Incidence of Treatment Related Treatment Emergent Adverse Events by 
SOC, PT, and Treatment
Table 14.3.1.5.1
Treatment-Phase 
Safety
Incidence of Treatment Emergent Adverse Events Leading to Study 
Drug Discontinuation by SOC, PT, and Treatment


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Number
Population
Title
Table 14.3.1.5.2
Dose-
Optimization 
Safety
Incidence of Treatment Emergent Adverse Events Leading to Study 
Drug Discontinuation by SOC, PT, and Treatment
14.3.2 Summary of Deaths, Other Serious and Significant Adverse Events
Table 14.3.2.1
Treatment-Phase 
Safety
Incidence of Serious Adverse Events by SOC, PT, and Treatment, 
Table 14.3.2.2
Dose-
Optimization 
Safety
Incidence of Serious Adverse Events by SOC, PT, and Treatment
14.3.3 Narratives of Deaths, Other Serious and Certain Other Significant Adverse Events
Table 14.3.3.1.1
Treatment-Phase 
Safety
Listing of Adverse Events Leading to Study Drug Discontinuation
Table 14.3.3.1.2
Dose-
Optimization 
Safety
Listing of Adverse Events Leading to Study Drug Discontinuation
Table 14.3.3.2.1
Treatment-Phase 
Safety
Listing of Serious Adverse Events
Table 14.3.3.2.2
Dose-
Optimization 
Safety
Listing of Serious Adverse Events
Table 14.3.3.3.1
Treatment-Phase 
Safety
Listing of Deaths
Table 14.3.3.3.2
Dose-
Optimization 
Safety
Listing of Deaths
Table 14.3.3.4.1
Treatment-Phase 
Safety
Incidence of Abuse Related Adverse Events by SOC, PT, and Treatment
Table 14.3.3.4.2
Treatment-Phase 
Safety
Incidence of Abuse Related Adverse Events by SOC, PT, and Age
Table 14.3.3.4.3
Treatment-Phase 
Safety
Incidence of Abuse Related Adverse Events by SOC, PT, and Gender
Table 14.3.3.4.4
Dose-
Optimization 
Safety
Incidence of Abuse Related Adverse Events by SOC, PT, and Treatment
14.3.4 Abnormal Laboratory Value 
NA
14.3.5 Laboratory Data Summary Tables
Table 14.3.5.1.1
Treatment-Phase 
Safety
Summary of Hematology Laboratory Results by Study Visit and
Treatment


Statistical Analysis Plan, 
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Number
Population
Title
Table 14.3.5.1.2
Treatment-Phase 
Safety
Shift from Baseline in Hematology Laboratory Results by Study Visit
and Treatment
Table 14.3.5.2.1
Treatment-Phase 
Safety
Summary of Serum Chemistry Laboratory Results by Study Visit and 
Treatment
Table 14.3.5.2.2
Treatment-Phase 
Safety
Shift from Baseline in Serum Chemistry Laboratory Results by Study 
Visit and Treatment
Table 14.3.5.3.1
Treatment-Phase 
Safety
Shift from Baseline in Quantitative Urinalysis Laboratory Results by 
Study Visit and Treatment
Table 14.3.5.3.2
Treatment-Phase 
Safety
Shift from Baseline in Quantitative Urinalysis Laboratory Results by 
Study Visit and Treatment
Table 14.3.5.3.3
Treatment-Phase 
Safety
Summary of Qualitative Urinalysis Laboratory Results by Study Visit
and Treatment
14.3.6 Other Safety Data Summary Tables
Table 14.3.6.1
Treatment-Phase 
Safety
Summary of Vital Signs by Study Visit, and Treatment
Table 14.3.6.2.1
Treatment-Phase 
Safety
Summary of 12-Lead Electrocardiogram by Study Visit and Treatment
Table 14.3.6.2.2
Treatment-Phase 
Safety
Summary of 12-Lead Electrocardiogram Interpretation by Study Visit
and Treatment
Table 14.3.6.3
Treatment-Phase 
Safety
Summary of Columbia-Suicide Severity Rating Scale (C-SSRS)
Table 14.3.6.4
Treatment-Phase 
Safety
Summary of Concomitant Medications by ATC Class Level 4, PT, and 
Treatment


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13.4.
Other Data Summary Tables
13.5.
Planned Listing Descriptions
The following are planned data and patient/subject data listings for protocol number
KP415.S01.
In general, one listing will be produced per CRF domain. All listings will be sorted by 
treatment, site, and subject number. All calculated variables will be included in the 
listings.
In all listings a blank line will be placed between each subject. Within a data listing, if an 
item appears line after line (eg, repetition of subject number), then only the first 
occurrence will be displayed.
In data listings, the information for one subject will be kept on one page if at all possible, 
rather than splitting a subject’s information across pages.
Table 7: Planned Listings
Number
Population
Title / Summary
16.2.1 Subject Discontinuations/Completions
Listing 16.2.1
All Subjects
Subject Disposition
16.2.2 Protocol Deviations
Listing 16.2.2.1
All Subjects
Inclusion and Exclusion Criteria Not Met
Listing 16.2.2.2
All Subjects
Protocol Deviations
16.2.3 Subjects Excluded from the Efficacy Analyses
Listing 16.2.3
All Subjects
Analysis Populations
16.2.4 Demographic Data and Other Baseline Characteristics
Listing 16.2.4.1
All Subjects
Demographics and Baseline Information
Listing 16.2.4.2
All Subjects
Medical History
Listing 16.2.4.3
All Subjects
ADHD Diagnosis and Confirmation
Listing 16.2.4.4
All Subjects
Mini International Neuropsychiatric Interview for Children and 
Adolescents (MINI-KID)
16.2.5 Compliance and/or Drug Concentration Data
Listing 16.2.5.1
All Subjects
Capsule Swallowing Test
Listing 16.2.5.2
All Subjects
Study Drug Dispensation and Return
16.2.6 Individual Efficacy Response Data
Listing 16.2.6.1
All Subjects
ADHD-Rating Scale-5
Listing 16.2.6.2
All Subjects
Clinical Global Impression (CGI) – Severity
Listing 16.2.6.3
All Subjects
Clinical Global Impression (CGI) – Improvement


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Number
Population
Title / Summary
Listing 16.2.6.4
All Subjects
Children’s Sleep Habits Questionnaire
16.2.7 Adverse Event Listings (by Subject)
Listing 16.2.7.1
All Subjects
Adverse Events
16.2.8 Laboratory Values and Other Clinical Observations and Measurements (by Subject)
Listing 16.2.8.1.1
All Subjects
Clinical Laboratory Data: Hematology
Listing 16.2.8.1.2
All Subjects
Clinical Laboratory Data: Serum Chemistry
Listing 16.2.8.1.3
All Subjects
Clinical Laboratory Data: Urinalysis
Listing 16.2.8.1.4
All Subjects
Clinical Laboratory Data: Urine Drug Screen and Pregnancy Tests
Listing 16.2.8.2
All Subjects
Vitals Signs
Listing 16.2.8.3
All Subjects
12-Lead Electrocardiogram (ECG)
Listing 16.2.8.4
All Subjects
Columbia-Suicide Severity Rating Scale (C-SSRS)
Listing 16.2.8.5
All Subjects
Physical Examination
Listing 16.2.8.6
All Subjects
Prior and Concomitant Medications
Listing 16.2.8.7
All Subjects
Lifetime History of ADHD Treatment
Listing 16.2.8.8
All Subjects
ADHD Medication Washout


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13.6.
Planned Figure Descriptions
Not Applicable


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Tables, Listings, and Listing Shells
13.7.
Standard Layout for all Tables, Listings, and Figures
The following standard layout will be applied to all Tables, Listings, and Figures in support of this study. Note that programming 
notes may be added if appropriate after each TLF shell.


Statistical Analysis Plan, 
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Protocol Number KP415.S01
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Figure 1: Standardized Layout
KemPharm, Inc.
Page xx of xx
Protocol: KP415.S01
Version
<Table, Listing, Figure> xx.x.x
<Title of Table Listing or Figure>
<Study Population and if applicable subgroup Description>
____________________________________________________________________________________________________________
Body of Table, Listing or Figure
___________________________________________________________________________________________________________
<Note: If directly Applicable>
Footnote 1 <if applicable> Recommendation is to keep footnotes to a minimum
Footnote 2 <if applicable>
Footnote n <if applicable>
Footnote n+1 <pgm path and name>,  <date>


Statistical Analysis Plan, 
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13.8.
Planned Table Shells


Statistical Analysis Plan, 
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Table 14.1.1
Summary of Subject Disposition
All Subjects
Status
KP415
(N=XX)
Enrolled
XX
Study Populations:
Treatment-Phase Safety Population [1]
XX (XX.X%)
Efficacy Population [2]
XX (XX.X%)
Dose-Optimization Safety Population [3]
XX (XX.X%)
Completed Study
XX (XX.X%)
Ongoing in Study
XX (XX.X%)
Prematurely Discontinued from Study
XX (XX.X%)
Reason for Discontinuation:
      Subject withdrawal of consent
XX (XX.X%)
      Non-compliance with study procedures
XX (XX.X%)
Adverse event
XX (XX.X%)
Lack of efficacy
XX (XX.X%)
      Protocol deviation
XX (XX.X%)
Lost to follow-up
XX (XX.X%)
Sponsor request for early termination of study
XX (XX.X%)
Positive pregnancy test
XX (XX.X%)
      Out-of-range vital signs
XX (XX.X%)
Sponsor planned study stop
XX (XX.X%)
Other
XX (XX.X%)
Participated in KP415.E01 and enrolled as roll-over subjects
XX (XX.X%)
Participated in KP415.E01 and enrolled as new subjects
XX (XX.X%)
Note: Percentages are n/Number of subjects in enrolled *100. Subjects are summarized overall. 
[1] The Treatment-Phase Safety Population includes all subjects who are enrolled in the Treatment Phase and received at least 1 dose of study medication 
in the Treatment Phase and had at least 1 post-dose safety assessment in the Treatment Phase.
[2] The Efficacy Population includes all enrolled subjects who received at least 30 days of study medication in the Treatment Phase and had adequate data 
to assess the change from baseline of the efficacy parameters and no protocol deviations that could affect the efficacy parameters.
[3] The Dose-Optimization Population includes all subjects who are enrolled in the Dose Optimization Phase and received at least 1 dose of study 
medication in the Dose Optimization Phase and had at least 1 post-dose safety assessment in the Dose Optimization Phase.
SOURCE: Listings 16.2.1, 16.2.3


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Table 14.1.2
Summary of Subject Attrition by Study Phase
All Subjects
Visit Number
KP415
(N=XX)
Screening Phase:
Visit 01A (New Subjects)
XX (XX.X%)
Visit 01B (Rollover Subjects)
XX (XX.X%)
Dose Optimization Phase:
Visit 02 (New Subjects)
XX (XX.X%)
Visit 03 (New Subjects)
XX (XX.X%)
Visit 04 (New Subjects)
XX (XX.X%)
Treatment Phase:
Visit 05 
XX (XX.X%)
Visit 06 
XX (XX.X%)
Visit 07 
XX (XX.X%)
Visit 08 
XX (XX.X%)
Visit 09 
XX (XX.X%)
Visit 10 
XX (XX.X%)
Visit 11 
XX (XX.X%)
Visit 12 
XX (XX.X%)
Visit 13 
XX (XX.X%)
Visit 14 
XX (XX.X%)
Visit 15 
XX (XX.X%)
Visit 16 
XX (XX.X%)
Visit 17 
XX (XX.X%)
Follow up:
Visit 18 
XX (XX.X%)
Note: Percentages are n/Number of subjects in enrolled*100. Subjects are summarized overall.
SOURCE: Listings 16.2.1


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Table 14.1.3.1
Summary of Demographics and Baseline Characteristics
Treatment-Phase Safety Population
Variable
Statistic or Category
KP415
(N=XX)
Age (years)
n
XX
Mean (SD)
XX.X (XX.XX)
CV%
XX.XX
Median
XX.X
Min, Max
XX, XX
Gender
Male
XX (XX.X%)
Female
XX (XX.X%)
Child-Bearing Potential? [1]
Yes
XX (XX.X%)
No
XX (XX.X%)
Ethnicity
Hispanic or Latino
XX (XX.X%)
Not Hispanic or Latino
XX (XX.X%)
Race
American-Indian or Alaska Native
XX (XX.X%)
Asian
XX (XX.X%)
Black or African-American
XX (XX.X%)
Native Hawaiian or Other Pacific Islander
XX (XX.X%)
White
XX (XX.X%)
Other
XX (XX.X%)
More than One Race
XX (XX.X%)
Abbreviations: CV% = coefficient of variation; SD = standard deviation. 
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Subjects are summarized overall.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Treatment-Phase Safety Population. 
SOURCE: Listing 16.2.4.1


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Table 14.1.3.1 (cont.)
Demographics and Baseline Characteristics
Treatment-Phase Safety Population
Variable
Statistic or Category
KP415
(N=XX)
Height (cm)
n
XX
Mean (SD)
XX.X (XX.XX)
CV%
XX.XX
Median
XX.X
Min, Max
XX, XX
Weight (kg)
n
XX
Mean (SD)
XX.X (XX.XX)
CV%
XX.XX
Median
XX.X
Min, Max
XX, XX
Body Surface Area (mg/m2)
n
XX
Mean (SD)
XX.X (XX.XX)
CV%
XX.XX
Median
XX.X
Min, Max
XX, XX
Body Mass Index (kg/m2)
n
XX
Mean (SD)
XX.X (XX.XX)
CV%
XX.XX
Median
XX.X
Min, Max
XX, XX
Abbreivations: CV% = coefficient of variation; SD = standard deviation. 
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Subjects are summarized overall.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Treatment-Phase Safety Population. 
SOURCE: Listing 16.2.4.1


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Table 14.1.3.2 
Demographics and Baseline Characteristics by Study Status
Treatment-Phase Safety Population
(Same Shell as Table 14.1.3.1)
Programming Note: Update Note to read “Percentages are n/Number of subjects in the Treatment-Phase Safety Population for each study status*100.” Add Listing 16.2.3 to 
SOURCE. Add a header row that says “Study Status: XXXX”, where XXXX is “Completed Study” or “Discontinued Early”.


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Table 14.1.4
Incidence of Medical Histories by SOC and PT
Treatment-Phase Safety Population
System Organ Class
Preferred Term
KP415
(N=XX)
Subjects with at least 1 Recorded Medical History
XX (XX.X%)
System Organ Class 1
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
System Organ Class 2
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
Abbreviations: PT = Preferred Term; SOC = System Organ Class. 
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Subjects are summarized overall. Medical histories were coded 
using MedDRA version 20.1. Subjects were counted once for each system organ class (SOC) and once for each preferred term (PT). Medical history terms 
are displayed by descending frequency of SOC, then PT within SOC, and then alphabetically by PT. 
SOURCE: Listing 16.2.4.2
Programming note: SOC & PT text should be in proper case in table, as shown in the shell.


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Table 14.1.5
Summary of Prior Medications by ATC Class Level 4 and PT
Treatment-Phase Safety Population
ATC Class Level 4
Preferred Term (ATC Class Level 5)
KP415
(N=XX)
Subjects with at least 1 Prior Medication
XX (XX.X%)
ATC Class 1
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
ATC Class 2
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
Abbreviations: ATC = Anatomic Therapeutic Chemical; PT = Preferred Term
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Subjects are summarized overall. Medications were coded 
using WHO-DDE version September 2017. Prior medications are all medications that were started before the date of the first dose of study drug in the 
Treatment Phase. Medications are displayed by descending frequency of Anatomic Therapeutic Chemical (ATC) Level 4 classification, by Preferred Term 
(PT) within ATC, and then alphabetically. Subjects were counted only once for each ATC and PT. 
SOURCE: Listing 16.2.9.6
Programming note: ATC & PT text should be in proper case in table, as shown in the shell.


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Table 14.1.6.1 
Summary of Study Drug Compliance by Visit
Treatment-Phase Safety Population
Statistic / Category
KP415
(N=XX)
Compliant [1]
XX (XX.X%)
Not Compliant
XX (XX.X%)
Total Number of Doses Taken
n
XX
Mean (SD)
XX.X (XX.XX)
CV%
XX.XX
Median
XX.X
Min, Max
XX, XX
Total Number of Doses Taken Visit 6
n
XX
Mean (SD)
XX.X (XX.XX)
CV%
XX.XX
Median
XX.X
Min, Max
XX, XX
Total Number of Doses Taken Visit 7
n
XX
Mean (SD)
XX.X (XX.XX)
CV%
XX.XX
Median
XX.X
Min, Max
XX, XX
Continue for Visits 8-17
Abbreviations: CV% = coefficient of variation; SD = Standard Deviation. 
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Subjects are summarized overall. Number of doses 
taken is calculated as the number of expected doses (number of days on study, where number of days on study is derived as last treatment – first 
treatment + 1) minus total number of missed doses, as collected in the CRF.
[1] Subjects were to receive one dose in the morning each day. Acceptable compliance is defined as 80-100% (inclusive) and is derived as number of 
doses taken / number of expected doses * 100%.
SOURCE: Listing 16.2.5.2


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Table 14.1.6.2
Summary of Mean Daily Doses by Visit
Treatment-Phase Safety Population
Mean Daily Dose (mg)
Mean Daily Dose by Body Weight (mg/kg)
Mean Daily Dose by BSA (mg/m2)
Study Visit
(N = XX)
(N = XX)
(N = XX)
Statistic
Observed
CFB
%CFB
Observed
CFB
%CFB
Observed
CFB
%CFB
Visit 5
n
XX
--
--
XX
--
--
XX
--
--
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
CV%
XX.XX
XX.XX
XX.XX
Median
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
Visit 6
n
XX
XX
XX
XX
XX
XX
XX
XX
XX
Mean
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
CV%
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Continue for the the remaining Visits.
Abbreviations: BSA = body surface area; CFB = change from baseline; CV% = coefficient of variation; SD = standard deviation.
Note: Mean daily dose = sum of all doses taken (in mg) / total number of days from the day after the previous visit to current visit.
SOURCE: Listing 16.2.5.2


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Table 14.1.6.3
Summary of Missed Doses by Treatment 
Treatment-Phase Safety Population
Number of Days Study Drug Not Taken [1]
KP415
(N=XX)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Subjects are summarized overall. A subject contributes 
to row if they did not take study drug for the continuous period of specified days.
[1] Subjects were to receive one dose in the morning each day. 
SOURCE: Listing 16.2.5.2


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Table 14.2.1.1.1
Summary of ADHD-RS-5 Scores by Study Visit 
Efficacy Population
Parameter: ADHD-RS-5 Total Score
Study Visit
KP415 
(N=XX)
Statistic
Observed
CFB
%CFB
Baseline [1]
n
XX
XX
XX
     Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
     (95% CI of Mean)
(XX.X, XX.X)
(XX.X, XX.X)
(XX.X, XX.X)
CV%
XX.XX
XX.XX
XX.XX
     Median
XX.X
XX.X
XX.X
     Min, Max
XX, XX
XX, XX
XX, XX
Visit 2
n
XX
XX
XX
     Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
(95% CI of Mean)
(XX.X, XX.X)
(XX.X, XX.X)
(XX.X, XX.X)
CV%
XX.XX
XX.XX
XX.XX
     Median
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
P-value [2]
X.XXXX
Abbreviations: CFB = change from baseline; CV% = coefficient of variation; SD = standard deviation.
Note: ADHD-RS-5 Inattention Subscale Score = summed severity and frequency ratings of the 9 item inattentiveness ADHD rating sub scale. 
ADHD-RS-5 Hyperactivity/Impulsivity Subscale Score = summed severity and frequency ratings of the 9 item hyperactivity/impulsivity ADHD
rating subscale. Each item is scored from a range of 0 (reflecting no symptoms or a frequency of never or rarely) to 3 (reflecting severe 
symptoms or a frequency of very often), so that the subscale scores range from 0 to 27. ADHD-RS-5 Total Score = summed severity and 
frequency ratings of the 18 item ADHD rating scale (Inattention and Hyperactivity/Impulsivity subscales combined). The total ADHD-RS-5
scores range from 0 to 54. A negative change indicates improvement. 95% Wilson CIs are presented.
[1] The baseline is measured before the first dose of study drug at Visit 2 for new subjects and at Visit 5 for roll-over subjects. Visit 3 and Visit 4 
will only be populated for new subjects in the Dose Optimization Phase. Visits 5-17 will include all subjects in the Treatment Phase.
[2] P-value for testing mean change from baseline to subsequent visit is 0 is calculated using a paired t-test.
SOURCE: Listing 16.2.6.1


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
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Page 53 of 123
Table 14.2.1.1.1 (cont.)
Summary of ADHD-RS-5 Scores by Study Visit 
Efficacy Population
Parameter: ADHD-RS-5 Total Score
Study Visit
KP415 
(N=XX)
Statistic
Observed
CFB
%CFB
Visit 4
n
XX
XX
XX
     Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
     (95% CI of Mean)
(XX.X, XX.X)
(XX.X, XX.X)
(XX.X, XX.X)
CV%
XX.XX
XX.XX
XX.XX
     Median
XX.X
XX.X
XX.X
     Min, Max
XX, XX
XX, XX
XX, XX
P-value
X.XXXX
Continue for Study Visits 5-17. Repeat for the following parameters: ADHD-RS-5 Inattention Subscale Score; ADHD-RS-5
Hyperactivity/Impulsivity Subscale Score.
Abbreviations: CFB = change from baseline; CV% = coefficient of variation; SD = standard deviation.
Note: ADHD-RS-5 Inattention Subscale Score = summed severity and frequency ratings of the 9 item inattentiveness ADHD rating sub scale. 
ADHD-RS-5 Hyperactivity/Impulsivity Subscale Score = summed severity and frequency ratings of the 9 item hyperactivity/impulsivity ADHD 
rating subscale. Each item is scored from a range of 0 (reflecting no symptoms or a frequency of never or rarely) to 3 (reflecting severe 
symptoms or a frequency of very often), so that the subscale scores range from 0 to 27. ADHD-RS-5 Total Score = summed severity and 
frequency ratings of the 18 item ADHD rating scale (Inattention and Hyperactivity/Impulsivity subscales combined). The total ADHD-RS-5
scores range from 0 to 54. A negative change indicates improvement. 95% Wilson CIs are presented.
[1] The baseline is measured before the first dose of study drug at Visit 2 for new subjects and at Visit 5 for roll-over subjects. Visit 3 and Visit 4 
will only be populated for new subjects in the Dose Optimization Phase. Visits 5-17 will include all subjects in the Treatment Phase.
[2] P-value for testing mean change from baseline to subsequent visit is 0 is calculated using a paired t-test.
SOURCE: Listing 16.2.6.1
Programming note: Check assumptions for normality per Section 8.1 of the SAP. If normality assumptions are violated, use the Wilcoxon signed rank test and update the footnote 
accordingly.


Statistical Analysis Plan, 
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Table 14.2.1.1.2
Summary of ADHD-RS-5 Scores by Study Visit Using Imputation
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Add the following footnote “Missing scores were inputed using Last Observation Carried Forward (LOCF)”
Table 14.2.1.1.3
Summary of ADHD-RS-5 Scores by Study Visit and Gender
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Each subgroup will have its own set of columns. Add 16.2.4.1 to SOURCE.
Table 14.2.1.1.4
Summary of ADHD-RS-5 Scores by Study Visit and Age
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup.
Check cut points per Section 8.1 of SAP. Add 16.2.4.1 to SOURCE.
Table 14.2.1.1.5
Summary of ADHD-RS-5 Scores by Study Visit and Duration of Treatment
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup.
Check cut points per Section 8.1 of SAP. Add 16.2.5.2 to SOURCE.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
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Page 55 of 123
Table 14.2.1.1.6
Summary of ADHD-RS-5 Scores by Study Visit and Race
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. Add 
16.2.4.1 to SOURCE.
Table 14.2.1.1.7
Summary of ADHD-RS-5 Scores by Study Visit and Site
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. Add 
16.2.1 to SOURCE.
Table 14.2.1.1.8
Summary of ADHD-RS-5 Scores by Study Visit and Previous Stimulant Exposure
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Each subgroup will have its own set of columns (subgroups include Previous Stimulant Exposure and No Stimulant Exposure). Add 16.2.8.6 to SOURCE.
Table 14.2.1.1.9
Summary of ADHD-RS-5 Scores by Study Visit and Treatment
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. Add 
footnote “Treatment groups are based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the 
study during the Treatment Phase, is presented.” Add 16.2.5.2 to SOURCE.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
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Page 56 of 123
Table 14.2.1.2.1
Summary of CGI-S by Study Visit 
Efficacy Population
KP415
(N=XX)
Study Visit
      Statistic
n (%)
95% CI
Screening [1]
XX
0 = Not Assessed
XX (XX.X%)
(XX.X%, XX.X%)
1 = Normal, Not at All Ill
XX (XX.X%)
(XX.X%, XX.X%)
      2 = Borderline Mentally Ill
XX (XX.X%)
(XX.X%, XX.X%)
      3 = Mildly Ill
XX (XX.X%)
(XX.X%, XX.X%)
4 = Moderately Ill
XX (XX.X%)
(XX.X%, XX.X%)
5 = Markedly Ill
XX (XX.X%)
(XX.X%, XX.X%)
     6 = Severely Ill
XX (XX.X%)
(XX.X%, XX.X%)
7 = Among the Most Extremely Ill Patients
XX (XX.X%)
(XX.X%, XX.X%)
Baseline [2]
XX
     0 = Not Assessed
XX (XX.X%)
(XX.X%, XX.X%)
1 = Normal, Not at All Ill
XX (XX.X%)
(XX.X%, XX.X%)
2 = Borderline Mentally Ill
XX (XX.X%)
(XX.X%, XX.X%)
      3 = Mildly Ill
XX (XX.X%)
(XX.X%, XX.X%)
4 = Moderately Ill
XX (XX.X%)
(XX.X%, XX.X%)
5 = Markedly Ill
XX (XX.X%)
(XX.X%, XX.X%)
6 = Severely Ill
XX (XX.X%)
(XX.X%, XX.X%)
7 = Among the Most Extremely Ill Patients
XX (XX.X%)
(XX.X%, XX.X%)
Repeat for Visits 3-17
Abbreviation: CGI-S = Clinical Global Impression – Severity; CI = confidence interval.
Note: Percentages are n/Number of subjects in the Efficacy Population at each visit*100. The CGI-S rates the severity of the 
subject’s illness at the time of assessment, relative to the clinician’s past experience with subjects who have the same 
diagnosis. Subjects are summarized by treatment recieved. 95% Wilson CIs are presented.
[1] Screening will only include new subjects at Visit 01A. 
[2] The baseline is measured before the first dose of study drug at Visit 2 for new subjects and at Visit 5 for roll-over subjects.
Visit 3 and Visit 4 will only be populated for new subjects in the Dose Optimization Phase. Visits 5-17 will include all subjects 
in the Treatment Phase.
SOURCE: Listing 16.2.6.2


Statistical Analysis Plan, 
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Protocol Number KP415.S01
PCN Number KEMP7419
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Table 14.2.1.1.2
Summary of CGI-S by Study Visit by Study Visit and Gender
Efficacy Population
(Same shell as Table 14.2.1.2.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. 
Change SOURCE to Listing 16.2.6.2. Add 16.2.4.1 to SOURCE.
Table 14.2.1.2.3
Summary of CGI-S by Study Visit and Age
Efficacy Population
(Same shell as Table 14.2.1.2.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup.
Check cut points per Section 8.1 of SAP. Change SOURCE to Listing 16.2.6.2. Add 16.2.4.1 to SOURCE.
Table 14.2.1.2.4
Summary of CGI-S by Study Visit and Duration of Treatment
Efficacy Population
(Same shell as Table 14.2.1.2.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup.
Check cut points per Section 8.1 of SAP. Change SOURCE to Listing 16.2.6.2. Add 16.2.5.2 to SOURCE..
Table 14.2.1.2.5
Summary of CGI-S by Study Visit and Race
Efficacy Population
(Same shell as Table 14.2.1.2.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup.
Change SOURCE to Listing 16.2.6.2. Add 16.2.4.1 to SOURCE.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 58 of 123
Table 14.2.1.2.6
Summary of CGI-S by Study Visit and Site
Efficacy Population
(Same shell as Table 14.2.1.2.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup.
Change SOURCE to Listing 16.2.6.2. Add 16.2.1 to SOURCE.
Table 14.2.1.2.7
Summary of CGI-S by Study Visit and Previous Stimulant Exposure
Efficacy Population
(Same shell as Table 14.2.1.2.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. 
Change SOURCE to Listing 16.2.6.2. Add 16.2.8.6 to SOURCE.
Table 14.2.1.2.8
Summary of CGI-S by Study Visit and Treatment
Efficacy Population
(Same shell as Table 14.2.1.2.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. 
Change SOURCE to Listing 16.2.6.2. Add 16.2.5.2 to SOURCE.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
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Page 59 of 123
Table 14.2.1.3.1
Summary of CGI-I by Study Visit 
Efficacy Population
Dose Optimization Phase (New Subjects Only)
KP415
(N=XX)
Study Visit
      Statistic
n (%)
95% CI
Visit 3
XX
0 = Not Assessed
XX (XX.X%)
(XX.X%, XX.X%)
1 = Very Much Improved
XX (XX.X%)
(XX.X%, XX.X%)
      2 = Much Improved
XX (XX.X%)
(XX.X%, XX.X%)
3 = Minimally Improved
XX (XX.X%)
(XX.X%, XX.X%)
4 = No Change
XX (XX.X%)
(XX.X%, XX.X%)
      5 = Minimally Worse
XX (XX.X%)
(XX.X%, XX.X%)
      6 = Much Worse
XX (XX.X%)
(XX.X%, XX.X%)
7 = Very Much Worse
XX (XX.X%)
(XX.X%, XX.X%)
Continue for Visit 4 and Visit 5
Abbreviation: CGI-I = Clinical Global Impression – Improvement; CI = confidence interval.
Note: Percentages are n/Number of subjects in the Efficacy Population at each visit*100. The CGI-I measures the overall improvement 
in the subject’s condition post-treatment. The Investigator will rate the subject’s total improvement whether or not it is due entirely to 
drug treatment. By definition, all CGI-I assessments are evaluated against baseline conditions. Subjects are summarized by treatment 
received. 95% Wilson CIs are presented.
SOURCE: Listing 16.2.6.3


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
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Page 60 of 123
Table 14.2.1.4.1
Summary of CSHQ Total Sleep Disturbance Score by Study Visit 
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Add CSHQ = Children’s Sleep Habits Questionnaire to abbreviations in footnote. Change SOURCE to Listing 16.2.6.4.
Table 14.2.1.4.2
Summary of CSHQ Total Sleep Disturbance Score by Study Visit Using Imputation
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Add CSHQ = Children’s Sleep Habits Questionnaire to abbreviations in footnote. Add the following footnote “Missing scores were inputed using Last Observation 
Carried Forward (LOCF)”. Change SOURCE to Listing 16.2.6.4.
Table 14.2.1.4.3
Summary of CSHQ Total Sleep Disturbance Score by Study Visit by Study Visit and Gender
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Add CSHQ = Children’s Sleep Habits Questionnaire to abbreviations in footnote. Each subgroup will have its own set of columns. If there are too many 
subgroups such that the table would be too wide, repeat the table for each subgroup. Change SOURCE to Listing 16.2.6.4. Add 16.2.4.1 to SOURCE.
Table 14.2.1.4.4
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and Age
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Add CSHQ = Children’s Sleep Habits Questionnaire to abbreviations in footnote. Each subgroup will have its own set of columns. If there are too many 
subgroups such that the table would be too wide, repeat the table for each subgroup. Check cut points per Section 8.1 of SAP. Change SOURCE to Listing 16.2.6.4. Add 16.2.4.1 to 
SOURCE.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
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Page 61 of 123
Table 14.2.1.4.5
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and Duration of Treatment
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Add CSHQ = Children’s Sleep Habits Questionnaire to abbreviations in footnote. Each subgroup will have its own set of columns. If there are too many 
subgroups such that the table would be too wide, repeat the table for each subgroup. Check cut points per Section 8.1 of SAP. Change SOURCE to Listing 16.2.6.4. Add 16.2.5.2 to 
SOURCE..
Table 14.2.1.4.6
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and Race
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Add CSHQ = Children’s Sleep Habits Questionnaire to abbreviations in footnote. Each subgroup will have its own set of columns. If there are too many 
subgroups such that the table would be too wide, repeat the table for each subgroup. Change SOURCE to Listing 16.2.6.4. Add 16.2.4.1 to SOURCE.
Table 14.2.1.4.7
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and Site
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Add CSHQ = Children’s Sleep Habits Questionnaire to abbreviations in footnote. Each subgroup will have its own set of columns. If there are too many 
subgroups such that the table would be too wide, repeat the table for each subgroup. Change SOURCE to Listing 16.2.6.4. Add 16.2.1 to SOURCE.
Table 14.2.1.4.8
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and Previous Stimulant Exposure
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Add CSHQ = Children’s Sleep Habits Questionnaire to abbreviations in footnote. Each subgroup will have its own set of columns. If there are too many 
subgroups such that the table would be too wide, repeat the table for each subgroup. Change SOURCE to Listing 16.2.6.4. Add 16.2.8.6 to SOURCE.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 62 of 123
Table 14.2.1.4.9
Summary of CSHQ Total Sleep Disturbance Score by Study Visit and Treatment
Efficacy Population
(Same shell as Table 14.2.1.1.1)
Programming note: Add CSHQ = Children’s Sleep Habits Questionnaire to abbreviations in footnote. Each subgroup will have its own set of columns. If there are too many 
subgroups such that the table would be too wide, repeat the table for each subgroup. Change SOURCE to Listing 16.2.6.4. Add 16.2.5.2 to SOURCE.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 63 of 123
Table 14.3.1.1.1
Summary of Treatment Emergent Adverse Events by Treatment
Treatment-Phase Safety Population
KP415
20 mg
30 mg
40 mg
Overall
(N=XX)
(N=XX)
(N=XX)
(N=XX)
Category
n (%)
n (%)
n (%)
n (%)
95% CI
Subjects with at least 1 TEAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Maximum Severity of TEAE 
      Grade 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
      Grade 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Grade 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Grade 4
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
      Grade 5
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Subjects with a Related TEAE [2]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Subjects with a TEAE Leading to Discontinuation of 
Study Drug
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Subjects with an SAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Subjects with an AE leading to Death
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abbreviations: CI = confidence interval; CRF = Case Report Form; TEAE = Treatment emergent adverse event; SAE = Serious adverse event.
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Treatment groups are based on treatment received. The dose received at the 
beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during the Treatment Phase, is presented. AEs were coded using 
MedDRA version 20.1. A TEAE is any AE with an onset date/time between the initiation of study drug and 5 days after the last dose of study drug. This will include any AE 
with onset prior to initiation of study drug and increased severity after the treatment administration. 95% Wilson CIs are presented.
[1] Related TEAEs are those marked as Possibly Related, Probably Related, or Definitely Related on the CRF.
SOURCE: Listing 16.2.7.1
Programming note: Ensure correct MedDRA version is printed in footnote. Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment 
Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, this should be mentioned in the footnote as “Subject 
XXXXXX was down titrated due to tolerability issues.”; add “16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
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Page 64 of 123
Table 14.3.1.1.2
Summary of Treatment Emergent Adverse Events by Treatment
Dose-Optimization Safety Population
Programming Note: Update footnote with Dose-Optimization Safety Population. Since treatment groups presented are based on the optimized dose (mg) from the Dose Optimization 
Phase, actual doses need to be determined from the data. Update footnote to read “Treatment groups are based on treatment received. The optimized dose is presented.”


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
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Page 65 of 123
Table 14.3.1.2.1
Incidence of Treatment Emergent Adverse Events by SOC, PT, and Treatment
Treatment-Phase Safety Population
KP415
20 mg
30 mg
40 mg
Overall
(N=XX)
System Organ Class
(N=XX)
(N=XX)
(N=XX)
Preferred Term
n (%)
n (%)
n (%)
n (%)
95% CI
Subjects with at least 1 TEAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
System Organ Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
System Organ Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abbreviations: CI = confidence interval; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment emergent adverse event.
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Treatment groups are based on treatment received. The dose received at the 
beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during the Treatment Phase, is presented. AEs were coded using MedDRA 
version 20.1. A TEAE is any AE with an onset date/time between the initiation of study drug and 5 days after the last dose of study drug. This will include any AE with onset prior to 
initiation of study drug and increased severity after the treatment administration. Subjects are counted once for each SOC and once for each PT. AEs are displayed by descending
frequency of SOC, then PT within SOC, and then alphabetically by PT. 95% Wilson CIs are presented.
SOURCE: Listing 16.2.7.1
Programming note: SOC & PT text should be in proper case in table, as shown in the shell. Ensure correct MedDRA version is printed in footnote. Since treatment groups presented 
are based on the dose (mg) received at the beginning of the treatment-phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due 
to tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add “16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 66 of 123
Table 14.3.1.2.2
Incidence of Treatment Emergent Adverse Events by SOC, PT, and Treatment
Dose-Optimization Safety Population
(Same Shell as Table 14.3.1.2.1)
Programming note: Update footnote with Dose-Optimization Safety Population. Since treatment groups presented are based on the optimized dose (mg) from the Dose Optimization 
Phase, actual doses need to be determined from the data. Update footnote to read “Treatment groups are based on treatment received. The optimized dose is presented.”


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 67 of 123
Table 14.3.1.3.1
Incidence of Treatment Emergent Adverse Events by Maximum Severity, SOC, PT, and Treatment
Treatment-Phase Safety Population
KP415
System Organ Class
Preferred Term
20 mg
(N=XX)
30 mg
(N=XX)
40 mg
(N=XX)
Overall 
(N=XX)
      Maximum Severity
n (%)
n (%)
n (%)
n (%)
95% CI
Subjects with at least 1 TEAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Any Event (Total)
      Mild
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
      Moderate
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Severe
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Life-threatening consequences
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
      Death related to AE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
System Organ Class 1
Any Event (Total)
Mild
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Moderate
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
      Severe
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Life-threatening consequences
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Death related to AE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 1
Mild
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
…
Abbreviations: CI = confidence interval; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment emergent adverse event.
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Treatment groups are based on treatment received. The dose received at the 
beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during the Treatment Phase, is presented. AEs were coded using MedDRA 
version 20.1. A TEAE is any AE with an onset date/time between the initiation of study drug and 5 days after the last dose of study drug. This will include any AE with onset prior to 
initiation of study drug and increased severity after the treatment administration. Subjects are counted once for each SOC and once for each PT. The severity shown is the greatest 
severity reported for a particular subject (Death related to AE > Life-threatening consequences > Severe > Moderate > Mild). AEs with a missing severity were counted as Missing.
AEs are displayed by descending frequency of SOC, then PT within SOC, and then alphabetically by PT. 95% Wilson CIs are presented.
SOURCE: Listing 16.2.7.1
Programming note: SOC & PT text should be in proper case in table, as shown in the shell. Ensure correct MedDRA version is printed in footnote. Since treatment groups presented 
are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due 
to tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add “16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 68 of 123
Table 14.3.1.3.2
Incidence of Treatment Emergent Adverse Events by Maximum Severity, SOC, PT, and Treatment
Dose-Optimization Safety Population
(Same shell as Table 14.3.1.3.1)
Programming note: Update footnote with Dose-Optimization Phase Safety Population. Since treatment groups presented are based on the optimized dose (mg) from the Dose-
Optimization Phase, actual doses need to be determined from the data. Update footnote to read “Treatment groups are based on treatment received. The optimized dose is 
presented.”
Table 14.3.1.3.3
Incidence of Treatment Emergent Adverse Events by Maximum Severity, SOC, PT, and Gender
Treatment-Phase Safety Population
(Same shell as Table 14.3.1.3.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. Add 
16.2.4.1 to SOURCE.
Table 14.3.1.3.4
Incidence of Treatment Emergent Adverse Events by Maximum Severity, SOC, PT, and Age 
Treatment-Phase Safety Population
(Same shell as Table 14.3.1.3.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. Add 
16.2.4.1 to SOURCE.
Table 14.3.1.3.5
Incidence of Treatment Emergent Adverse Events by Maximum Severity, SOC, PT, and Duration of Treatment 
Treatment-Phase Safety Population
(Same shell as Table 14.3.1.3.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. Add 
16.2.5.2 to SOURCE.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 69 of 123
Table 14.3.1.3.6
Incidence of Treatment Emergent Adverse Events by Maximum Severity, SOC, PT, and Race 
Treatment-Phase Safety Population
(Same shell as Table 14.3.1.3.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. Add 
16.2.4.1 to SOURCE.
Table 14.3.1.3.7
Incidence of Treatment Emergent Adverse Events by Maximum Severity, SOC, PT, and Site 
Treatment-Phase Safety Population
(Same shell as Table 14.3.1.3.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. Add 
16.2.1 to SOURCE.
Table 14.3.1.3.8
Incidence of Treatment Emergent Adverse Events by Maximum Severity, SOC, PT, and Previous Stimulant Exposure 
Treatment-Phase Safety Population
(Same shell as Table 14.3.1.3.1)
Programming note: Each subgroup will have its own set of columns. If there are too many subgroups such that the table would be too wide, repeat the table for each subgroup. Add 
16.2.8.6 to SOURCE.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 70 of 123
Table 14.3.1.4.1
Incidence of Treatment Related Adverse Events by SOC, PT, and Treatment
Treatment-Phase Safety Population
KP415
20 mg
30 mg
40 mg
Overall
(N=XX)
System Organ Class
(N=XX)
(N=XX)
(N=XX)
Preferred Term
n (%)
n (%)
n (%)
n (%)
95% CI
Subjects with at least 1 Treatment Related 
TEAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
System Organ Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
System Organ Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abbreviations: CI = confidence interval; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment emergent adverse event.
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Treatment groups are based on treatment received. The dose received at the 
beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during the Treatment Phase, is presented. AEs were coded using MedDRA 
version 20.1. A TEAE is any AE with an onset date/time between the initiation of study drug and 5 days after the last dose of study drug. This will include any AE with onset prior to 
initiation of study drug and increased severity after the treatment administration. A treatment related TEAE is an AE that is marked as being possibly, probably, or definitely related 
to treatment. Subjects are counted once for each SOC and once for each PT. AEs are displayed by descending frequency of SOC, then PT within SOC, and then alphabetically by 
PT. 95% Wilson CIs are presented.
SOURCE: Listing 16.2.7.1
Programming note: SOC & PT text should be in proper case in table, as shown in the shell. Ensure correct MedDRA version is printed in footnote. Since treatment groups presented 
are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due 
to tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add “16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 71 of 123
Table 14.3.1.4.2
Incidence of Treatment Related Adverse Events by SOC, PT, and Treatment
Dose-Optimization Safety Population
(Same Shell as Table 14.3.1.4.1)
Programming note: Update footnote with Dose-Optimization Safety Population. Since treatment groups presented are based on the optimized dose (mg) from the Dose Optimization 
Phase, actual doses need to be determined from the data. Update footnote to read “Treatment groups are based on treatment received. The optimized dose is presented.”


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 72 of 123
Table 14.3.1.5.1
Incidence of Treatment Emergent Adverse Events Leading to Study Drug Discontinuation by SOC, PT, and Treatment
Treatment-Phase Safety Population
(Same shell as Table 14.3.1.2.1)
Table 14.3.1.5.2
Incidence of Treatment Emergent Adverse Events Leading to Study Drug Discontinuation by SOC, PT, and Treatment
Dose-Optimization Safety Population
(Same shell as Table 14.3.1.2.1)
Programming note: Update footnote with Dose-Optimization Safety Population. Since treatment groups presented are based on the optimized dose (mg) from the Dose Optimization 
Phase, actual doses need to be determined from the data. Update footnote to read “Treatment groups are based on treatment received. The optimized dose is presented.”
Table 14.3.2.1
Incidence of Serious Adverse Events by SOC, PT, and Treatment
Treatment-Phase Safety Population
(Same shell as Table 14.3.1.2.1)
Table 14.3.2.2
Incidence of Serious Adverse Events by SOC, PT, and Treatment
Dose-Optimization Safety Population
(Same shell as Table 14.3.1.2.1)
Programming note: Update footnote with Dose-Optimization Safety Population. Since treatment groups presented are based on the optimized dose (mg) from the Dose Optimization 
Phase, actual doses need to be determined from the data. Update footnote to read “Treatment groups are based on treatment received. The optimized dose is presented.”


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 73 of 123
Table 14.3.3.1.1
Listing of Adverse Events Leading to Study Drug Discontinuation
Treatment-Phase Safety Population
Subject 
ID
Treatment [1]
System Organ Class/
Preferred Term/
Verbatim Term
Start Date/Time (Study Day)/
End Date/Time (Study Day)
Severity/
Relationship
Outcome/
Study Drug Action Taken/
Other Action Taken
Serious?/
Criteria Met
TEAE? 
[2]
XXXXX
XXXXXXXX
Xxxxxxxxxxxxx/
Xxxxxxxxxxxx/
      Xxxxxxxxx
DDMMMYYYY/hh:mm (X)/
DDMMMYYYY/hh:mm (X)
XXXXXXXXX/
XXXXXXXXXX
XXXXXXXXX/
XXXXXXXXXXXX/
XXXXXXXXXX
XX
XX
XXXXX
XXXXXXXX
Xxxxxxxxxxxxx/
Xxxxxxxxxxxx/
      Xxxxxxxxx
DDMMMYYYY/hh:mm (X)/
DDMMMYYYY/hh:mm (X)
XXXXXXXXX/
XXXXXXXXXX
XXXXXXXXX/
XXXXXXXXXXXX/
XXXXXXXXXX
XX
XX
Abbreviations: TEAE = Treatment emergent adverse event.
Note: Study day is calculated relative to the date of first dose of study drug. AEs were coded using MedDRA version 20.1.
[1] Treatment groups are based on treatment received. The dose received at the beginning of the treatment-phase, or the last dose received if the subject discontinued from the study 
during the treatment-phase, is presented. * = subject was down-titrated due to tolerability issues.
[2] A TEAE is any AE with an onset date/time between the initiation of study drug and 5 days after the last dose of study drug. This will include any AE with onset prior to initiation of 
study drug and increased severity after the treatment administration.
SOURCE: Listing 16.2.7.1
Programming note: If time missing, display “- -:- -”. “Other Action Taken” will be either None, Concomitant Medication, Non-drug Therapy, or Other; if specify text is needed, 
concatenate “Concomitant Medication:” or “Other:” with the text. If Serious? is Yes, concatenate all serious criteria marked as Yes with a semicolon. If no events meet the criteria for 
display, present “No events are reported.” SOC & PT text should be in proper case in table, as shown in the shell. TEAE will be Yes or No. Since treatment groups presented are 
based on the dose (mg) received at the beginning of the treatment-phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to 
tolerability, place an asterisk next to treatment in the treatment column. Add “16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 74 of 123
Table 14.3.3.1.2
Listing of Adverse Events Leading to Study Drug Discontinuation
Dose-Optimization Safety Population
(Same shell as Table 14.3.3.1.1)
Programming Note: Update footnote [1] to read “Treatment groups are based on treatment received. The optimized dose is presented.”


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 75 of 123
Table 14.3.3.2.1
Listing of Serious Adverse Events
Treatment-Phase Safety Population
(Same shell as Table 14.3.3.1.1)
Table 14.3.3.2.2
Listing of Serious Adverse Events
Dose-Optimization Safety Population
(Same shell as Table 14.3.3.1.1)
Programming Note: Update footnote [1] to read “Treatment groups are based on treatment received. The optimized dose is presented.”


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 76 of 123
Table 14.3.3.3.1
Listing of Deaths
Treatment-Phase Safety Population
(Same shell as Table 14.3.3.1.1)
Table 14.3.3.3.2
Listing of Deaths
Dose-Optimization Safety Population
(Same shell as Table 14.3.3.1.1)
Programming Note: Update footnote [1] to read “Treatment groups are based on treatment received. The optimized dose is presented.”


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 77 of 123
Table 14.3.3.4.1
Incidence of Abuse Related Adverse Events by SOC, PT, and Treatment
Treatment-Phase Safety Population
KP415
20 mg
30 mg
40 mg
Overall
(N=XX)
System Organ Class
(N=XX)
(N=XX)
(N=XX)
Preferred Term
n (%)
n (%)
n (%)
n (%)
95% CI
Subjects with at least 1 Abuse 
Related TEAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
System Organ Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
System Organ Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abbreviations: CI = confidence interval; PT = Preferred Term; SOC = System Organ Class. 
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Treatment groups are based on treatment received. The dose received at the 
beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during the Treatment Phase, is presented. AEs were coded using MedDRA 
version 20.1. AEs that are abuse potential-related include the following MedDRA PTs: euphoria-related terms, terms of altered attention, cognition and mood, and 
dissociative/psychotic terms. A treatment related TEAE is an AE that is marked as being possibly, probably, or definitely related to treatment. Subjects are counted once for each 
SOC and once for each PT. AEs are displayed by descending frequency of SOC, then PT within SOC, and then alphabetically by PT. 95% Wilson CIs are presented.
SOURCE: Listing 16.2.7.1
Programming note: SOC & PT text should be in proper case in table, as shown in the shell. Ensure correct MedDRA version is printed in footnote. Since treatment groups presented 
are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due 
to tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add “16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 78 of 123
Table 14.3.3.4.2
Incidence of Abuse Related Adverse Events by SOC, PT, and Age
Treatment-Phase Safety Population
(Same shell as Table 14.3.3.4.1)
Programming note: Column headers will be “Overall”, and each appropriate Age range. Check cut points per Section 9.1.3 of SAP. Remove footnote explaining treatment groups.
Table 14.3.3.4.3
Incidence of Abuse Related Adverse Events by SOC, PT, and Gender
Treatment-Phase Safety Population
(Same shell as Table 14.3.3.4.1)
Programming note: Column headers will be “Overall”, “Male”, and “Female.” Remove footnote explaining treatment groups.
Table 14.3.3.4.4
Incidence of Abuse Related Adverse Events by SOC, PT, and Treatment
Dose-Optimization Safety Population
(Same shell as Table 14.3.3.4.1)
Programming Note: Update footnote to read “Treatment groups are based on treatment received. The optimized dose is presented.”


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 79 of 123
Table 14.3.5.1.1
Summary of Hematology Laboratory Results by Study Visit and Treatment
Treatment-Phase Safety Population
Parameter: XXXXXXXXX
KP415
20 mg
30 mg
40 mg
Overall
Study Visit
(N=XX)
(N=XX)
(N=XX)
(N=XX)
Statistic
Observed
CFB
Observed
CFB
Observed
CFB
Observed
CFB
Baseline [1]
n
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
CV%
XX.XX
XX.XX
XX.XX
XX.XX
Median
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
Visit 11
n
XX
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
CV%
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Visit 17
n
XX
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
CV%
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Continue for other parameters. Sort alphabetically by parameter.
Abbreviations: CFB = change from baseline. CV% = coefficient of variation; NA = not applicable; SD = standard deviation. 
Note: Treatment groups are based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from 
the study during the Treatment Phase, is presented.
[1] Baseline is the Screening Visit 01A for new subjects and either the Screening Visit 01B or the last KP415.E01 Study Visit for roll-over subjects.
SOURCE: Listing 16.2.8.1.1
Programming note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add 
“16.2.5.2” to the SOURCE line.
 
 


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 80 of 123
Table 14.3.5.1.2
Shift from Baseline in Hematology Laboratory Results by Study Visit and Treatment
Treatment-Phase Safety Population
Parameter: XXXXXXX
Baseline [1]
KP415 Overall (N=XX)
Study Visit
Low
Normal
High
Missing
Category
n (%)
n (%)
n (%)
n (%)
Visit 11
Low
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
High
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Visit 17
Low
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
High
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Continue for other parameters and treatment groups. Sort alphabetically by parameter.
Abbreviations: CFB = change from baseline; NA = not applicable. 
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Subjects are summarized overall and 
by treatment received. Treatment groups are based on treatment received. The dose received at the beginning of the Treatment 
Phase, or the last dose received if the subject discontinued from the study during the Treatment Phase, is presented. 
[1] Baseline is the Screening Visit 01A for new subjects and either the Screening Visit 01B or the last KP415.E01 Study Visit for roll-
over subjects.
SOURCE: Listing 16.2.8.1.1
Programming note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment-Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add 
“16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 81 of 123
Table 14.3.5.2.1
Summary of Serum Chemistry Laboratory Results by Study Visit and Treatment 
Treatment-Phase Safety Population
(Same shell as Table 14.3.5.1.1; SOURCE: Listing 16.2.8.1.2)
Table 14.3.5.2.2
Shift from Baseline in Serum Chemistry Laboratory Results by Study Visit and Treatment
Treatment-Phase Safety Population
(Same shell as Table 14.3.5.1.2; SOURCE: Listing 16.2.8.1.2)
Table 14.3.5.3.1
Summary of Quantitative Urinalysis Laboratory Results by Study Visit and Treatment
Treatment-Phase Safety Population
(Same shell as Table 14.3.5.1.1; SOURCE: Listing 16.2.8.1.3)
Table 14.3.5.3.2
Shift from Baseline in Quantitative Urinalysis Laboratory Results by Study Visit and Treatment 
Treatment-Phase Safety Population
(Same shell as Table 14.3.5.1.2; SOURCE: Listing 16.2.8.1.3)


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 82 of 123
Table 14.3.5.3.3
Summary of Qualitative Urinalysis Laboratory Results by Study Visit and Treatment
Treatment-Phase Safety Population
Parameter: XXXXXXXX
KP415
20 mg
30 mg
40 mg
Overall
(N=XX)
Study Visit
(N=XX)
(N=XX)
(N=XX)
Category
n (%)
n (%)
n (%)
n (%)
95% CI
Baseline [1]
Category 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Category 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Category 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Visit 11
Category 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Category 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Category 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Visit 17
Category 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Category 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Category 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Continue for other parameters. Sort alphabetically by parameter.
Abbreviation: CI = confidence interval; NA = not applicable. 
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Subjects are summarized overall and by treatment received. Treatment groups are 
based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during the Treatment
Phase, is presented. 95% Wilson CIs are presented. 
[1] Baseline is the Screening Visit 01A for new subjects and either the Screening Visit 01B or the last KP415.E01 Study Visit for roll-over subjects.
SOURCE: Listing 16.2.8.1.3
Programming note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment-Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add 
“16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 83 of 123
Table 14.3.6.1
Summary of Vital Signs by Study Visit and Treatment 
Treatment-Phase Safety Population
(Same shell as Table 14.3.5.1.1; visits include Baseline, Visit 3 and Visit 4 for new subjects in the Dose Optimization Phase, Visit 5-Visit 17 for subjects in the Treatment-
Phase; parameters include Temperature (C), pulse Rate (bpm), Respiratory Rate (breaths per min) Sitting Systolic Blood Pressure (mmHg), Sitting Diastolic Blood 
Pressure (mmHg), Height (cm), and Weight (kg), BMI (kg/m2), BSA(m2); ensure footnote updated to SOURCE: Listing 16.2.8.2)
Table 14.3.6.2.1
Summary of 12-Lead Electrocardiogram by Study Visit and Treatment 
Treatment-Phase Safety Population
(Same shell as Table 14.3.5.1.1; visits include Baseline, Visit 3 and Visit 4 for new subjects in the Dose Optimization Phase, Visit 5-Visit 17 for subjects in the Treatment-
Phase; parameters include HR, RR, QT, QTcF; ensure footnote updated to SOURCE: Listing 16.2.8.3)


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 84 of 123
Table 14.3.6.2.2
Summary of 12-Lead Electrocardiogram Interpretation by Study Visit and Treatment 
Treatment-Phase Safety Population
KP415
20 mg
30 mg
40 mg
Overall
(N=XX)
Study Visit
(N=XX)
(N=XX)
(N=XX)
Category
n (%)
n (%)
n (%)
n (%)
95% CI
Baseline [1]
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abnormal, Not Clinically Significant
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abnormal, Clinically Significant
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Visit 11
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abnormal, Not Clinically Significant
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abnormal, Clinically Significant
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Visit 17
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abnormal, Not Clinically Significant
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abnormal, Clinically Significant
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abbreviation: CI = confidence interval; NA = not applicable. 
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Treatment groups are based on treatment received. The dose received at the 
beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during the Treatment Phase, is presented. 95% Wilson CIs are presented. 
[1] Baseline is the Screening Visit 01A for new subjects and either the Screening Visit 01B or the last KP415.E01 Study Visit for roll-over subjects.
SOURCE: Listing 16.2.8.3
Programming note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment-Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add 
“16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 85 of 123
Table 14.3.6.3
Summary of Columbia-Suicide Severity Rating Scale (C-SSRS) 
Treatment-Phase Safety Population
KP415
20 mg
30 mg
C-SSRS Section
Pre-treatment
Post-treatment
Pre-treatment
Post-treatment
C-SSRS Item
(N=xx)
(N=xx)
(N=xx)
(N=xx)
Suicidal Ideation
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Wish to be Dead
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Non-Specific Active Suicidal Thoughts
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Active Suicidal Ideation with Any Methods
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Active Suicidal Ideation with Some Intent
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Active Suicidal Ideation with Specific Plan
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Suicidal Behavior
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Actual Attempt
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Subject Engaged in Non-Suicidal Self-
Injurious Behavior 
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Interrupted Attempt
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Aborted Attempt
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preparatory Acts or Behavior
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Suicidal Behavior
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Suicide
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Treatment groups are based on treatment 
received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. The C-SSRS scale consists of a Screening evaluation that assesses the lifetime and more 
recent experience (past 6 months) of the subject with suicidal ideation and behavior, a baseline evaluation that focuses on suicidality since 
Screening that occurs before first dose of study drug (all of which is summarized under “pre-treatment”), and a post-baseline evaluation
(“post-treatment”) that focuses on suicidality since the last study visit. Subjects are counted once for each C-SSRS section and once for 
each C-SSRS item answered “Yes” in pre-treatment and post-treatment.
SOURCE: Listing 16.2.8.4
Programming note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add 
“16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 86 of 123
Table 14.3.6.3 (cont.)
Summary of Columbia-Suicide Severity Rating Scale (C-SSRS) 
Treatment-Phase Safety Population
KP415
40 mg
Overall
C-SSRS Section
Pre-treatment
Post-treatment
Pre-treatment
Post-treatment
C-SSRS Item
(N=xx)
(N=xx)
(N=xx)
(N=xx)
Suicidal Ideation
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Wish to be Dead
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Non-Specific Active Suicidal Thoughts
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Active Suicidal Ideation with Any Methods
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Active Suicidal Ideation with Some Intent
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Active Suicidal Ideation with Specific Plan
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Suicidal Behavior
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Actual Attempt
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Subject Engaged in Non-Suicidal Self-
Injurious Behavior 
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Interrupted Attempt
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Aborted Attempt
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preparatory Acts or Behavior
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Suicidal Behavior
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Suicide
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Treatment groups are based on treatment 
received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. The C-SSRS scale consists of a Screening evaluation that assesses the lifetime and more 
recent experience (past 6 months) of the subject with suicidal ideation and behavior, a baseline evaluation that focuses on suicidality since 
Screening that occurs before first dose of study drug (all of which is summarized under “pre-treatment”), and a post-baseline evaluation
(“post-treatment”) that focuses on suicidality since the last study visit. Subjects are counted once for each C-SSRS section and once for 
each C-SSRS item answered “Yes” in pre-treatment and post-treatment.
SOURCE: Listing 16.2.8.4
Programming note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add 
“16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 87 of 123
Table 14.3.6.4
Summary of Concomitant Medications by ATC Class Level 4, PT, and Treatment
Treatment-Phase Safety Population
KP415
20 mg
30 mg
40 mg
Overall
(N=XX)
ATC Class Level 4
(N=XX)
(N=XX)
(N=XX)
Preferred Term (ATC Class Level 5)
n (%)
n (%)
n (%)
n (%)
95% CI
Subjects with at least 1 Concomitant 
Medication
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
ATC Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
ATC Class 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
(XX.X%, XX.X%)
Abbreviations: ATC = Anatomical Therapeutic Chemical; CI = confidence interval; PT = Preferred Term. 
Note: Percentages are n/Number of subjects in the Treatment-Phase Safety Population*100. Treatment groups are based on treatment received. The dose received at 
the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during the Treatment Phase, is presented. 95% Wilson CIs 
are presented.  Medications were coded using WHO-DDE version September 2017. Concomitant medications are all medications that were continuing or starting after 
first dose of study drug. Medications are displayed by descending frequency of Anatomic Therapeutic Chemical (ATC) Level 4 classification, by PT within ATC, and 
then alphabetically. Subjects were counted only once for each ATC and PT. 95% Wilson CIs are presented.
SOURCE: Listing 16.2.8.6
Programming note: ATC & PT text should be in proper case in table, as shown in the shell. Ensure correct WHO-DDE is printed in footnote. Since treatment groups presented are 
based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to 
tolerability, this should be mentioned in the footnote as “Subject XXXXXX was down titrated due to tolerability issues.”; add “16.2.5.2” to the SOURCE line.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 88 of 123
13.9.
Planned Listing Shells


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 89 of 123
Listing 16.2.1
Subject Disposition
All Subjects
Subject ID
Treatment [1]
Site
Did Subject 
Complete 
Study?
Date of 
Completion/Discontinuation 
(Study Day)
Date of Last Visit 
(Study Day)
Reason for Discontinuation
Last Dose Received Prior 
to Discontinuation
XXXXXX
XXXXXX
XXXXXX
Yes
DDMMMYYYY (XX)
DDMMMYYYY (XX)
XXXXXX
XXXXXX
XXXXXX
Yes
DDMMMYYYY (XX)
DDMMMYYYY (XX)
XXXXXX
XXXXXX
XXXXXX
Yes
DDMMMYYYY (XX)
DDMMMYYYY (XX)
XXXXXX
XXXXXX
XXXXXX
No
DDMMMYYYY (X)
DDMMMYYYY (X)
XXXXXXXXXX: XXXXXXXXX
XXX
XXXXXX
XXXXXX
XXXXXX
No
DDMMMYYYY (XX)
DDMMMYYYY (XX)
XXXXXXXXXXXXXXXXXXXXXX
XXX
Abbreviation: NA = not applicable.     
Note: Study day is calculated relative to the date of first dose of study drug.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. * subject was down-titrated due to tolerability issues.
Programming Note: If reason for early termination is Other, concatenate the specify text as follows: “Other: XXXXXXXXX”. If reason for early termination is lost to follow-up, 
concatenate with date of last contact as follows: “Lost to follow-up; date of last contact: DDMMMYYYY”. Since treatment groups presented are based on the dose (mg) received at the 
beginning of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the 
treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 90 of 123
Listing 16.2.2.1
Inclusion and Exclusion Criteria Not Met
All Subjects
Date (Study Day) of:
All Inclusion
Criteria Met?
Any Exclusion
Criteria Met?
Subject ID
Treatment [1]
Screening/Informed Consent
Informed Assent
[2]
[3]
XXXXXX
XXXXXX
DDMMMYYYY (-X)
DDMMMYYYY (-X)
Yes
No
XXXXXX
XXXXXX
DDMMMYYYY (-X)
DDMMMYYYY (-X)
No: 02, 07
No
XXXXXX
XXXXXX
DDMMMYYYY (-X)
DDMMMYYYY (-X)
No: 02
No
XXXXXX
XXXXXX
DDMMMYYYY (-X)
DDMMMYYYY (-X)
Yes
Yes: 05
XXXXXX
XXXXXX
DDMMMYYYY (-X)
DDMMMYYYY (-X)
Yes
No
XXXXXX
XXXXXX
DDMMMYYYY (-X)
DDMMMYYYY (-X)
Yes
No
Note: Study day is calculated relative to the date of first dose of study drug.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the 
subject discontinued from the study during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
[2] 02 Subject must have a body weight of at least 21 kg at Screening; 07 = Subject must meet Diagnostic and Statistical Manual of Mental 
Disorders - Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD (combined, inattentive, or hyperactive/impulsive presentation) per 
clinical evaluation and confirmed by the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). If the MINI-KID 
assessment is available from a previous study with KP415, it does not need to be repeated.
[3] 05 = Subject has a positive urine MPH screen at Visit 5.
Programming note: If more than 1 inclusion or exclusion criterion number exists, concatenate with a comma as shown above. Decode any relevant criteria in the footnotes as shown 
in the example. If no criteria are present for a column, remove the [2] and/or [3] from the column header. Since treatment groups presented are based on the dose (mg) received at the 
beginning of the Treatment-Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the 
treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 91 of 123
Listing 16.2.2.2
Protocol Deviations
All Subjects
Subject ID
Treatment [1]
Event Type
Violation
Level
Description
XXXXXX
XXXXXXX
XXXXXXXXXXX
MAJOR
XXXXXXX
XXXXXXXXXXXXXX
MINOR
XXXXXXXXXXXXXXX
XXXXXX
XXXXXXX
XXXXXXXXXXXX
MINOR
XXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXX
MINOR
XXXXXXXXXXX
XXXXXX
XXXXXXXXX
XXXXXXXXXXXX
MAJOR
XXXXXXXXXXXXXXXXXXXX
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the 
subject discontinued from the study during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
Programming note: The structure of this listing may change depending on the information in the protocol deviations file. Since treatment groups presented are based on the dose 
(mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an 
asterisk next to treatment in the treatment column. 


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 92 of 123
Listing 16.2.3
Analysis Populations
All Subjects
Subject ID
Treatment [1]
Treatment-
Phase 
Safety
[2]
Efficacy
[3]
Dose-
Optimization 
Safety
[4]
Reason(s) for Exclusion
XXXXXX
XXXXXX
Yes
Yes
No
Dose-Optimization Safety Population: 
Subject did not have at least 1 post-dose 
safety assessment in the Dose 
Optimization Phase.
XXXXXX
XXXXXXX
Yes
Yes
Yes
XXXXXX
XXXXXX
No
No
No
Treatment-Phase Safety: Subject did not 
receive at least 1 dose of study drug.
[1] Treatment is based on treatment received. The dose received at the beginning of the treatment-phase, or the last 
dose received if the subject discontinued from the study during the treatment-phase, is presented.
[2] The Treatment-Phase Safety Population includes all subjects who are enrolled in the Treatment Phase and
received at least 1 dose of study medication in the Treatment Phase and had at least 1 post-dose safety assessment 
in the Treatment Phase. * = subject was down-titrated due to tolerability issues.
[3] The Efficacy Population includes all enrolled subjects who received at least 30 days of study medication in the 
Treatment Phase and had adequate data to assess the change from baseline of the efficacy parameters and who 
had no protocol deviations that could affect the efficacy parameters.
[4] The Dose-Optimization Safety Population includes all subjects who are enrolled in the Dose Optimization Phase 
and received at least 1 dose of study medication in the Dose Optimization Phase and had at least 1 post-dose safety 
assessment in the Dose Optimization Phase.
Programming note: Concatenate all reasons for exclusion with a semi-colon. Since treatment groups presented are based on the dose (mg) received at the beginning of the 
Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the 
treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 93 of 123
Listing 16.2.4.1
Demographics and Baseline Characteristics
All Subjects
Child-Bearing
Date of
Age
Weight
Height
BMI
BSA
Subject ID
Treatment [1]
Sex
Potential?
Birth
(years)
Ethnicity
Race
(kg)
(cm)
(kg/m2)
(m2) [2]
XXXXXX
XXXX
XXXX
DDMMMYYY
XX
XXXXXXX
XXXXXXX
XX.X
XX.X
XX.XX
XX.XX
XXXXXX
XXXXXX
XXXXXX
No
DDMMMYYY
XX
XXXXXXX
XXXXXX
XX.X
XX.X
XX.XX
XX.XX
XXXXXX
XXXXXX
XXXXXX
Yes
DDMMMYYY
XX
XXXXXXX
XXXXXX
XX.X
XX.X
XX.XX
XX.XX
XXXXXX
XXXX
XXXX
DDMMMYYY
XX
XXXXXXX
XXXXX
XX.X
XX.X
XX.XX
XX.XX
XXXXXX
XXXXXX
XXXXXX
No
DDMMMYYY
XX
XXXXXXX
XXXXXX
XX.X
XX.X
XX.XX
XX.XX
XXXXXX
XXX
XXXX
DDMMMYYY
XX
XXXXXX
XXXXXX
XX.X
XX.X
XX.XX
XX.XX
Abbreviation: BMI = Body Mass Index; BSA = body surface area.
Note: Height, weight, BMI, and BSA are the values at Screening.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
[2] BSA = [height(cm)
weight(kg)]/3600
Programming Note: If race is other, concatenate “Other:” with specify text. If subject has multiple races, concatenate them. Since treatment groups presented are based on the dose 
(mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an 
asterisk next to the treatment in the treatment column. 


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 94 of 123
Listing 16.2.4.2
Medical History
All Subjects
System Organ Class/
Preferred Term/
Start Date (Study Day)/
Subject ID
Treatment [1]
Verbatim Term
End Date (Study Day)/
XXXXXX
XXXXXXXXX
XXXXXXXXXXXXXXXXX/
DDMMMYYYY (X)/
XXXXXXXXXXXXXX/
DDMMMYYYY (X)
XXXXXXXXXXXXX
XXXXXXXXX/
MMMYYYY (X)/
XXXXXXXXXXXXXXX/
Ongoing
XXXXXXXXXXX
XXXXXXXXX/
MMMYYYY (X)/
XXXXXXXXXXXXXXX/
Ongoing
XXXXXXXXXXX
XXXXXX
XXXXXXXXXX
XXXXXXXXX/
DDMMMYYYY (X)/
XXXXXXXXXXXXXX/
DDMMMYYYY (X)
XXXXXXXXXXXXXXXXXXXXXX
Note: Study day is calculated relative to the date of first dose of study drug. Medical history was coded using MedDRA version 20.1. 
Only subjects with medical history recorded are listed.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if 
the subject discontinued from the study during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability 
issues.
Programming note: SOC & PT text should be in proper case in table, as shown in the shell. Since treatment groups presented are based on the dose (mg) received at the beginning 
of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in 
the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 95 of 123
Listing 16.2.4.3
ADHD Diagnosis and Confirmation
All Subjects
Date of ADHD Diagnosis
Subject ID
Treatment [1]
Has an ADHD Diagnosis been confirmed?
(Study Day)
XXXXXX
XXXXXXXXX
XXX
DDMMMYYYY (X)
XXXXXX
XXXXXXXXX
XXX
DDMMMYYYY (X)
Abbreviations: ADHD = attention-deficit hyperactivity disorder
Note: Study day is calculated relative to the date of first dose of study drug. 
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if 
the subject discontinued from the study during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability 
issues.
Programming note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 96 of 123
Listing 16.2.4.4
Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)
All Subjects
Was
Interview
Subject ID
Treatment 
[1]
Assessment 
Performed?
Date (Study 
Day)
Start/Stop 
Time
Total Time
Module
Item
Response
Primary Diagnosis?
XXXXXX
XXXXXX
XXXX
DDMMMYYYY
(-X)
hh:mm/
hh:mm
XXXX
Major Depressive 
Episode
Current (Past 2 weeks)
XX
Past
XX
Recurrent
XX
Major Depressive 
Disorder
Current (Past 2 weeks)
XX
XXX
Past
XX
XXX
Recurrent
XX
XXX
Suicidality
Current (Past Month)
XX
XXX
Lifetime
XX
XXX
Lifetime Attempt Level
XXXXXX
X
Suicide Behavior 
Disorder
Current (In Past Year)
XX
XXX
In early remission (1-2 years 
ago)
XX
XXX
…
Abbreviations: MINI-KID= Mini International Neuropsychiatric Interview for Children and Adolescents
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during the Treatment
Phase, is presented. * = subject was down-titrated due to tolerability issues.
Programming note: Continue for other categories and assessments. Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment
Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the treatment 
column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 97 of 123
Listing 16.2.5.1
Capsule Swallowing Test
All Subjects
Subject ID
Treatment [1]
Was Subject Able to Swallow the Capsule?
XXXXXX
XXXXXXXX
XXX
XXXXXX
XXXXXXXX
XXX
XXXXXX
XXXXXXXX
XXX
XXXXXX
XXXXXXXX
XXX
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
Programming note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 98 of 123
Listing 16.2.5.2
Study Drug Dispensation and Return 
All Subjects
Subject ID
Treatment [1]
Study Visit
Study 
Medication 
Assessment 
Type
Study 
Medication 
Dispensed/
Returned?
Date Dispensed/
Returned 
(Study Day)
Number of 
Capsules 
Dispensed/
Returned
Dose 
Adjusted?
Adjusted 
Dose 
Level (mg)
Number of Doses 
Missed (Reason)
Subject 
Compliant?
(% Compliance) 
[2]
XXXXXX
XXXXXXXX
Visit 2 
Dispensed
Yes
DDMMMYYYY (X)
XX
No
XX
Returned
Yes
DDMMMYYYY (X)
XX
XX
Yes (100%)
Visit 3
Dispensed
Yes
DDMMMYYYY (XX)
XX
No
XX
Returned
Yes
DDMMMYYYY (XX)
XX
XX (XXXX)
Yes (80%)
Visit 4
Dispensed
Yes
DDMMMYYYY (XX)
XX
Yes: XXXX
XX
Returned
Yes
DDMMMYYYY (XX)
XX
XX (XXXX)
No (60%): 
XXXXXXX
Visit 5
Dispensed
Yes
DDMMMYYYY (XX)
XX
No
XX
Returned
Yes
DDMMMYYYY (XX)
XX
XX
Yes (100%)
Visit 6
Dispensed
Yes
DDMMMYYYY (X)
XX
No
XX
Returned
Yes
DDMMMYYYY (X)
XX
XX (XXXX)
Yes (85%)
Note: Study day is calculated relative to the date of first dose of study drug.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during the 
Treatment Phase, is presented.
[2] Acceptable compliance is defined as 80-100% of total doses (inclusive).
Programming note: If med not dispensed or returned, or subject is not compliant, concatenate reason like: “No: XXXXXX”. If Dose was adjusted, concatenate reason like: “Yes: 
XXXX”. If Any doses were missed, concatenate reason like: “#: XXXXXX”


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 99 of 123
Listing 16.2.6.1
ADHD-Rating Scale-5
All Subjects
Subject 
ID
Treatment 
[1]
Study 
Visit
Date of Assessment 
(Study Day)
Category
Assessment
Numeric 
Result
Text Result
XXX-XX
XXXXXX
XXXXXX
DDMMMYYYY (XX)
How often does your 
child display this 
behavior?
Fails to give close attention to details or 
makes careless mistakes in schoolwork
or during other activities
XX
XXXXXXXXX
Has difficulty sustaining attention in 
tasks or play activities
XX
XXXXXXXXX
Does not seem to listen when spoken 
to directly
XX
XXXXXXXX
Does not follow through on instructions 
and fails to finish schoolwork or chores
XX
XXXXXXXX
Has difficulty organizing tasks and 
activities
XX
XXXXXXXX
…
…
Subscale and Total 
Scores
Inattention Subscale Score
XX
Hyperactivity/Impulsivity Subscale 
Score
XX
Total ADHD-RS-5 Score
XX
Note: Study day is calculated relative to the date of first dose of study drug.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment-Phase, is presented. * = subject was down-titrated due to tolerability issues.
[2] Change from baseline is calculated as Numeric Result – Baseline.
Programming Note: Continued for other categories and assessments. Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment
Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the treatment
phase.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 100 of 123
Listing 16.2.6.2
Clinical Global Impression (CGI) – Severity
All Subjects
Subject
Date of
Assessment
Reason Not
Numeric
Text
ID
Treatment [1]
Study Visit
(Study Day)
Performed
Result
Result
XXX-XX
XXXXXXX
XXXXXXX
DDMMMYYYY (X)
X
XXXXXXX
XXXXXXX
DDMMMYYYY (X)
X
XXXXXXX
Abbreviation: CGI-S = Clinical Global Impression - Severity.
Note: Study day is calculated relative to the date of first dose of study drug. The CGI-S score is based on the following 
question regarding severity of illness: Considering your total clinical experience with this particular population, how mentally ill 
is the patient at this time?
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose 
received if the subject discontinued from the study during the Treatment Phase, is presented. * = subject was down-titrated 
due to tolerability issues.
Programming note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 101 of 123
Listing 16.2.6.3
Clinical Global Impression (CGI) – Improvement
All Subjects
Same shell as Listing 16.2.6.2; use the following footnotes:
Abbreviation: CGI-I = Clinical Global Impression – Improvement.
Note: Study day is calculated relative to the date of first dose of study drug. The CGI-I score is based on the following question regarding global improvement: Rate total improvement 
whether or not, in your judgment, it is due entirely to drug treatment. Compared to his/her condition at admission to the project, how much has patient changed?


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 102 of 123
Listing 16.2.6.4
Children’s Sleep Habits Questionnaire (CSHQ)
All Subjects
Subject 
ID
Treatment 
[1]
Study 
Visit
Date of Assessment 
(Study Day)
Category
Assessment
Numeric
Result
Text Result
XXX-XX
XXXXXX
XXXXXX
DDMMMYYYY (XX)
Bedtime
Child’s bedtime
hh:mm
1) Child goes to bed at the same time at night
XX
XXXXXX
2) Child falls asleep within 20 minutes after 
going to bed
XX
XXXXXXXX
3) Child falls asleep alone in own bed
XX
XXXXXXXXX
4) Child falls asleep in parent's or sibling's bed
XX
XXXXXX
5) Child needs parent in the room to fall asleep
XX
XXXXXXXX
6) Child struggles at bedtime (cries, refuses to 
stay in bed, etc.)
XX
XXXXXXXXX
7) Child is afraid of sleeping in the dark
XX
XXXXXX
8) Child is afraid of sleeping alone
XX
XXXXXXXX
Sleep Behavior
Child's usual amount of sleep each day (hours)
XX
XXXXXX
Child's usual amount of sleep each day 
(minutes)
XX
XXXXXXXX
9) Child sleeps too little
XX
XXXXXXXXX
…
…
Subscale and Total 
Scores
Subcale 1: Bedtime Resistance
XX
Subscale 2: Sleep Onset Delay
XX
…
Subscale 8: Daytime Sleepiness
XX
Total Sleep Disturbance Score
XX
Note: Study day is calculated relative to the date of first dose of study drug. Assessments that are marked as Not Done are not included in the listing.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
Programming Note: Continued for other categories and assessments. Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment
Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the treatment 
column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 103 of 123
Listing 16.2.7.1
Adverse Events
All Subjects
System Organ Class/
Outcome/
Preferred Term/
Start Date (Study Day)/
Severity/
Study Drug Action Taken/
Serious?/
Abuse 
Subject ID
Treatment 
[1]
TEAE?
Verbatim Term
End Date (Study Day)
Relationship
Other Action Taken
Criteria Met
Related?
[2]
XXX-XX
XXXXXX
XXX
XXXXXXXXXXXXXXXXX/
DDMMMYYYY/
XXXXXXXXX
/
XXXXXXXXXXXX/
XX/
XXX
XXXXXXXXXXXXXX/
DDMMMYYYY
XXXXXXXX
XXXXXXXXXXXXX/
XXXXXXXXX
      XXXXXXXXXXXXX
XXXXXXXXXXXXXXX
XXXXXX
XXX
XXXXXXXXX/
DDMMMYYYY/
XXXXXXXXX
/
XXXXXXXXXXXXX
XX
XXX
XXXXXXXXXXXXXXX/
Ongoing
XXXXXXXX
XXXXXXXXXXX
XXXXXX
XXX
XXXXXXXXX/
DDMMMYYYY/
XXXXXXX/
XXXXXXXXXXXXXX
XX
XXX
XXXXXXXXXXXXXX/
DDMMMYYYY
XXXXXXX
XXXXXXXXXXXXXXXX
Abbreviation: TEAE = Treatment emergent adverse event.
Note: Study day is calculated relative to the date of first dose of study drug. AEs were coded using MedDRA version 19.1. A TEAE is any adverse event with an onset date/time between 
the initiation of study drug and 5 days after the last dose of study drug. This will include any AE with onset prior to initiation of study drug and increased severity after the treatment 
administration.
[1] Treatment is based on treatment received. The dose received at the beginning of the treatment-phase, or the last dose received if the subject discontinued from the study during the 
treatment-phase, is presented. * = subject was down-titrated due to tolerability issues.
[2] Abuse-related AEs include the following MedDRA Preferred Terms: Euphoric mood; Elevated mood; Feeling abnormal; Feeling drunk; Feeling of relaxation; Dizziness; Thinking 
abnormal; Hallucination; Inappropriate affect; Somnolence; Mood disorders and disturbances; psychosis; aggression; confusion and disorientation; drug tolerance; habituation; drug 
withdrawal syndrome; substance-related disorders.
Programming note: “Other Action Taken” will be either None, Medication Required, Relevant Procedure, or Other; if specify text is needed, concatenate “Relevant Procedure:” or 
“Other:” with the text. If Serious? is Yes, concatenate all serious criteria marked as Yes with a semicolon. If no events meet the criteria for display, present “No events are reported.” 
SOC & PT text should be in proper case in table, as shown in the shell. Ensure correct MedDRA version is printed in footnote. Since treatment groups presented are based on the 
dose (mg) received at the beginning of the treatment-phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, 
place an asterisk next to the treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 104 of 123
Listing 16.2.8.1.1
Clinical Laboratory Data: Hematology
All Subjects
Subject 
ID
Treatment [1]
Parameter (unit)
Study Visit
Date of Assessment 
(Study Day)
Standard 
Results
Change 
from 
Baseline [2]
Reference 
Range [3]
Reference 
Range Flag
Accession 
Number
Comments/Reason 
Not Done
XXXXXX
XXXXXXXX
Red Blood Cell Count 
XXXXXX
DDMMMYYYY (X)
XX
XX – YY
XXXXXXX
XXXXXX
DDMMMYYYY (X)
XX
XX
XX – YY
XXXXXXX
XXXXXX
DDMMMYYYY (X)
XX
XX
XX – YY
XXXXXXX
XXXXXX
DDMMMYYYY (X)
XX
XX
XX – YY
XXX
XXXXXXX
XXXXXX
DDMMMYYYY (X)
XX
XX
XX – YY
XXXXXXX
XXXXXX
DDMMMYYYY (X)
XX
XX
XX – YY
XXXXXXX
XXXXXX
DDMMMYYYY (X)
XX
XX
XX – YY
XXXXXXX
XXXXXX
DDMMMYYYY (X)
XX
XX
XX – YY
XXXXXXX
XXXXXX
ND
XXXXXXX
XXXXXX
DDMMMYYYY (X)
XX
XX
XX – YY
XXXXXXX
Abbreviations: A = abnormal; CS = clinically significant; H = high; L = low; ND = not done.
Note: Study day is calculated relative to the date of first dose of study drug. 
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment-Phase, or the last dose received if the subject discontinued from the study during the Treatment
Phase, is presented. * = subject was down-titrated due to tolerability issues.
[2] Baseline is the Screening Visit 01A for new subjects and either the Screening Visit 01B or the last KP415.E01 Study Visit for roll-over subjects
[3] Reference range is used to identify potentially clinically significant laboratory values.
Programming note: update abbreviations to reflect actual data. If test was not done, set results to ND; make sure last column is populated accordingly. Since treatment groups 
presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than 
planned due to tolerability, place an asterisk next to the treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 105 of 123
Listing 16.2.8.1.2
Clinical Laboratory Data: Serum Chemistry
All Subjects
(Same shell as Listing 16.2.8.1)
Listing 16.2.8.1.3
Clinical Laboratory Data: Urinalysis
All Subjects
(Same shell as Listing 16.2.8.1; remove “(unit)” from 2nd column header)
Listing 16.2.8.1.4
Clinical Laboratory Data: Urine Drug Screen and Pregnancy Tests
All Subjects
(Same shell as Listing 16.2.8.1; remove “(unit)” from 2nd column header; do not display Reference Range or Accession number columns)


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 106 of 123
Listing 16.2.8.2
Vital Signs
All Subjects
Subject 
ID
Treatment
[1]
Study 
Visit
Date of
Assessment
(Study Day)
Temp
(C)
Pulse Rate
(beats/min)
Respiratory Rate
(breaths/min)
Sitting Blood
Pressure (mmHg)
Height
(cm)
Weight
(kg)
BSA
(m2)
[2]
BMI
(kg/m2)
Systolic
Diastolic
XXXXXX
XXXXXX
XXXXXX
DDMMMYYYY (X)
XX.X
XX
XX
XXX
XX
XX.X
XXX
XX.X
XX.X
XXXXXX
DDMMMYYYY (X)
XX.X
XX
XX
XXX
XX
XXX
XXXXXX
DDMMMYYYY (X)
XX.X
XX
XX
XXX
XX
XXX
XXXXXX
DDMMMYYYY (X)
ND
ND
ND
ND
ND
ND
XXXXXX
DDMMMYYYY (X)
XX.X
XX
XX
XXX
XX
XXX
Abbreviation: BMI = Body Mass Index; BSA = body surface area; ND = not done.
Note: Study day is calculated relative to the date of first dose of study drug.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
[2] BSA = [height(cm)
weight(kg)]/3600
Programming Note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 107 of 123
Listing 16.2.8.3
12-Lead Electrocardiogram (ECG) Quantitative Results
All Subjects 
Study
Date/Time of ECG
Investigator
Heart Rate
RR Interval
QT Interval
QTcF Interval
Subject ID
Treatment [1]
Visit
(Study Day)
Interpretation
(bpm)
(msec)
(msec)
(msec)
Comments
XXXXXX
XXXXXX
XXXXXX
DDMMMYYYY/
hh:mm (X)
XXXXXXX
XXX
XXX
XXX
XXX
XXXXXX
DDMMMYYYY/
hh:mm (X)
XXXXXXXXXXX
XXX
XXX
XXX
XXX
XXXXXX
DDMMMYYYY/
hh:mm (X)
XXXXXXXXX
XXX
XXX
XXX
XXX
XXXXXX
DDMMMYYYY/
hh:mm (X)
XXXXXXX
XXX
XXX
XXX
XXX
XXXXXX
DDMMMYYYY/
hh:mm (X)
XXXXXXXXXXX
XXX
XXX
XXX
XXX
XXXXXX
DDMMMYYYY/
hh:mm (X)
XXXXXXXXX
XXX
XXX
XXX
XXX
XXXXXX
ND
XXXXXX
XXXXXX
XXXXXX
DDMMMYYYY/
hh:mm (X)
XXXXXXX
XXX
XXX
XXX
XXX
XXXXXX
DDMMMYYYY/
hh:mm (X)
XXXXXXXXXXX
XXXX
XXXX
XXXX
XXXX
XXXXXXXXX
Abbreviation: HR = heart rate; ND = not done. 
Note: Study day is calculated relative to the date of first dose of study drug.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
Programming note: if assessment not done at a visit, put ‘ND’ in the date column. Since treatment groups presented are based on the dose (mg) received at the beginning of the 
Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the 
treatment column. Add columns for any additional parameters provided by the central reader. 


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 108 of 123
Listing 16.2.8.4
Columbia-Suicide Severity Rating Scale (C-SSRS)
All Subjects 
Subject
ID
Treatment [1]
Study Visit
Date/Time
of Assessment
(Study Day)
Reference Period
Category
Assessment
Result
XXX-XX
XXXXXX
XXXXXX
DDMMMYYYY/
Lifetime
Suicidal Ideation
1. Wish to be dead
XX
HH:MM (XX)
If yes, describe:
2. Non-Specific Active Suicidal 
Thoughts
XX
If yes, describe:
3. Active Suicidal Ideation with 
Any Methods (not Plan) without 
Intent to Act
XX
If yes, describe:
4. Active Suicidal Ideation with 
Some Intent to Act, without 
Specific Plan
XX
If yes, describe:
5. Active Suicidal Ideation with 
Specific Plan and Intent
XX
If yes, describe:
Intensity of Ideation
Was the answer to “1. Wish to be 
dead” and/or “2. Non-Specific 
Active Suicidal Thoughts” equal to 
“Yes”?
XX
Most Severe Ideation Type # (1-5)
X
Description of Ideation
XXXXXXXXXXXXXXX
Frequency
1 = Only one time
Note: Study day is calculated relative to the date of first dose of study drug. Assessments that are marked as Not Done are not included in the listing.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
Programming Note: Continued for other categories and assessments. Screening and Baseline time points will have Lifetime and Past 6 months test periods.  Other time points will 
have “Since last visit” test period. Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be 
determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 109 of 123
Listing 16.2.8.5
Physical Examination 
All Subjects
Subject
ID
Treatment [1]
Study
Visit
Exam Date
(Study Day)
Body System
Result
Abnormal Findings
Clinically Significant?
XXXXXX
XXXXXXX
XXXXXXX
DDMMMYYYY
(-X)
General 
Appearance
Normal
Skin
Abnormal
XXXXXXXX
No
Head and Neck
Normal
Lymph Nodes
Normal
Thyroid
Normal
Musculoskeletal
Normal
Extremeties
Normal
Cardiovascular
Normal
Lungs
Normal
Abdomen
Normal
Neurological
Normal
Note: Study day is calculated relative to the date of first dose of study drug.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject 
discontinued from the study during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
Programming note: Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the 
data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 110 of 123
Listing 16.2.8.6
Prior and Concomitant Medications
All Subjects
Subject ID
Treatment [1]
Prior/
Concomitant
[2]
Reason for 
Use
ATC Class (Level 4)/
Preferred Term (ATC Level 5)/
Verbatim Term
Start Date (Study Day)/
End Date (Study Day)
Dose (unit) /
Total Daily Dose
Route/
Frequency
XXXXXX
XXXXXX
Prior
XXXXXXXX
XXXXXXXXXXXXXXXXX/
DDMMMYYYY (X)/
XXX (XXX)/
XXX
XXXXXXXX/
XXXXXXX
XXXXXXXXXXXXXX/
DDMMMYYYY (X)
XXXXXXXXXXXXX
Both
XXXXXXXX
XXXXXXXXX/
DDMMMYYYY (X)/
XXX (XXX) /
XXX
XXXXXXXXXXXXXXX/
Ongoing
XXXXXXXXXXX
Concomitant
XXXXXXX
XXXXXXXXX/
DDMMMYYYY (X)/
XXX (XXX) /
XXX
XXXXXXXXXXXXXX/
DDMMMYYYY (X)
XXXXXXXXXXXXXXXXXXXXXX
Abbreviation: ATC = anatomic therapeutic chemical; NA = Not applicable.
Note: Study day is calculated relative to the date of first dose of study drug. Medications were coded using WHO-DDE version September 2017.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study during 
the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
[2] Prior indicates medication that was started and stopped prior to dosing of study drug. Concomitant indicates medication that started during the treatment period. Both indicates 
medication that was started prior to dosing of study drug and continued during the treatment period.
Programming note: If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). Sort by subject, start date/time, 
end date/time, ATC level 4 & PT. ATC & PT text should be in proper case in table, as shown in the shell. Since treatment groups presented are based on the dose (mg) received at the 
beginning of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the 
treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 111 of 123
Listing 16.2.8.7
Lifetime History of ADHD Treatment
All Subjects
Subject 
ID
Treatment 
[1]
Medication/Therapy
Name
ADHD Drug 
Class
Dose 
(Dose 
Unit)
Route
Frequency
Reason for 
Use
Start Date
(Study Day)
Was this 
Medication 
Started 
Within the 
Last 14 
Days?
Ongoing?
End Date 
(Study Day)
XXXXXX
XXXXXX
XXXXXXXX
XXXXXXXX
XXXXX 
(XXXX)
XXXXXXXX
XXXXXXXX
XXXXXXXX
XXXXXXXX
(XXX)
XXX
XXX
XXXXXXXX
(XXX)
XXXXXXXX
XXXXXXXX
XXXXX 
(XXXX)
XXXXXXXX
XXXXXXXX
XXXXXXXX
XXXXXXXX
(XXX)
XXX
XXX
XXXXXXXX
(XXX)
XXXXXXXX
XXXXXXX
XXXXX 
(XXXX)
XXXXXXX
XXXXXXX
XXXXXXX
XXXXXXXX
(XXX)
XXX
XXX
XXXXXXXX
(XXX)
Abbreviation: ADHD = attention-deficit hyperactivity disorder; NA = Not applicable.
Note: Study day is calculated relative to the date of first dose of study drug. 
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
Programming note: If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). Sort by subject, start date/time, 
end date/time, ADHD Drug Class, Medication/Therapy Name. ADHD Drug Class and Medication/Therapy Name text should be in proper case in table, as shown in the shell. Since 
treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual doses need to be determined from the data. If a subject receives a 
lower dose than planned due to tolerability, place an asterisk next to the treatment in the treatment column.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 112 of 123
Listing 16.2.8.8
ADHD Medication Washout
All Subjects
Subject ID
Treatment [1]
Was the Subject Reminded of the 
Washout?
Were ADHD Medications 
Washed Out?
Start Date of Washout
(Study Day)
End Date of Washout 
(Study Day)
XXXXXX
XXXXXX
XXX
XXX
DDMMMYYYY
(XXX)
DDMMMYYYY
(XXX)
XXXXXX
XXXXXX
No: XXXXXXXX
XXX
DDMMMYYYY
(XXX)
DDMMMYYYY
(XXX)
XXXXXX
XXXXXX
XXX
XXX
DDMMMYYYY
(XXX)
DDMMMYYYY
(XXX)
Abbreviations: ADHD = attention-deficit hyperactivity disorder.
[1] Treatment is based on treatment received. The dose received at the beginning of the Treatment Phase, or the last dose received if the subject discontinued from the study 
during the Treatment Phase, is presented. * = subject was down-titrated due to tolerability issues.
Programming note: Sort by subject, start date, end date. Since treatment groups presented are based on the dose (mg) received at the beginning of the Treatment Phase, actual 
doses need to be determined from the data. If a subject receives a lower dose than planned due to tolerability, place an asterisk next to the treatment in the treatment column. If the 
subject was not reminded of the washout, concatenate reason like: “No: XXXXXX”.


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 113 of 123
13.10.
Planned Figure Shells
Not Applicable


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 114 of 123
Appendix 1: Premier Research Library of Abbreviations
Abbreviation
Definition
aCRF 
annotated case report form
AD
associated documents
ADHD
attention-deficit hyperactivity disorder
ADHD-RS-5
Attention-Deficit Hyperactivity Disorder Rating Scale 5
ADR
adverse drug reactions
AE
adverse event
AESI
adverse events special interest
AIC
Akaike information criterion
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AR(1)
Autoregressive
AST
aspartate aminotransferase
ATC
anatomical therapeutic chemical
BLQ
beneath limit of quantification
BMI
body mass index
BSA
body surface area
CCGs
CRF completion guidelines
CD
compact disc
CDISC
clinical data interchange standards consortium


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 115 of 123
Abbreviation
Definition
CEC
central ethics committee
CFR
code of federal regulations
CGI-I
Clinical Global Impressions–Improvement
CGI-S
Clinical Global Impressions–Severity
CI
confidence intervals
CIOMS
council for international organizations of medical sciences
CIP
clinical investigational plan
CM
clinical manager or centimeter
CMP
clinical monitoring plan
COV
close out visit
CRA
clinical research associate
CRF
case report form
CRO
contract research organization
CS
clinically significant or compound symmetry
CSHQ
Children’s Sleep Habits Questionnaire
CSM
clinical supply manager
CSR
clinical study report
C-SSRS
Columbia-Suicide Severity Rating Scale
CTA
clinical trial administrator
CTM
clinical trial manager
CTMS
clinical trial management system


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 116 of 123
Abbreviation
Definition
DB
database
DBL
database lock
DBP
diastolic blood pressure
DCRF
data change request form
DDE
drug dispensing error form
DEA
drug enforcement administration
DIA
drug information association
DIS
data integration specification
DLT
dose limiting toxicity
DM
data management
DMB
data monitoring board
DMC
data monitoring committee
DML
data management lead
DMP
data management plan
DNA
deoxyribonucleic acid
DOB
date of birth
DS
document specialist
DSG
drug safety group
DSM
drug supply management (drug distributor)
DSMB 
data safety monitoring board
DSP
data safety plan


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 117 of 123
Abbreviation
Definition
DSUR
development safety update report
DTS
data transfer specification
DVD
digital video disk
EC
ethics committee
ECD
edit check and derivation specifications
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
EMA
European medicines agency
EOS
end of study
EOT
end of treatment
ET
early termination
eTMF
electronic trial master file
EU
European Union
FA
full analysis
FDA
food and drug administration
FMP
file management plan
FPFV
first patient first visit
FPI
first patient in
GCP
good clinical practice
GMP
good manufacturing practices


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 118 of 123
Abbreviation
Definition
GPV
global pharmacovigilance
HEENT
Head, neck, eyes, ears, nose, mouth, and thoat
HR
heart rate
IB
investigator’s brochure
IC or ICF
informed consent or informed consent form
ICH
international council for harmonization 
ID
identification
IDM
independent drug monitoring
IEC
independent ethics committee
IM
investigator meeting
IMV
interim monitoring visit
IND
investigational new drug
INDSR
investigational new drug safety reports
IP
investigational product
IRB
institutional review board
IRF
inventory release file
IRR
infusion related reactions
IRT
interactive response technology
ISF
investigator site file
ITT
intent-to-treat
IVRS
interactive voice response system


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 119 of 123
Abbreviation
Definition
IWRS
interactive web response system
IxRS
interactive voice/web response system
kg
kilogram
KPI
key performance indicator
LAN
local area network
LDM
lead data manager
LMS
learning management system
LLOQ
lower limit of quantification
LOCF
last observation carried forward
LPI
last patient in
LPLV
last patient last visit
LPO
last patient out
LS
least squares
MAAP
medical affairs and pharmacovigilance teams
MAH
marketing authorization holder
MedDRA
medical dictionary for regulatory activities
mg
milligram
MHRA
medicines and healthcare products regulatory agency
MINI-KID
Mini International Neuropsychiatric Interview for Children and 
Adolescents
mL
milliliter


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 120 of 123
Abbreviation
Definition
MM
medical monitor
MMP
medical monitoring plan
MMRM
mixed effect model repeat measurement
MPH
methylphenidate
MTD
maximum tolerated dose
MVR
monitoring visit report
N
number
NA
not applicable
NCS
non-clinically significant
NF
non-functional
PD
protocol deviation
PDGP
protocol deviation guidance plan
PE
physical examination
pH
hotential hydrogen
PI
principal investigator
PIN
personal identification number
PK
pharmacokinetic
PKAP
pharmacokinetic analysis plan
PM
project manager
PMP
project management plan
PP
per-protocol


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 121 of 123
Abbreviation
Definition
PRIMS 
Premier Research information management system
PS
project specialist
PT
preferred term or Prothrombin Time
PTT
Prothrombin Thromboplastin Time
PV
pharmacovigilance
PVG
pharmacovigilance group
QA
quality assurance
QARC
quality assurance, risk and compliance
QC
quality control
QOL
quality of life
QTcF
Time between the start of the Q wave and the end of the T wave (QT 
interval) in the heart's electrical cycle, corrected for heart rate with 
Fridericia’s formula
ROT
record of training
RR
respiratory rate or relative rate
RSM
regional site monitor
SAE
serious adverse event
SAP
statistical analysis plan
SAS® 
a software system used for data analysis
SBP
systolic blood pressure
SC
study coordinator
SCR
software change request 


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 122 of 123
Abbreviation
Definition
SD
standard deviation
SDS
study design specifications
SDTM 
study data tabulation model 
SDV
source data verification
SECC 
self-evident correction conventions 
SECP 
self-evident correction plan
SF
screen failure
SFT or SFTP
secure file transfer or secure file transfer plan
SIV
site initiation visit
SLA
service level agreement
SMP
safety management plan
SOC
system organ class
SOP
standard operating procedure
SOW
statement of work
SQV
site qualification visit
SUA
start-up associate
SUSAR
suspected, unexpected, serious adverse (drug) reaction
TA
trial assistant
TEAE
treatment-emergent adverse event
TMF
trial master file
TOM
task ownership matrix


Statistical Analysis Plan, 
Sponsor KemPharm, Inc.
Protocol Number KP415.S01
PCN Number KEMP7419
AD-ST-33.05 Effective date: 22-Jan-2018
Version 0.1    |
07-Jun-2018    |    AD-PR-109.01  Effective date: 26-Jun-2017
Page 123 of 123
Abbreviation
Definition
TSH
thyroid stimulating hormone
UAT
user acceptance testing
USA
United States of America
UTC
universal coordinated time
VC
variance components
WAN
wide area network
WAR
work at risk
WG
working guideline
WHO
world health organization
WHO-DD
world health organization drug dictionary
WHO-DDE
world health organization drug dictionary enhanced

Prot_001.pdf: 
 
Protocol KP415.S01 Amendment #3 
CONFIDENTIAL 
KemPharm, Inc. 
 
This confidential information about the investigational product is provided for the exclusive 
use of investigators of this product and is subject to recall at any time. The information in 
this document may not be disclosed unless federal or state law or regulations require such 
disclosure. Subject to the foregoing, this information may be disclosed only to those persons 
involved in the study who have a need to know, with the obligation not to further disseminate 
this information. 
 
 
 
 
May 09, 2019 
 
 
A Multicenter, Dose-Optimized, Open-Label Safety 
Study with KP415 in Children with Attention-
Deficit/Hyperactivity Disorder 
 
 
 
 
 
 
Protocol No: KP415.S01 
Original Protocol dated: January 13, 2018 
Amendment #1 dated: April 16, 2018 
Amendment #2 dated: April 26, 2018 
Amendment #3 dated: May 09, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




Protocol KP415.S01 Amendment #3 
CONFIDENTIAL 
KemPharm, Inc. 
 
 
Page 3 of 97 
 
May 09, 2019 
 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ...................................................................................................... 7 
PROTOCOL SYNOPSIS ............................................................................................................. 9 
1. 
SCHEDULE OF EVENTS ................................................................................................. 28 
1.1. 
Screening (all subjects) and Dose Optimization Phase (new subjects only) ................ 28 
1.2. 
Treatment Phase (First 6 Months; All Subjects) ........................................................... 32 
1.3. 
Treatment Phase (Second 6 Months), and Early Termination and Follow-Up Visits (All 
Subjects) .................................................................................................................................... 34 
2. 
BACKGROUND ................................................................................................................. 38 
2.1. 
Attention-Deficit Hyperactivity Disorder (ADHD) ...................................................... 38 
2.2. 
KP415: A Prodrug Conjugate of d-Methylphenidate ................................................... 38 
3. 
OVERVIEW OF CLINICAL STUDIES WITH KP415 ................................................. 39 
3.1. 
Study KP415.101 .......................................................................................................... 39 
3.2. 
Study KP415.109 .......................................................................................................... 40 
4. 
STUDY RATIONALE ........................................................................................................ 41 
5. 
STUDY OBJECTIVES ....................................................................................................... 41 
5.1. 
Primary Objective ......................................................................................................... 41 
5.2. 
Secondary Objectives.................................................................................................... 42 
6. 
INVESTIGATIONAL PLAN ............................................................................................ 42 
6.1. 
Study Design ................................................................................................................. 42 
6.1.1. 
Definition of “Rolled-Over Subjects” or “New Subjects” ................................................ 42 
6.1.2. 
Study Participation ............................................................................................................ 43 
6.1.3. 
Study Phases and Treatment ............................................................................................. 43 
6.2. 
Study Duration .............................................................................................................. 44 
7. 
SUBJECT SELECTION .................................................................................................... 44 
7.1. 
Number of Subjects....................................................................................................... 44 
7.2. 
Study Population ........................................................................................................... 45 
7.2.1. 
Inclusion Criteria for Subjects Rolled Over from Study KP415.E01 ............................... 45 
7.2.2. 
Inclusion Criteria for New Subjects .................................................................................. 46 
7.2.3. 
Exclusion Criteria for Subjects Rolled Over from Study KP415.E01 .............................. 48 
7.2.4. 
Exclusion Criteria for New Subjects ................................................................................. 49 
7.2.5. 
Eligibility Criteria for Treatment Phase ............................................................................ 52 
8. 
STUDY TREATMENTS .................................................................................................... 52 
8.1. 
KP415 Dose Optimization (new subjects only) ............................................................ 52 
8.2. 
Study Drug Administration in the Treatment Phase ..................................................... 53 
8.3. 
Treatment Assignment .................................................................................................. 53 
8.4. 
Blinding......................................................................................................................... 53 
8.5. 
Compliance ................................................................................................................... 53 
8.6. 
Study Stopping Rules .................................................................................................... 54 
9. 
STUDY PROCEDURES .................................................................................................... 54 
9.1. 
Screening Procedures (Visit 1A - New Subjects Only) ................................................ 54 


Protocol KP415.S01 Amendment #3 
CONFIDENTIAL 
KemPharm, Inc. 
 
 
Page 4 of 97 
 
May 09, 2019 
 
9.2. 
Screening Procedures (Visit 1B - Rolled-Over Subjects Only) .................................... 57 
9.3. 
Dose Optimization Phase (Visit 2-4; New Subjects Only) ........................................... 59 
9.3.1. 
Visit 2 ................................................................................................................................ 59 
9.3.2. 
Visit 3 (Day 7 ±3 days) ..................................................................................................... 61 
9.3.3. 
Visit 4 (Day 14 ±3 days) ................................................................................................... 62 
9.4. 
Treatment Phase (Visits 5 to 17; All Subjects) ............................................................. 63 
9.4.1. 
Visit 5 ................................................................................................................................ 63 
9.4.2. 
Treatment During At Home Periods ................................................................................. 65 
9.4.3. 
Visit 6 through Visit 16 .................................................................................................... 65 
9.4.4. 
Visit 17 (EOT Visit) ......................................................................................................... 67 
9.5. 
Unscheduled Visits ....................................................................................................... 68 
9.6. 
Early Termination Visit ................................................................................................ 69 
9.7. 
Follow-Up Visit ............................................................................................................ 70 
9.8. 
End of Study (EOS) ...................................................................................................... 71 
10. 
CONCOMITANT MEDICATIONS AND RESTRICTIONS .................................... 71 
10.1. Medication Restrictions for Rolled-Over Subjects ....................................................... 71 
10.2. Medication Restrictions for New Subjects ................................................................... 72 
10.3. Birth Control ................................................................................................................. 73 
11. 
INVESTIGATIONAL PRODUCT................................................................................ 74 
11.1. Active Pharmaceutical Ingredients ............................................................................... 74 
11.2. Clinical Trial Material................................................................................................... 74 
11.3. Pharmaceutical Formulation ......................................................................................... 75 
11.4. Packaging and Labeling ................................................................................................ 75 
11.4.1. 
Dose Optimization Phase .................................................................................................. 75 
11.4.2. 
Treatment Phase ................................................................................................................ 76 
11.5. Dispensing and Drug Return Procedures ...................................................................... 76 
11.5.1. 
General Dispensing and Drug Return Procedures ............................................................ 76 
11.5.2. 
Dispensing in Dose Optimization Phase (Visit 2, 3, and 4) .............................................. 76 
11.5.3. 
Dispensing in Treatment Phase (Visits 5 to 16) ................................................................ 77 
11.5.4. 
Dispensing at Unscheduled Visits .................................................................................... 77 
11.6. Storage of Study Drug .................................................................................................. 77 
11.7. Study Drug Accountability ........................................................................................... 78 
12. 
SAFETY AND EFFICACY ASSESSMENTS .............................................................. 78 
12.1. Medical History ............................................................................................................ 78 
12.2. Physical Examination.................................................................................................... 78 
12.3. ADHD Diagnosis and Severity Assessments ............................................................... 78 
12.4. Children’s Sleep Habits Questionnaire (CSHQ) ........................................................... 79 
12.5. Columbia-Suicide Severity Rating Scale (C-SSRS) ..................................................... 80 
12.6. Vital Signs ..................................................................................................................... 80 
12.7. 12-Lead Electrocardiogram .......................................................................................... 80 
12.8. Clinical Laboratory Measurements ............................................................................... 80 
12.9. Pregnancy Test .............................................................................................................. 81 
12.10. Adverse Event Assessments ......................................................................................... 82 
13. 
DISCONTINUATION AND REPLACEMENT OF SUBJECTS .............................. 82 
13.1. Withdrawal of Subjects from the Study ........................................................................ 82 
13.2. Replacement of Subjects ............................................................................................... 83 


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14. 
STUDY ENDPOINTS ..................................................................................................... 83 
14.1. Safety Endpoints ........................................................................................................... 83 
14.2. Efficacy Endpoints ........................................................................................................ 84 
14.3. Sleep Behavior Endpoint .............................................................................................. 84 
15. 
STATISTICAL CONSIDERATIONS .......................................................................... 84 
15.1. Sample Size Calculation ............................................................................................... 84 
15.2. Populations for Analysis ............................................................................................... 84 
15.3. Statistical Analyses ....................................................................................................... 85 
15.3.1. 
General Approach ............................................................................................................. 85 
15.3.2. 
Attrition ............................................................................................................................. 85 
15.3.3. 
Drug Exposure and Dosing Pattern................................................................................... 85 
15.3.4. 
Primary Endpoint Analysis (Safety in the Treatment Phase) ........................................... 86 
15.3.5. 
Secondary Endpoint Analyses (Efficacy and CSHQ in the Treatment Phase) ................. 86 
15.3.6. 
Descriptive Analyses (Safety and Efficacy in the Dose Optimization Phase) .................. 86 
15.3.7. 
Abuse Potential Safety Analyses ...................................................................................... 86 
15.3.8. 
Baseline Descriptive Statistics .......................................................................................... 87 
15.3.9. 
Planned Interim Analysis .................................................................................................. 87 
15.3.10. 
Subgroup Analyses ........................................................................................................... 87 
15.3.11. 
Tabulation of Individual Participant Data ......................................................................... 87 
15.3.12. 
Exploratory Analyses ........................................................................................................ 87 
16. 
ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION ................... 88 
16.1. Adverse Events ............................................................................................................. 88 
16.1.1. 
Recording and Monitoring of Adverse Events ................................................................. 88 
16.1.2. 
Definition .......................................................................................................................... 88 
16.1.3. 
AE Grading ....................................................................................................................... 88 
16.1.4. 
AE Relationship to Study Drug ........................................................................................ 89 
16.2. Serious Adverse Events ................................................................................................ 89 
16.2.1. 
Serious Adverse Event Reporting ..................................................................................... 89 
16.3. Adverse Event Treatment and Follow-Up .................................................................... 91 
16.4. Overdosage ................................................................................................................... 91 
17. 
PREGNANCY ................................................................................................................. 91 
18. 
PROTOCOL VIOLATIONS ......................................................................................... 92 
19. 
DATA MANAGEMENT AND RECORD KEEPING................................................. 92 
19.1. Data Management ......................................................................................................... 92 
19.2. Record Keeping ............................................................................................................ 93 
19.3. Access to Source Data/Documents ............................................................................... 93 
20. 
QUALITY CONTROL AND QUALITY ASSURANCE ............................................ 93 
21. 
ETHICS AND GOOD CLINICAL PRACTICE COMPLIANCE ............................. 93 
22. 
INSURANCE ................................................................................................................... 93 
23. 
COMPLETION OF STUDY .......................................................................................... 94 
24. 
STUDY ADMINISTRATIVE INFORMATION ......................................................... 94 
24.1. Protocol Amendments ................................................................................................... 94 
25. 
REFERENCES ................................................................................................................ 95 


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Appendix A: Instructions for Oral Administration of Study Drug ....................................... 97 
 
 
 


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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ADHD 
Attention-deficit hyperactivity disorder 
ADHD-RS-5 
Attention-deficit hyperactivity disorder rating scale 5 
ADL 
Activity of Daily Living 
ALT 
Alanine transaminase 
AST 
Aspartate transaminase 
AUC 
Area under the plasma concentration-time curve 
β-hCG 
Beta human chorionic gonadotropin 
BLQ 
Below the limit of quantification 
BMI 
Body Mass Index 
CBT 
Cognitive Behavioral Therapy 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CGI-S 
Clinical Global Impressions–Severity 
CGI-I 
Clinical Global Impressions–Improvement 
CI 
Confidence Interval 
Cmax 
Maximum observed plasma concentration 
CNS 
Central nervous system 
CRO 
Contract Research Organization 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CSHQ 
Children’s Sleep Habits Questionnaire 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of Variation 
DEA 
Drug Enforcement Agency 
DMDD 
Disruptive Mood Dysregulation Disorder 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EOS 
End of Study  
ER 
Extended Release 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEE 
Generalized Estimation Equation 
HIPAA 
Health Insurance Portability and Accountability Act 
HPMC 
Hydroxypropyl methylcellulose 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
IP 
Investigational Product 
IR 
Immediate Release 
IRB 
Institutional Review Board 


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ITT 
Intent-to-Treat 
IUD 
Intrauterine device 
LLN 
Lower Limit of Normal 
LS 
Least-square 
MedDRA 
Medical Dictionary of Regulatory Activities 
MAO 
Monoamine Oxidase 
MINI-KID 
Mini International Neuropsychiatric Interview for Children and Adolescents 
MPH 
Methylphenidate 
NCE 
New Chemical Entity 
ODD 
Oppositional Defiant Disorder 
OTC 
Over the Counter 
PK 
Pharmacokinetic 
PP 
Per-Protocol 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
Q1 
25th Percentile (1st Quartile) 
Q3 
75th Percentile (3rd Quartile) 
QTcF 
Time between the start of the Q wave and the end of the T wave (QT interval) in 
the heart's electrical cycle, corrected for heart rate with Fridericia’s formula 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOE 
Schedule of Events 
SNRI 
Serotonin Norepinephrine Reuptake Inhibitor 
SSRI 
Selective Serotonin Reuptake Inhibitor 
T1/2 
Apparent plasma terminal elimination half-life 
TEAE 
Treatment-Emergent Adverse Event 
TSH 
Thyroid Stimulating Hormone 
ULN 
Upper Limit of Normal 
Tmax 
Time to achieve the maximum observed plasma concentration 
 
 


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PROTOCOL SYNOPSIS 
TITLE 
A Multicenter, Dose-Optimized, Open-Label Safety Study 
with KP415 in Children with Attention-Deficit/Hyperactivity 
Disorder 
SPONSOR 
KemPharm, Inc. 
PROTOCOL NUMBER 
KP415.S01 
INVESTIGATIONAL 
PRODUCT 
The KP415 product (capsule) contains KP415 (a prodrug of 
d-methylphenidate, d-MPH) and immediate-release d-MPH. 
NAME OF ACTIVE 
INGREDIENT 
The chemical name of the KP415 prodrug is 3-(((S)-1-
carboxy-2-hydroxyethyl)carbamoyl)-1-((((R)-2-((R)-2-
methoxy-2-oxo-1-phenylethyl)piperidine-1-
carbonyl)oxy)methyl)pyridine-1-ium chloride (single d-
methylphenidate molecule covalently attached via a 
carbamate bond to a methylene oxide linker which in turn is 
connected to the nitrogen of the pyridine ring of a nicotinoyl-
serine moiety). 
ROUTE 
Oral 
NUMBER OF SITES 
Approximately 20 sites in the United States of America 
STUDY DESIGN 
The study is a multicenter, dose-optimized, open-label safety 
study with KP415 in children with Attention-
Deficit/Hyperactivity Disorder (ADHD). 
 
Eligible subjects for the current study will be either subjects 
who completed Study KP415.E01 or new subjects who did 
not previously receive KP415. 
 
Study participation: 
  
• Rolled-Over Subjects: For subjects rolled over from Study 
KP415.E01, the study will consist of a Screening Phase, 
Treatment Phase and a Follow-Up Visit. These subjects 
will be enrolled in the Screening Phase of the current 
study within 45 days after the last dose of study drug in 
Study KP415.E01. The roll-over window, dose-to-dose 
between both studies (i.e., gap between the last dose in 
Study KP415.E01 [Visit 6] and the first dose in the current 
study [Visit 5]) is maximum 45 days. Subjects are allowed 
to enter Screening (Visit 1B) on the same day as the 
Follow-Up Visit in Study KP415.E01, or later. Subjects 
not rolled over from Study KP415.E01 within 45 days of 
the last dose of study drug, may be enrolled in the current 
study as new subjects (they will need to start with 
Screening followed by the Dose Optimization Phase – see 


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New Subjects below). These subjects will be considered 
new subjects and will undergo all the visits and 
procedures of new subjects (starting with Visit 1A as the 
Screening Visit). For roll-over subjects, the Investigator 
has the option to use the clinical chemistry and 
hematology results from the Follow-Up Visit in Study 
KP415.E01 (Visit 7) in lieu of collecting new blood 
samples at Screening (Visit 1B) in the current study, as 
long as the clinical chemistry and hematology data from 
the E01 study were collected within 30 days of Screening 
(Visit 1B) in the current study. For all roll-over subjects 
who are children of childbearing potential, a blood sample 
for the measurement of a serum pregnancy test is needed 
at Visit 1B. For other assessments required at Visit 1B (C-
SSRS, for example), the Visit 7 assessments from the E01 
study (if collected) can be used as long as Visit 1B is 
conducted on the same day as Visit 7 in the E01 study. 
• New Subjects: For new subjects (not previously treated 
with KP415 during the last 45 days), the study will consist 
of a Screening Period, a Dose Optimization Phase, a 
Treatment Phase and a Follow-Up Visit. The study design 
and procedures in the Treatment Phase and Follow-Up 
Visit are the same for new subjects and rolled-over 
subjects. 
 
All subjects will receive unblinded (open-label) active 
drug in all phases of the study wherein study drug is 
administered. 
 
The phases of the study are as follows: 
• Screening Period: New Subjects will undergo a screening 
period up to 30 days prior to entering into the Dose 
Optimization Phase. Rolled-over subjects will undergo a 
screening period up to 30 days prior to entering into the 
Treatment Phase. 
• Dose Optimization Phase (for new subjects only): 
During the Dose Optimization Phase, subjects will be 
titrated to doses of 20, 30, or 40 mg KP415 capsules based 
on individual tolerability and best dose-response in the 
opinion of the Investigator. 
• Treatment Phase: Eligible subjects will receive single 
daily doses of KP415 for 360 ±20 days, approximately 12 
months. The starting dose of KP415 given in the 
Treatment Phase will be the same as the optimized dose of 


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KP415 in Study KP415.E01 for rolled-over subjects or at 
the end of the Dose Optimization Phase for new subjects. 
During the Treatment Phase, the dose of KP415 may be 
changed based on individual tolerability and best dose-
response (to either 20, 30, or 40 mg KP415 capsules). 
Safety, efficacy and sleep behavior assessments will be 
performed. After subjects complete approximately 180 
days (approximately 6 months) of the Treatment Phase, an 
interim analysis will be conducted to evaluate safety 
parameters. 
• Follow-Up Visit: 3 ±2 days after administration of the last 
dose of the Treatment Phase, subjects will enter a Follow-
Up Visit to evaluate safety parameters. 
STUDY STOPPING 
RULES 
The study will be stopped for any of the following reasons, 
whichever comes first: 
1. An interim analysis of the safety data will be 
conducted after approximately all subjects remaining 
in the study have completed 180 days (approximately 
6 months) of treatment. After the completion of the 
interim analysis, based on the acceptance of the 
clinical and nonclinical safety database from the 
current study and other studies, the Sponsor may stop 
the study. Treatment in the current study will continue 
as planned while the interim analysis is conducted. If 
the decision is made to stop the study, all subjects 
remaining in the study will undergo the EOT Visit 
(with safety evaluations including fasting safety labs 
and ECGs) and a Follow-Up Visit. 
2. After all subjects have completed 360 days 
(approximately 1 year) of treatment.  
PRIMARY OBJECTIVE 
To determine the safety and tolerability of KP415 in treating 
children with ADHD. 
SECONDARY 
OBJECTIVES 
To determine efficacy and changes in sleep behavior during 
KP415 treatment in children with ADHD. 
NUMBER OF SUBJECTS 
Approximately 250 subjects will be enrolled in the Treatment 
Phase of the study. Subjects will be rolled over from Study 
KP415.E01 and to reach the targeted number of subjects, new 
subjects will be enrolled as well. Subjects who fail Screening 
and new subjects who terminate early during the Dose 
Optimization Phase may be replaced. Subjects who terminate 
early in the Treatment Phase will not be replaced. 
SUBJECT SELECTION 
CRITERIA 
Inclusion Criteria for Subjects Rolled Over from Study 
KP415.E01 (at Screening Visit 1B, except when noted 
otherwise) 
1. 
Subjects must have completed the Double-Blind 
Treatment Phase of Study KP415.E01, and must have 


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received the last dose of KP415 in Study KP415.E01 
(Visit 6) within 45 days prior to the first dose in the 
current study (Visit 5). Subjects who completed 
Study KP415.E01 but received their last dose of 
study drug more than 45 days prior to Visit 5 are 
eligible in the current study as New Subjects (but not 
as rolled-over subjects). Subjects who completed 
Study KP415.E01 and start the current study outside 
the 45-day roll-over window will be considered New 
Subjects and will undergo all the visits and 
procedures of new subjects (starting with Visit 1A as 
the Screening Visit). 
2. 
Subjects rolled-over from Study KP415.E01 needed 
to be at least 6 years old and less than 13 years old at 
the start of the Dose Optimization Phase in Study 
KP415.E01. By the time they are rolled over into the 
current study, some may be 13 years old. 
3. 
Female subjects must agree, when they are of 
childbearing potential at Screening or when they 
become of childbearing potential during the study, to 
remain abstinent or agree to use an effective and 
medically acceptable form of birth control from the 
time of written or verbal assent to at least 14 days 
after the last dose of study drug has been taken. 
Male subjects with female partners must agree, when 
their partners are of childbearing potential at 
Screening or when their partners become of 
childbearing potential during the study, to remain 
abstinent or agree to use an effective and medically 
acceptable form of birth control from the time of 
written or verbal assent to at least 14 days after the 
last dose of study drug has been taken. Childbearing 
potential is defined as follows: Girls under the age of 
12 who have not had their first period will be 
considered “not of child-bearing potential”. Girls of 
12 years and older (including girls who will become 
12 years or older during the study) will be considered 
“of child-bearing potential”, even if they have not yet 
had their first period. Irrespective of age, girls who 
have had their first period, will be considered “of 
child-bearing potential”. 
4. 
Subject must be in general good health defined as the 
absence of any clinically relevant abnormalities as 
determined by the Investigator based on physical and 
neurological examinations, vital signs, ECGs, 
medical history, and clinical laboratory values 


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(hematology, chemistry, and urinalysis) at the 
Follow-Up Visit of Study KP415.E01. If any of the 
hematology, chemistry, or urinalysis results are not 
within the laboratory's reference range, then the 
subject can be included only if the Investigator 
determines the deviations to be not clinically 
relevant. 
5. 
At least one parent/legal guardian of the subject must 
voluntary give written permission for him/her to 
participate in the study. 
6. 
Subject must give written or verbal assent prior to 
study participation. For verbal assent, the procedure 
will be documented and signed by a witness. A parent 
or guardian may not be the witness for a child's 
verbal assent document. 
7. 
Subject must be able and willing to wash out current 
stimulant ADHD medications (if applicable, if taking 
ADHD medications between studies), including 
herbal medications from 5 days prior to the start of 
the Treatment Phase (Visit 5), and abstain from 
taking these to the end of the Follow-Up Visit or 
Early Termination; and wash out non-stimulant 
ADHD medications (if applicable) from 14 days prior 
to the start of the Treatment Phase (Visit 5), and 
abstain from taking these to the end of the Follow-Up 
Visit or Early Termination. 
8. 
Subject, subject’s parent/legal guardian and caregiver 
(if applicable) must understand and be willing and 
able to comply with all study procedures and visit 
schedule. If the subject is cared for by a caregiver for 
relevant parts of any period between study visits, and 
if in this case, in the opinion of the Investigator, the 
caregiver of the subject is more suitable for certain 
assessments, the caregiver will need to agree to the 
applicable procedures and visits. 
9. 
Subject, parent/legal guardian and caregiver (if 
applicable) must be able to speak and understand 
English, and be able to communicate satisfactorily 
with the Investigator and study coordinator. 
10. 
Subject must be able to swallow size 3 capsules as 
demonstrated by easily swallowing a size 3 placebo 
capsule at Screening, unless the subject participated 
in the KP415.E01 study previously, or unless the 
subject agrees to take the contents of the capsule 


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sprinkled on a small amount of applesauce or in a 
small amount of water. 
 
Inclusion Criteria for New Subjects (at Screening Visit 
1A, except when noted otherwise) 
1. 
Subject must be at least 6 years old and less than 13 
years old at the start of the Dose Optimization Phase 
(Visit 2). 
2. 
Subject must have a body weight of at least 21 kg at 
Screening. 
3. 
Female subjects must agree, when they are of 
childbearing potential at Screening or when they 
become of childbearing potential during the study, to 
remain abstinent or agree to use an effective and 
medically acceptable form of birth control from the 
time of written or verbal assent to at least 14 days 
after the last dose of study drug has been taken. 
Male subjects with female partners must agree, when 
their partners are of childbearing potential at 
Screening or when their partners become of 
childbearing potential during the study, to remain 
abstinent or agree to use an effective and medically 
acceptable form of birth control from the time of 
written or verbal assent to at least 14 days after the 
last dose of study drug has been taken. Childbearing 
potential is defined as follows: Girls under the age of 
12 who have not had their first period will be 
considered “not of child-bearing potential”. Girls of 
12 years and older (including girls who will become 
12 years or older during the study) will be considered 
“of child-bearing potential”, even if they have not yet 
had their first period. Irrespective of age, girls who 
have had their first period, will be considered “of 
child-bearing potential”. 
4. 
Subject must be in general good health defined as the 
absence of any clinically relevant abnormalities as 
determined by the Investigator based on physical and 
neurological examinations, vital signs, ECGs, 
medical history, and clinical laboratory values 
(hematology, chemistry, and urinalysis) at Screening. 
If any of the hematology, chemistry, or urinalysis 
results are not within the laboratory's reference range, 
then the subject can be included only if the 
Investigator determines the deviations to be not 
clinically relevant. 


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5. 
At least one parent/legal guardian of the subject must 
voluntary give written permission for him/her to 
participate in the study. 
6. 
Subject must give written or verbal assent prior to 
study participation. For verbal assent, the procedure 
will be documented and signed by a witness. A parent 
or guardian may not be the witness for a child's 
verbal assent document. 
7. 
Subject must meet Diagnostic and Statistical Manual 
of Mental Disorders - Fifth Edition (DSM-5) criteria 
for a primary diagnosis of ADHD (combined, 
inattentive, or hyperactive/impulsive presentation) 
per clinical evaluation and confirmed by the Mini 
International Neuropsychiatric Interview for Children 
and Adolescents (MINI-KID). If the MINI-KID 
assessment is available from a previous study with 
KP415, it does not need to be repeated. 
8. 
Subject must have a score of at least 3 (mildly ill) on 
the clinician-administered Clinical Global 
Impressions–Severity (CGI-S) scale at Visit 2. For 
subjects requiring washout of ADHD medications, 
this criterion refers to a score following washout. 
9. 
Subject must be able and willing to wash out current 
stimulant ADHD medications, including herbal 
medications from 5 days prior to the start of the Dose 
Optimization Phase (Visit 2), and abstain from taking 
these to the end of the Follow-Up Visit or Early 
Termination; and wash out non-stimulant ADHD 
medications from 14 days prior to the start of the 
Dose Optimization Phase (Visit 2), and abstain from 
taking these to the end of the Follow-Up Visit or 
Early Termination. 
10. 
An ADHD-Rating Scale-5 (ADHD-RS-5) total score 
of at least 28 at Visit 2. For subjects requiring 
washout of ADHD medications, this criterion refers 
to a score following washout. 
11. 
Subject, subject’s parent/legal guardian and caregiver 
(if applicable) must understand and be willing and 
able to comply with all study procedures and visit 
schedule. If the subject is cared for by a caregiver for 
relevant parts of a school day, and if in this case, in 
the opinion of the Investigator, the caregiver of the 
subject is more suitable for certain assessments, the 
caregiver will need to agree to the applicable 
procedures and visits. 


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12. 
Subject, parent/legal guardian and caregiver (if 
applicable) must be able to speak and understand 
English, and be able to communicate satisfactorily 
with the Investigator and study coordinator. 
13. 
Subject must be able to swallow size 3 capsules as 
demonstrated by easily swallowing a size 3 placebo 
capsule at Screening, unless the subject participated 
in the KP415.E01 study previously, or unless the 
subjects agrees to take the contents of the capsule 
sprinkled on a small amount of apple sauce or in a 
small amount of water. 
 
Exclusion Criteria for Subjects Rolled Over from Study 
KP415.E01 (at Screening Visit 1B, except when noted 
otherwise) 
1. 
If female, must not be pregnant or breastfeeding, and 
if of childbearing potential, must have a negative 
pregnancy test at the start of the Screening Phase 
(Visit 1B). In addition, a positive pregnancy test 
before the last dose of study drug will exclude a 
subject from further participation in the study. “Of 
childbearing potential” is defined in Section 12.9. 
2. 
Based on the medical history evaluated at Screening 
(Visit 1B), subject with any new clinically significant 
chronic medical condition that, in the judgment of the 
Investigator, may interfere with the participant's 
ability to participate in the study, or that may affect 
safety and/or the results of the study. 
3. 
In the opinion of the Investigator, subject has 
clinically significant suicidal ideation/behavior, based 
on history of attempted suicide and the C-SSRS 
assessment at Screening or at any time before the last 
dose of study drug. 
4. 
Subjects are using or planning to use prohibited drugs 
during the trial as specified in the protocol. 
5. 
Subject has a positive urine MPH screen at Visit 5. 
6. 
Subject, parent/legal guardian and caregiver (if 
applicable at the Investigator’s discretion) has 
commitments during the study that would interfere 
with attending study visits. 
7. 
Subject or subject's family anticipates a move outside 
the geographic range of the investigative site during 
the study period, or plans extended travel inconsistent 
with the recommended visit interval during study 
duration. 


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8. 
Subject is, in the opinion of the Investigator, 
unsuitable in any other way to participate in this 
study. 
 
Exclusion Criteria for New Subjects (at Screening Visit 
1A, except when noted otherwise) 
1. 
Subjects who have received study drug (KP415 or 
placebo for KP415) in Study KP415.E01 during the 
45 days prior to the Treatment Phase. Subjects who 
have received KP415 in Study KP415.E01 less than 
45 days prior to the Treatment Phase are eligible to 
be enrolled in the current study as roll-overs (but not 
as new subjects). 
2. 
If female, must not be pregnant or breastfeeding, and 
if of childbearing potential, must have a negative 
pregnancy test at the start of the Screening Phase 
(Visit 1A). In addition, a positive pregnancy test 
before the last dose of study drug will exclude a 
subject from further participation in the study. “Of 
childbearing potential” is defined in Section 12.9. 
3. 
Subject with any clinically significant chronic 
medical condition that, in the judgment of the 
Investigator, may interfere with the participant's 
ability to participate in the study. 
4. 
Subject has any diagnosis of bipolar I or II disorder, 
major depressive disorder, conduct disorder, 
obsessive-compulsive disorder, any history of 
psychosis, autism spectrum disorder, disruptive mood 
dysregulation disorder (DMDD), intellectual 
disability, Tourette's Syndrome, confirmed genetic 
disorder with cognitive and/or behavioral 
disturbances. Subjects with oppositional defiant 
disorder (ODD) are permitted to enroll in the study as 
long as ODD is not the primary focus of treatment, 
and, in the opinion of the Investigator, the ODD is 
mild to moderate, and eligible subjects with ODD are 
appropriate and cooperative during Screening. 
5. 
Subject has generalized anxiety disorder or panic 
disorder that has been the primary focus of treatment 
at any time during the 12 months prior to Screening 
or that has required pharmacotherapy any time during 
the 6 months prior to Screening. 
6. 
Subject has evidence of any chronic disease of the 
central nervous system (CNS) such as tumors, 
inflammation, seizure disorder, vascular disorder, 


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potential CNS related disorders that might occur in 
childhood (e.g., Duchenne Muscular dystrophy, 
myasthenia gravis, or other neurologic or serious 
neuromuscular disorders), or history of persistent 
neurological symptoms attributable to serious head 
injury. A past history of febrile seizure, drug-induced 
seizure, or alcohol withdrawal seizure is allowed. 
Subject taking anticonvulsants for seizure control 
currently or within the past 2 years before Screening 
are not eligible for study participation. 
7. 
Subject has a current (last month) psychiatric 
diagnosis other than specific phobia, motor skills 
disorders, oppositional defiant disorder, sleep 
disorders, elimination disorders, adjustment 
disorders, learning disorders, or communication 
disorders. Subjects allowed to enroll with any of 
these DSM disorders will require written justification 
from the Investigator documenting why the 
conditions will not interfere with participation and to 
emphasize that ADHD is the primary indication. 
8. 
In the opinion of the Investigator, subject has 
clinically significant suicidal ideation/behavior, based 
on history of attempted suicide and the C-SSRS 
assessment at Screening or at any time before the last 
dose of study drug. 
9. 
Subject has any clinically significant unstable 
medical abnormality, chronic disease, or a history of 
a clinically significant abnormality of the 
cardiovascular (including cardiomyopathy, serious 
arrhythmias, structural cardiac disorders, or severe 
hypertension), gastrointestinal, respiratory, hepatic, 
or renal systems, or a disorder or history of a 
condition (e.g., malabsorption, gastrointestinal 
surgery) that may interfere with drug absorption, 
distribution, metabolism, or excretion of study drug. 
Active medical conditions that are minor or well-
controlled are not exclusionary if they do not affect 
risk to the subject or the study results. In cases in 
which the impact of the condition upon risk to the 
subject or study results is unclear, the medical 
monitor should be consulted. Any subject with a 
known cardiovascular disease or condition (even if 
controlled) must be discussed with the medical 
monitor during Screening. 


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10. 
Subject has a history or presence of abnormal ECGs, 
which in the Investigator's opinion is clinically 
significant. 
11. 
Subject has a history of, or currently has a 
malignancy, except for non-melanomatous skin 
cancer. 
12. 
Subject has uncontrolled thyroid disorder as 
evidenced by thyroid stimulating hormone (TSH) 
≤0.8 x the lower limit of normal (LLN) or ≥1.25 x the 
upper limit of normal (ULN) for the reference 
laboratory at Screening. For subjects who previously 
participated in Study KP415.E01, this condition does 
not need to be re-evaluated. 
13. 
Subjects with a history of substance abuse or 
treatment (including alcohol) within 1 year prior to 
Screening. 
14. 
Subject shows evidence of substance or alcohol use 
or is currently using tobacco or other nicotine-
containing products, or has a positive urine alcohol or 
urine drug screen at Screening. Subjects with a 
positive urine drug screen may be allowed to 
continue in the study, provided that the Investigator 
determines that the positive test is a result of taking 
prescribed medications, and subject is willing to wash 
out the current medication as required. 
15. 
Subject has participated in any other clinical study 
with an investigational drug/product within 90 days 
prior to Screening, or is currently participating in 
another clinical trial, with the exception of any trial 
with KP415, as follows: Subjects who participated in 
Study KP415.E01 and completed the last dose in 
Study KP415.E01 more than 45 days before the 
Treatment Phase in the current study, are eligible as 
new subjects in the current study. Subjects who 
completed other studies with KP415 (for example, the 
single-dose pharmacokinetic study KP415.105) may 
be enrolled in the current study as new subjects after a 
minimum 5-day washout period between the last dose 
of KP415 and Screening in the current study. 
16. 
Subject has taken ADHD medications from more than 
one class within 30 days prior to Screening. Subjects 
on a stable dose of one ADHD medication with 
occasional use of ADHD medications from another 
class are eligible at the discretion of the Investigator. 
17. 
Subjects with demonstrated lack of response or 


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intolerability to adequate dose and duration of 
treatment with methylphenidate products. Judgment of 
adequate dose and duration is at the discretion of the 
Investigator.  
18. 
Subjects are using or planning to use prohibited drugs 
during the trial as specified in the protocol. 
19. 
Subject has a positive urine MPH screen at Visit 2. 
20. 
Subject has a history of severe allergies or adverse 
drug reactions to more than one class of medications. 
21. 
Subject has a history of allergic reaction or a known 
or suspected sensitivity to methylphenidate or any 
substance that is contained in the study drug. 
22. 
Subject, parent/legal guardian and caregiver (if 
applicable at the Investigator’s discretion) has 
commitments during the study that would interfere 
with attending study visits. 
23. 
Subject or subject's family anticipates a move outside 
the geographic range of the investigative site during 
the study period, or plans extended travel inconsistent 
with the recommended visit interval during study 
duration. 
24. 
Subject is, in the opinion of the Investigator, 
unsuitable in any other way to participate in this 
study. 
 
Eligibility Criteria (end of Dose Optimization Phase, new 
subjects only) 
Subjects will need to meet the following additional eligibility 
criteria at the end of the Dose Optimization Phase in order to 
enter into the Treatment Phase: 
1. 
A reduction of ≥30% in ADHD-RS-5 from baseline 
(Visit 2) during the Dose Optimization Phase. 
2. 
A CGI-I score of 1 or 2 at the end of the Dose 
Optimization Phase. 
3. 
Acceptable tolerability of the optimized KP415 dose 
experienced during the Dose Optimization Phase. 
Rescreening 
New subjects who are screened outside the screening window 
may be rescreened for participation at a later time. New 
subjects who received any dose of study drug and are 
terminated early or are not eligible to continue in the 
Treatment Phase, are not eligible to participate later in the 
study (and will not be rescreened). 


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TEST PRODUCT, DOSE, 
AND ROUTE OF 
ADMINISTRATION 
The KP415 capsules contain two active pharmaceutical 
ingredients: d-methylphenidate (d-MPH) hydrochloride as the 
immediate release (IR) d-MPH component, and KP415 
prodrug as the extended release (ER) d-MPH component. In 
terms of d-MPH equivalent amounts, all capsule strengths 
contain 30% of d-MPH (IR component) and 70% of d-MPH 
from the KP415 prodrug (ER component). The total 
equivalent amount of d-MPH in each capsule strength (used 
as daily doses in this study), and the amounts of both APIs are 
listed in the following table. 
 
Total 
d-MPH 
dose 1 
(mg) 
d-MPH 2 
 
 
(mg) 
KP415 
Prodrug 3 
 
(mg) 
20 
6 
28 (14) 
30 
9 
42 (21) 
40 
12 
56 (28) 
1. Based on the d-MPH amount plus the equivalent amount of d-MPH as 
KP415 prodrug. 
2. The dose of d-MPH is expressed in terms of d-methylphenidate 
hydrochloride. 
3. The dose of KP415 prodrug is expressed in terms of KP415 chloride. 
The amount of d-MPH hydrochloride equimolar to each KP415 
prodrug dose is listed between parentheses. 
 
The KP415 prodrug is not yet a scheduled controlled 
substance; however, methylphenidate is a Schedule II 
substance under the Controlled Substances Act. As a result of 
the d-MPH content in the KP415 capsules, the drug product 
used in this study is a Schedule II product. Therefore, study 
sites are required to have the appropriate permit from the 
Drug Enforcement Agency (DEA) to receive, store, ship and 
dispense the KP415 product according to all local, state, and 
federal regulations for Schedule II substances. 
All subjects will receive unblinded (open-label) active drug in 
all phases of the study wherein study drug is administered, as 
follows: 
• In the Dose Optimization Phase (new subjects only), 
daily treatments of 20, 30 and 40 mg open-label KP415 
capsules will be administered (one capsule/day), for the 
titration to an optimal daily KP415 dose. 
• In the Treatment Phase, daily treatments of open-label 
KP415 capsules will be administered (one capsule/day), 
at a daily dose of KP415 that is the same as the optimal 
dose of KP415 at the end of the Dose Optimization 
Phase, either 20, 30, or 40 mg KP415 capsules. However, 
during the Treatment Phase, the Investigator will evaluate 


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the tolerability and dose-response on an ongoing basis, 
and based on this evaluation, may change the dose of 
KP415. At any time, the daily oral dose of KP415 will be 
either 20, 30, or 40 mg. 
 
All study drugs will be given orally with up to 210-240 mL 
water. Additional water may be given if needed. The capsule 
needs to be swallowed whole (without crushing, cutting, 
crushing, chewing, opening, or dissolving) or may be taken 
by sprinkling the contents of the capsule over a small amount 
of applesauce, or putting the contents in a small amount of 
water. 
ADHD 
SEVERITY/EFFICACY 
EVALUATION CRITERIA 
The following scales will be used to assess the changes in 
ADHD severity: 
• ADHD-Rating Scale-5 (ADHD-RS-5): The ADHD-RS-
5 is an 18-item scale (DuPaul 2016) based on Diagnostic 
and Statistical Manual of Mental Disorders, 5th edition 
(DSM-5) (American Psychiatric Association 2013) 
criteria of ADHD that rates symptoms on a 4-point 
scale. Each item is scored using a combination of 
severity and frequency ratings from a range of 0 
(reflecting no symptoms or a frequency of never or 
rarely) to 3 (reflecting severe symptoms or a frequency 
of very often), so that the total ADHD-RS-5 scores 
range from 0 to 54. The 18 items can be divided into 
two 9-item subscales: One for hyperactivity/impulsivity 
and the other for inattentiveness. Scores will be obtained 
during a clinician-directed interview with the 
parent/guardian/caregiver at each visit. 
• Clinical Global Impressions–Severity (CGI-S): The 
CGI-S is a clinician-rated scale that evaluates the 
severity of psychopathology (ADHD symptoms in the 
study) on a scale from 1 (not at all ill) to 7 (among the 
most severely ill) (Busner and Targum 2007). 
• Clinical Global Impressions–Improvement (CGI-I): The 
CGI-I is a clinician-rated scale that evaluates the 
improvement of psychopathology (ADHD symptoms in 
the study) on a scale from 1 (very much improved) to 7 
(very much worse). 
During the Dose Optimization Phase (new subjects only), the 
ADHD-RS-5, CGI-I and CGI-S scale assessments are the 
main efficacy response variables (in conjunction with 
tolerability and safety) to guide dose optimization. During 
the Treatment Phase, the ADHD-RS-5 and CGI-S scale 
assessments are the efficacy variables to evaluate the 
changes in ADHD severity over time, and may be used (in 


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conjunction with tolerability and safety) to adjust the dose of 
study drug. 
 
DURATION OF SUBJECT 
PARTICIPATION AND 
DURATION OF STUDY 
Rolled-Over Subjects: Subjects rolled over from Study 
KP415.E01 will participate in the study as outpatients for 
up to 416 days, including up to 30 days of Screening, 1 day 
for Visit 5, up to 380 days (360 ±20 days) in the Treatment 
Phase and a Follow-Up Visit up to 5 days (3 ±2 days) after 
the administration of the last dose of the Treatment Phase. 
Subjects who completed Study KP415.E01 and start the 
current study outside the 45-day roll-over window will be 
considered new subjects and will undergo all the visits and 
procedures of new subjects. The roll-over window (for 
Rolled-Over Subjects), dose-to-dose between both studies 
(i.e., gap between the last dose in Study KP415.E01 [Visit 
6] and the fist dose in the current study [Visit 5]) is 
maximum 45 days. 
 
New Subjects: New subjects will participate in the study as 
outpatients for up to 440 days including up to 30 days of 
Screening, 1 day for Visit 2, up to 23 days (20 ±3 days) in 
the Dose Optimization Phase, 1 day for Visit 5, up to 380 
days (360 ±20 days) in the Treatment Phase and a Follow-
Up Visit up to 5 days (3 ±2 days) after the administration of 
the last dose of the Treatment Phase. 
 
If the study is stopped earlier based on the study stopping 
rules, all or some subjects may participate in the study for 
shorter durations than those listed above. 
MEDICATION 
RESTRICTIONS 
Rolled-over subjects will be prohibited/limited to receive 
certain medications in the trial, as follows: 
• Stimulant ADHD medications (with the exception of 
study drug), including herbal medications, are prohibited 
from 5 days prior to the start of the Treatment Phase 
(Visit 5) to the end of the Follow-Up Visit or Early 
Termination Visit. These include: methylphenidate, 
amphetamine, Ritalin®, Ritalin® SR, Metadate® ER, 
Concerta®, dextromethylphenidate, Focalin®, 
dextroamphetamine, Dexedrine®, Adderall®. 
• Non-Stimulant ADHD medications are prohibited from 
14 days prior to the start of the Treatment Phase (Visit 5) 
to the end of the Follow-Up Visit or Early Termination 
Visit. These include: Atomoxetine, guanfacine, 
clonidine; and SSRIs such as fluoxetine and paroxetine. 
• 
The following medications are prohibited from 14 days 
prior to the start of the Treatment Phase (Visit 5) to the 


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end of the Follow-Up Visit or Early Termination Visit: 
o Tricyclic antidepressants. 
o Monoamine oxidase inhibitors (MAOIs). 
o Mood stabilizers (e.g., lithium, valproate, 
quetiapine). 
o Antipsychotics (e.g., risperidone, olanzapine). 
o Coumarin anticoagulants. 
o Anticonvulsants. 
o Halogenated anesthetics. 
o Phenylbutazone 
o Coumarin anticoagulants 
 
• 
Sedative hypnotics/sleep enhancers (with the exception of 
melatonin) are prohibited from 14 days prior to the start of 
the Treatment Phase (Visit 5) to the end of the Follow-Up 
Visit or Early Termination Visit. 
• 
Melatonin is allowed if subjects have taken it for more 
than 30 days before the start of the Treatment Phase (Visit 
5) and are on a stable dose. Otherwise, melatonin is 
prohibited from 5 days prior to the start of Visit 5 to the 
end of the Follow-Up Visit or Early Termination Visit. 
 
New subjects will be prohibited/limited to receive certain 
medications in the trial, as follows: 
• Stimulant ADHD medications (with the exception of 
study drug), including herbal medications, are prohibited 
from 5 days prior to the start of the Dose Optimization 
Phase (Visit 2) to the end of the Follow-Up Visit or Early 
Termination Visit. These include: methylphenidate, 
amphetamine, Ritalin®, Ritalin® SR, Metadate® ER, 
Concerta®, dextromethylphenidate, Focalin®, 
dextroamphetamine, Dexedrine®, Adderall®. 
• Non-Stimulant ADHD medications are prohibited from 
14 days prior to the start of the Dose Optimization Phase 
(Visit 2) to the end of the Follow-Up Visit or Early 
Termination Visit. These include: Atomoxetine, 
guanfacine, clonidine; and SSRIs such as fluoxetine and 
paroxetine. 
• 
The following medications are prohibited from 14 days 
prior to the start of the Dose Optimization Phase (Visit 2) 
to the end of the Follow-Up Visit or Early Termination 
Visit: 
o Tricyclic antidepressants. 
o Monoamine oxidase inhibitors (MAOIs). 
o Mood stabilizers (e.g., lithium, valproate, 
quetiapine). 


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o Antipsychotics (e.g., risperidone, olanzapine). 
o Coumarin anticoagulants. 
o Anticonvulsants. 
o Halogenated anesthetics. 
o Phenylbutazone 
 
• 
Sedative hypnotics/sleep enhancers (with the exception of 
melatonin) are prohibited from 14 days prior to the start of 
the Dose Optimization Phase (Visit 2) to the end of the 
Follow-Up Visit or Early Termination Visit. 
• 
Melatonin is allowed if subjects have taken it for more 
than 30 days before the start of the Dose Optimization 
Phase (Visit 2) and are on a stable dose. Otherwise, 
melatonin is prohibited from 5 days prior to Visit 2 to the 
end of the Follow-Up Visit or Early Termination Visit. 
 
Allowed medications for all enrolled subjects: 
Medications allowed during the course of the study include 
nasal steroids, bronchodilators, acetaminophen and 
nonsteroidal anti-inflammatory medications; non-sedating 
antihistamines such as cetirizine, loratadine, and 
fexofenadine; mometasone; and approved courses of 
prescription and nonprescription medications for the 
treatment of acute illnesses. 
 
If subjects participated in a previous study with KP415 
(including Study KP415.E01), they are allowed to take any 
medications (including ADHD medications) after 
completing the previous study with KP415 and before 
starting the current study, except for the medications and 
the time intervals specified in this protocol. 
SAFETY ENDPOINTS 
• The occurrence of Treatment-Emergent Adverse Events 
(TEAEs) will be assessed starting following the first dose 
of study drug, and ending with the Follow-Up Visit or 
Early Termination Visit. 
• Physical examinations will be performed at the first visit 
(at Screening, before the first dose of study drug), after 
approximately 6 months of treatment (Visit 11), and at the 
end of the Treatment Phase (Visit 17, EOT) or at Early 
Termination. 
• Clinical laboratory tests will be performed at the first visit 
(at Screening, before the first dose of study drug), after 
approximately 6 months of treatment (Visit 11), and at the 
end of the Treatment Phase (Visit 17, EOT) or at Early 
Termination. 
• ECG parameters will be collected at the first visit (at 


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Screening, before the first dose of study drug), after 
approximately 6 months of treatment (Visit 11), and at the 
end of the Treatment Phase (Visit 17, EOT) or at Early 
Termination. 
• Vital signs, height, weight, and BMI will be collected at 
each visit. 
• A C-SSRS will be performed at each study visit. 
 
EFFICACY ENDPOINTS 
During the Dose Optimization Phase (new subjects only): 
• 
CGI-S will be assessed at each visit (Screening to Visit 5). 
ADHD-RS-5 will administered at Visits 2 through 5. CGI-
I will be assessed at Visits 3, 4, and 5 (since CGI-I is an 
ADHD improvement assessment, it will not be assessed at 
Screening and at Visit 2). 
During the Treatment Phase (all subjects): 
• 
ADHD-RS-5 and CGI-S will be assessed at each visit 
(Visit 5 to Visit 17, EOT). 
 
SLEEP BEHAVIOR 
ENDPOINT 
The modified, abbreviated Children’s Sleep Habits 
Questionnaire (CSHQ) will be used to assess the sleep 
behavior in the Dose Optimization Phase for new subjects 
(Visit 2) and in the Treatment Phase for all subjects (Visit 5 to 
Visit 17). The baseline will be measured before the first dose 
of study drug, at Visit 2 for new subjects and at Visit 5 for 
roll-over subjects. 
 
ANALYSIS 
POPULATIONS 
• Treatment-Phase Safety Population: All enrolled 
subjects in the Treatment Phase who received at least one 
dose of study medication in the Treatment Phase and had 
at least one post-dose safety assessment in the Treatment 
Phase. 
• Efficacy Population: All enrolled subjects who 
received at least 30 days of study medication in the 
Treatment Phase, who had adequate data to assess the 
change from baseline of the efficacy parameters and 
who had no protocol deviations that could affect the 
efficacy parameters. 
• Dose-Optimization Safety Population: All enrolled 
subjects in the Dose Optimization Phase (“New 
Subjects”) who received at least one dose of study 
medication in the Dose Optimization Phase and had at 
least one post-dose safety assessment in the Dose 
Optimization Phase. 
STATISTICAL 
ANALYSES 
The primary focus of the statistical analyses are the safety 
assessments during the Treatment Phase. The secondary focus 
of the statistical analyses is the efficacy assessments during 


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the Treatment Phase. The safety and efficacy parameters 
during the Dose Optimization Phase (for new subjects only) 
will be summarized descriptively. 
 
Primary Endpoint (Safety in the Treatment Phase): 
The frequencies of adverse events (AEs), changes in clinical 
laboratory assessments, physical examinations, changes in 
weight, height and BMI, vital signs, ECG parameters, and the 
frequency of suicidal ideation or behavior (assessed using the 
C-SSRS) will be analyzed in the Treatment-Phase Safety 
Population. The baseline for the safety parameters will be 
measured at Visit 1A and 1B. 
 
Secondary Endpoint (Efficacy in the Treatment Phase): 
Changes in ADHD-RS-5, CGI-S and CSHQ will be analyzed 
in the Efficacy Population. The baseline for ADHD-RS-5, 
CGI-S and CSHQ will be measured at Visit 5 for roll-over 
subjects and at Visit 2 for new subjects. 
 
Descriptive Analyses (Safety and Efficacy in the Dose 
Optimization Phase): 
The safety and efficacy parameters during the Dose 
Optimization Phase (from Screening to Visit 5) will be 
summarized descriptively in the Dose-Optimization Safety 
Population. 
 
Subgroup Analyses: 
Subgroup analyses will include safety, efficacy and CSHQ 
endpoints by study site, dose (including cumulative dose), 
duration of treatment, previous treatment, age, and gender. 
STUDY PROCEDURES 
The study procedures are outlined in the Schedule of 
Events (Section 1).  


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1. SCHEDULE OF EVENTS 
1.1. Screening (all subjects) and Dose Optimization Phase (new subjects only) 
ASSESSMENTS 
NEW 
SCREENING 
PHASE 22 
ROLLOVER 
OPEN-LABEL 
DOSE OPTIMIZATION PHASE 21, 22 
(NEW SUBJECTS ONLY) 
Study Day 
-30 to 
-1 
-30 to 
-1 
0 
1-6 
(±3 
Days) 
7 
(±3 
Days) 
8-13 
(±3 
Days) 
14 
(±3 
Days) 
15-20 
(±3 
Days) 
Visit Number 
1A 
1B24 
2 
 
3 
 
4 
 
Parental Permission/Written or Verbal 
Assent 
X 
X 
 
 
 
 
 
 
ADHD Diagnosis and Confirmation 1 
X 
 
 
 
 
 
 
 
Capsule Swallowing Test 2 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
X 
X 
 
X 
 
X 
 
Demographics 
X 
X 
 
 
 
 
 
 
Medical History 3 
X 
X 
X 
 
 
 
 
 
Physical Examination 
X 
X 
 
 
 
 
 
 
Body Weight, Height, BMI 4 
X 
X 
 
 
 
 
 
 
Vital Signs 5 
X 
X 
X 
 
X 
 
X 
 
12-Lead ECG 6 
X 
X 
 
 
 
 
 
 
Chemistry/Hematology/Urinalysis 
(under fasting conditions) 
X 
X 
 
 
 
 
 
 
Urine Alcohol/Drugs of Abuse Screen 7 
X 
X 
 
 
 
 
 
 
Urine MPH Screen 8 
X 
 
X 
 
 
 
 
 
Pregnancy Test 9 
X 
X 
X 
 
 
 
 
 
C-SSRS 10 
X 
X 
X 
 
X 
 
X 
 
Washout ADHD Meds 11 
 
 
X 
 
 
 
 
 
Open-Label KP415 Dosing 12 
 
 
 
X 
X 
X 
X 
X 
Drug Accountability & Compliance 
Assessment 13 
 
 
 
 
X 
 
X 
 
ADHD-RS-5 14 
 
 
X 
 
X 
 
X 
 
MINI-KID 15 
X 
 
 
 
 
 
 
 
CGI-S 16 
X 
 
X 
 
X 
 
X 
 
CGI-I 17 
 
 
 
 
X 
 
X 
 
CSHQ 18 
 
 
X 
 
 
 
 
 
Adverse Events 19 
 
 
 
X 
X 
X 
X 
X 
Concomitant Medications 20 
X 
 
X 
 
X 
 
X 
 
BMI = Body Mass Index; ECG = Electrocardiogram; MPH = methylphenidate; see footnotes for other 
abbreviations. 
 
1. ADHD Diagnosis based on the Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) 


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criteria for a primary diagnosis of ADHD (combined, inattentive, or hyperactive/impulsive 
presentation) and confirmed by the Mini International Neuropsychiatric Interview for Children and 
Adolescents (MINI-KID). 
2. Capsule Swallowing Test: Subjects must be able to comply with one of the following:  
a) Subjects will take a size 3 capsule with up to 240 mL of water at Screening. The capsule may 
not contain any active drug substance. Subjects must be able to easily swallow the size 3 
capsule to be eligible for further study participation. This is not required for subjects who 
have previously participated in the KP415.E01 study.  
b) If subjects are unable to demonstrate that they can swallow size 3 capsules, they must agree 
to take the capsule contents sprinkled over a small amount of applesauce or added to a small 
amount of water during the study. 
Any of the methods of administration may be used on any day of the study, but if subjects plan to take 
study drug as the whole capsule, subjects will need to have demonstrated that they are able to 
swallow size 3 capsules at Screening or any time during the study (or have been previously 
participated in Study KP415.E01). 
3. Medical History: A complete medical history including chronic conditions, relevant surgical 
procedures (with start date), history of drug and alcohol use. As part of Medical History for Visit 1B 
(and with more details captured in the database), record treatment with study drug in Study KP415.E01 
with regards to dose, duration, date of last dose (Visit 6 in Study KP415.E01), last visit in Study 
KP415.E01 (Visit 7 in Study KP415.E01), etc. 
4. Height will be recorded in centimeters (cm) with the subject’s shoes removed. Body weight will be 
measured in kilograms (kg); subjects will remain in their normal clothing with shoes and jacket 
(and/or outer clothing) removed. 
5. Vital sign measurements will be obtained after the subject has been seated for at least 3 minutes. Vital 
signs will include sitting blood pressure (systolic and diastolic measurements), pulse rate (beats per 
minute), respiratory rate (breaths per minute), and oral temperature. Vital signs will be collected once 
at each visit. 
6. Electrocardiogram (ECG): A 12-lead ECG will be obtained after the subject has been in the supine 
position for at least 3 minutes. Abnormal ECGs may be repeated for confirmation in which case only 
the repeated ECG will be recorded. The QT interval corrected for heart rate will be calculated with 
Fridericia’s formula (QTcF). For roll-over subjects, if the Screening Visit (Visit 1B) occurs on the 
same day as the Follow-Up Visit (Visit 7) of Study KP415.E01, one ECG will be obtained to be used 
in both studies. If Visit 1B occurs later, after Visit 7 in E01, a new ECG will be obtained at Visit 1B 
as baseline for the current study. 
7. Urine Screen for Alcohol and Drugs of Abuse: Urine samples will be tested for alcohol, and drugs of 
abuse (amphetamines, methamphetamines, benzodiazepines, barbiturates, cannabinoids, cocaine, 
opioids including oxycodone) at Screening (Visit 1A or 1B). If the urine test is positive for any of the 
analytes at Screening, the subject will be excluded from study participation, with the exception of the 
following: Depending on a subject's current ADHD medication at Screening, the urine screen at 
Screening may test positive for ADHD medications such as amphetamines and methamphetamines. 
All ADHD medications must be washed out by Visit 2 for new subjects and Visit 5 for roll-over 
subjects. 
8. Urine Screen for Methylphenidate (MPH): For new subjects, urine samples will be tested for MPH at 
Screening (Visit 1A) and Visit 2. A urine dipstick (e.g., NarcoCheck®) will be used to screen for the 
presence of MPH in the urine. If a subject's current ADHD medication at Screening contains MPH, 
the urine screen at Screening (Visit 1A, new subjects) may test positive for MPH. All ADHD 
medications must be washed out by Visit 2 for new subjects and Visit 5 for roll-over subjects (MPH 
urine screen must test negative). 
9. Pregnancy Test: performed for female subjects of childbearing potential. A serum β-hCG pregnancy 
test will be performed at Screening. A urine pregnancy test will be performed at Visit 2. A positive 
pregnancy test at Screening or before the last dose of study drug will exclude a subject from further 


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participation in the study. 
10. Columbia Suicide Severity Rating Scale (C-SSRS): The “Children’s Baseline/Screening” version will 
be assessed at Screening, and the “Children’s Since Last Visit” version will be assessed at all other 
visits. Subjects who have, in the opinion of the Investigator, clinically significant suicidal 
ideation/behavior, based on history of attempted suicide and the C-SSRS assessment at Screening or 
at any time before the last dose of study drug, will be excluded from further participation in the study. 
11. All Subjects must wash out ADHD medications prior to Visit 2. Stimulant ADHD medications (with 
the exception of study drug), including herbal medications, are prohibited from 5 days prior to Visit 2 
for new subjects and prior to Visit 5 for rolled-over subjects to the end of the Follow-Up Visit or 
Early Termination Visit. Before or on the day during the screening period that subjects will need to 
start the washout of their ADHD medications (for example, 5 days before Visit 2 for stimulants), 
study site staff will contact the subject’s parent/guardian by phone to remind them of the washout 
(“washout phone call”). 
 
Non-Stimulant ADHD medications are prohibited from 14 days prior to the start of the Dose 
Optimization Phase (Visit 2) to the end of the Follow-Up Visit or Early Termination Visit. Other 
prohibited medications with their associated time windows when they are prohibited are listed in the 
protocol. 
12. KP415 Dose Optimization: Subjects will begin taking open-label KP415 at home the morning 
following Visit 2. The starting dose of KP415 (Days 1-7 ±3 days) will be 30 mg/day. KP415 dose 
adjustments, if needed, will be performed at approximately weekly intervals between visits (at Visits 
3 and 4). Actual visit dates may deviate from exactly being spaced 7 days apart such that the total 
duration of the Dose Optimization Phase is 3 weeks (21 days) ±3 days. The daily doses of KP415 
used in the Dose Optimization Phase will be 20, 30, and 40 mg (dose optimization range of ≥20 and 
≤40 mg). At Visits 3 and 4, based on the CGI scores, interview with the parent/guardian/caregiver, 
and safety data, the Investigator will evaluate the subject’s therapeutic responses and tolerability to 
treatment and decide whether the current KP415 dose should be increased, decreased, or remain the 
same for the next week of dosing. If subjects experience symptoms of intolerance during the at-home 
treatment, they must contact the clinical site, and, at the discretion of the Investigator, their KP415 
dose may be adjusted before the next scheduled visit. Unscheduled visits between Visits 2, 3, and 4 
are allowed as needed, at the discretion of the Investigator. 
13. Drug Accountability & Compliance Assessment: All study drug will be recorded by each site’s 
pharmacy staff member or Investigator-delegated employee. A record of the study drug accountability 
will be prepared and kept by the clinical site. 
14. ADHD-Rating Scale-5 (ADHD-RS-5) assessment: 1 assessment at the indicated visits. 
15. Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID): For 
confirmation of ADHD diagnosis at Screening. 
16. Clinical Global Impressions–Severity (CGI-S) scale assessment: 1 assessment at the indicated visits. 
17. Clinical Global Impressions–Improvement (CGI-I) scale assessment: 1 assessment at the indicated 
visits. 
18. Children’s Sleep Habits Questionnaire (CSHQ) assessment: 1 assessment at Visit 2. 
19. Adverse Events: To be assessed and recorded in the eCRF following the first dose of open-label drug 
(KP415), on Day 1, through either Follow-Up or Early Termination. Subject’s parent/guardian will be 
instructed to contact the study site for the reporting of AEs during the dosing periods at home. 
20. Concomitant Medications: new and/or changed medications and dose, medical treatments and/or 
therapies will be recorded at Screening through either Follow-Up or Early Termination. 
21. Actual visit dates in the Dose Optimization Phase may deviate from exactly being spaced 7 days apart 
such that the total duration of the Dose Optimization Phase ranges between 18 and 24 days (21 ±3 
days). Any allowed deviation (up to 3 days in total) of the targeted 21-day Dose Optimization Phase 
will be carried over into the actual days for the subsequent visits. 
22. Subjects who meet withdrawal criteria post-dose during the Dose Optimization Phase (after at least 
one dose of study drug is administered) will complete Early Termination procedures as listed in the 


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Schedule of Events in Section 1.3. This includes subjects who do not meet the eligibility criteria to 
continue in the Treatment Phase. At the discretion of the Investigator, ensuring the safety of the 
subjects, any Early Termination procedures that were already performed on the same day as part of 
the procedures of the Dose Optimization Phase, do not need to be repeated. Subjects who withdraw 
early from the study and complete the ET procedures will not return for a Follow-Up Visit. Therefore, 
the ET Visit is the End-of-Study (EOS) for these subjects. 
23. The procedures at Screening are different between subjects rolled over from Study KP415.E01 and 
new subjects. Therefore, the Screening Visit for roll-over subjects is designated as Visit 1B, and for 
new subjects is designated Visit 1A. Visits 2, 3 and 4 are not needed for subjects rolled over from 
Study KP415.E01 because their optimum dose was determined in the Dose Optimization Phase of 
Study KP415.E01. Therefore, rolled-over subjects from Study KP415.E01 will start with Visit 1B as 
the first visit of the current study, followed by Visit 5 as the next visit (rolled-over subjects will not 
have Visits 2, 3 and 4). 
24. The Screening Visit for rolled-over subjects (Visit 1B) may occur on the same day as the EOS (Visit 
7, Follow-Up) in Study KP415.E01 or later, and must occur within 30 days before Visit 5 in the 
current study. For roll-over subjects, the Investigator has the option to use the clinical laboratory 
(clinical chemistry, hematology and urinalysis) results from the Follow-Up Visit in Study KP415.E01 
(Visit 7) in lieu of collecting new blood samples at Screening (Visit 1B) in the current study, as long 
as the clinical laboratory samples from the E01 study were collected within 30 days prior to 
Screening (Visit 1B) in the current study. For all roll-over subjects who are children of childbearing 
potential, a blood sample for the measurement of a serum pregnancy test is needed at Visit 1B. For 
other assessments required at Visit 1B (C-SSRS, for example), the Visit 7 assessments from the E01 
study (if collected) can be used as long as Visit 1B is conducted on the same day as Visit 7 in the E01 
study. Visit 7 clinical laboratory samples collected during KP415.E01 (also used as the Visit 1B 
results) are not required to be collected under fasting conditions. During Visit 1B of the current study, 
the study site will document whether these samples were collected under fasting/non-fasting 
conditions, and this will be recorded in the database. 
 


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1.2. Treatment Phase (First 6 Months; All Subjects) 
ASSESSMENTS 
OPEN-LABEL 
TREATMENT PHASE 19 
Study Day  
0 
1-29 
(±5 
days) 
30 
(±5 
days) 
31-59 
(±5 
days) 
60 
(±5 
days) 
61-89 
(±5 
days) 
90 
(±5 
days) 
91-
119 
(±5 
days) 
120 
(±5 
days) 
121-
149 
(±5 
days) 
150 
(±5 
days) 
151-
179 
(±5 
days) 
180 
(±5 
days) 
Visit Number 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
11 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 2 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Body Weight, Height, BMI 3 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Vital Signs 4 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
12-Lead ECG 5 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Chemistry/Hematology/Urinalysis 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Urine MPH Screen (roll-overs) 6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 7 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
C-SSRS 8 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Prohibited Medications 9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Eligibility Criteria (new subjects) 10 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment in Treatment Phase 11 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Open-Label KP415 Dosing 12 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Drug Accountability & Compliance 
Assessment 
X 22 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
ADHD-RS-5 13 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
CGI-S 14 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
CGI-I 15 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CSHQ 16 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Adverse Events 17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 18 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Interim Analysis 23 
 
 
 
 
 
 
 
 
 
 
 
 
X 
EOS = End of Study; ET = Early Termination; BMI = Body Mass Index; ECG = Electrocardiogram; see footnotes for other abbreviations. See 


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Section 1.3 for all footnotes. 
 


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1.3. Treatment Phase (Second 6 Months), and Early Termination and Follow-Up Visits (All Subjects) 
ASSESSMENTS 
OPEN-LABEL 
TREATMENT PHASE 19 
ET 21 
(EOS) 
FOLLOW-UP 
(EOS) 
Study Day 
181-
209 
(±5 
days) 
210 
 
(±5 
days) 
211-
239 
(±5 
days) 
240 
 
(±5 
days) 
241-
269 
(±5 
days) 
270 
 
(±5 
days) 
271-
299 
(±5 
days) 
300 
 
(±5 
days) 
301-
229 
(±5 
days) 
330 
 
(±5 
days) 
331-
359 
(±5 
days) 
360 20 
 
(±5 
days) 
- 
343-383 
 
(±2 days) 
19 
Visit Number 
 
12 
 
13 
 
14 
 
15 
 
16 
 
17 
- 
18 
Physical Examination 2 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Body Weight, Height, BMI 3 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Vital Signs 4 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
12-Lead ECG 5 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Chemistry/Hematology/Urinalysis 
(under fasting conditions) 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Pregnancy Test 7 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
C-SSRS 8 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Prohibited Medications 9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Open-Label KP415 Dosing 12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Drug Accountability & Compliance 
Assessment 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
ADHD-RS-5 13 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
CGI-S 14 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
CGI-I 15 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CSHQ 16 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Adverse Events 17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 18 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
EOS = End of Study; ET = Early Termination; BMI = Body Mass Index; ECG = Electrocardiogram; see footnotes for other abbreviations. 
 
 


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1. Medical History: A complete medical history including chronic conditions, relevant surgical procedures (with start date), history of drug and 
alcohol use. 
2. Physical examination at Visit 11, and at Visit 17 (EOT) or at Early Termination (if possible). 
3. Body weight, height and BMI at each visit. Height will be recorded in centimeters (cm) with the subject’s shoes removed. Body weight will be 
measured in kilograms (kg); subjects will remain in their normal clothing with shoes and jacket (and/or outer clothing) removed. 
4. Vital sign measurements will be obtained after the subject has been seated for at least 3 minutes. Vital signs will include sitting blood pressure 
(systolic and diastolic measurements), pulse rate (beats per minute), respiratory rate (breaths per minute), and oral temperature. Vital signs will 
be collected once at each visit. 
5. Electrocardiogram (ECG): A 12-lead ECG will be obtained after the subject has been in the supine position for at least 3 minutes. Abnormal 
ECGs may be repeated for confirmation in which case only the repeated ECG will be recorded. The QT interval corrected for heart rate will be 
calculated with Fridericia’s formula (QTcF). 
6. Urine Screen for Methylphenidate (MPH): Urine samples will be tested for MPH at Visit 5 for roll-over subjects. A urine dipstick (e.g., 
NarcoCheck®) will be used to screen for the presence of MPH in the urine. All ADHD medications must be washed out by Visit 5 for roll-over 
subjects. Subjects with a positive MPH urine screen at Visit 5 will be excluded from further participation in the study or may be retested at a 
later date, and may be enrolled if the MPH urine screen retest is negative as long as the Screening Window is adhered to. 
7. A urine pregnancy test will be performed for female subjects of childbearing potential at all visits during the Treatment Phase, and at Early 
Termination or Follow-Up. A positive pregnancy test before the last dose of study drug will exclude a subject from further participation in the 
study. 
8. Columbia Suicide Severity Rating Scale (C-SSRS): The “Children’s Since Last Visit” version will be assessed at all visits the Treatment Phase, 
and at Early Termination or Follow-Up. Subjects who have, in the opinion of the Investigator, clinically significant suicidal ideation/behavior, 
based on history of attempted suicide and the C-SSRS assessment at Screening or at any time before the last dose of study drug, will be 
excluded from further participation in the study. 
9. Stimulant ADHD medications (with the exception of study drug), including herbal medications, are prohibited from 5 days prior to Visit 5 to the 
end of the Follow-Up Visit or Early Termination Visit. 
Non-Stimulant ADHD medications are prohibited from 14 days prior to the start of Visit 5 to the end of the Follow-Up Visit or Early 
Termination Visit. Other prohibited medications with their associated time windows when they are prohibited are listed in the protocol body 
text. 
10. At Visit 5, for new patients, the Investigator will evaluate the eligibility criteria based on assessments in the Dose Optimization Phase, for 
continuation into the subsequent Treatment Phase. For subjects eligible for the Treatment Phase, the optimal daily KP415 dose will be used as 
the daily KP415 dose in the Treatment Phase. This is not needed for subjects rolled over from Study KP415.E01 because their optimum dose 
was determined in the Dose Optimization Phase of Study KP415.E01. Rolled-over subjects from Study KP415.E01 will start with Visit 1B as 
the first visit of the current study, followed by Visit 5 as the next visit (rolled-over subjects will not have Visits 2, 3, and 4). 
11. Enrollment in the Treatment Phase: Subjects able to tolerate at least 20 mg/day of KP415 and with an adequate dose-response will be enrolled 
into the Treatment Phase. The determination of tolerability and adequate dose-response will be determined in Study KP415.E01 for subjects 
rolled over from Study KP415.E01 (they will need to have completed Study KP415.E01), or at the end of the Dose Optimization Phase in the 
current study for new subjects. Subjects rolled over from Study KP415.E01 will be enrolled in the Treatment Phase of the current study (Visit 5) 


Protocol KP415.S01 Amendment #3 
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within 45 days after the last dose of study drug in Study KP415.E01 (Visit 6 in Study KP415.E01). New subjects will continue to the Treatment 
Phase immediately after the end of the Dose Optimization Phase in the current study. Subjects not rolled over from Study KP415.E01 within 45 
days of the last dose of study drug, may be enrolled in the current study as new subjects (they will need to start with Screening and Dose 
Optimization Phase). At the start of the Treatment Phase (Visit 5), the appropriate open-label study drug to be taken at home once-a-day in the 
morning on each of the days of the Treatment Phase until the next visit will be dispensed to the subjects. 
12. Study Drug Administration: All subjects eligible to participate in the Treatment Phase will receive non-blinded oral capsules with active KP415 
drug (one capsule). The dose level is an optimized KP415 dose of 20, 30, or 40 mg determined at the end of the Dose Optimization Phase in 
Study KP415.E01 for rolled-over subjects from Study KP415.E01, or as determined at the end of the Dose Optimization Phase in the current 
study for new subjects. 
Based on individual tolerability and dose-response during the Treatment Phase, at the discretion of the Investigator, the KP415 dose may be 
changed (increased or decreased, but one of the 3 dose levels of 20, 30, or 40 mg KP415 capsules). All study drugs will be given orally. Subjects 
will take study drug (one capsule/day) in the morning at home under supervision of their parent or legal guardian. The final dose of study drug 
will be administered on the last day of the Treatment Phase (Day 360 ±20 days; Visit 17). If the study is stopped earlier based on the stopping 
rules, the last day of the Treatment Phase (Visit 17) may occur earlier than Day 360 for some or all subjects. Study drug will be taken orally 
with up to 210-240 mL of water. The capsule needs to be swallowed whole (without crushing, cutting, crushing, chewing, opening, or 
dissolving) or may be taken by sprinkling the contents of the capsule over a small amount of applesauce, or putting the contents in a small 
amount of water. 
13. ADHD-Rating Scale-5 (ADHD-RS-5) assessment: 1 assessment at the indicated visits. 
14. Clinical Global Impressions–Severity (CGI-S) scale assessment: 1 assessment at the indicated visits. 
15. Clinical Global Impressions–Improvement (CGI-I) scale assessment: 1 assessment at Visit 5 for new subjects only. 
16. Children’s Sleep Habits Questionnaire (CSHQ) assessment: 1 assessment at the indicated visits. 
17. Adverse Events: To be assessed and recorded in the eCRF following the first dose of open-label drug (KP415), through either Early Termination 
or Follow-Up. Subject’s parent/guardian will be instructed to contact the study site for the reporting of AEs while away from the study site. 
18. Concomitant Medications: new and/or changed medications and dose, medical treatments and/or therapies will be recorded at Visit 5 through 
either Follow-Up or Early Termination. 
19. To allow flexibility in scheduling visits, actual visit dates for individual subjects in the Treatment Phase may deviate from exactly being spaced 
30 days apart (up to 30 ±5 days from the previous visit) such that the total duration of the Treatment Phase may be in the range of 360 ±20 days 
(340-380 days from Visit 5 to Visit 17). The Follow-Up Visit (3 days after the last dose) therefore falls between Day 343 and Day 383, but has 
its own window of ±2 days added. 
20. The end of the Treatment Phase is on Day 360 ±20 days (Visit 17), after all post-dosing procedures are completed. 
21. Subjects who meet withdrawal criteria post-dose during the Treatment Phase (after at least one dose of study drug is administered) will complete 
Early Termination procedures. At the discretion of the Investigator, ensuring the safety of the subjects, any Early Termination procedures that 
were already performed on the same day as part of the procedures of the Treatment Phase, do not need to be repeated. Subjects who withdraw 
early from the study and complete the ET procedures will not return for a Follow-Up Visit. Therefore, the ET Visit is the End-of-Study (EOS) 
for these subjects. 
22. Drug Accountability & Compliance Assessment: All study drug will be recorded by each site’s pharmacy staff member or Investigator-


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delegated employee. A record of the study drug accountability will be prepared and kept by the clinical site at each visit for subjects receiving 
study drug since the previous visit (including drug accountability at Visit 5 for drug returned from the last week of the Dose Optimization Phase, 
by new subjects). 
23. An interim analysis of the safety data will be conducted after approximately all subjects remaining in the study have completed 180 days 
(approximately 6 months) of treatment. After the completion of the interim analysis, based on the acceptance of the clinical and nonclinical 
safety database from the current study and other studies, the Sponsor may stop the study. Treatment in the current study will continue as planned 
while the interim analysis is conducted. If the decision is made to stop the study, all subjects remaining in the study will undergo the EOT Visit 
(with safety evaluations including fasting safety labs and ECGs) and a Follow Up Visit. 


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2. BACKGROUND 
2.1. Attention-Deficit Hyperactivity Disorder (ADHD) 
ADHD is a common neurobehavioral disorder that occurs in 6-8% of children and 4-5% of adults 
worldwide (Wilens 2008). The 3 main symptoms of ADHD include inattention, hyperactivity, and 
impulsivity. ADHD is theorized to result from a deficiency of neurotransmission of dopamine and 
norepinephrine either through the insufficient sensitivity of the receptors or amount of dopamine 
produced. The most common and effective therapeutics for the treatment of ADHD are CNS 
stimulants, which contain amphetamine or methylphenidate (MPH). Amphetamine-containing 
products include brand names such as Adderall®, Dexedrine®, Dextrostat®, and Vyvanse®. 
Methylphenidate containing products include Metadate®, Concerta®, Daytrana®, Ritalin®, 
Methylin®, Quilivant®, and Focalin®. Positive effects on behavior and academic productivity are 
well established for stimulant medications such as MPH (Wilens and Biederman 1992). Several 
studies have shown that, in children with ADHD, MPH improves classroom functioning, notably 
by decreasing disruptive behavior and increasing academic productivity, accuracy and 
improvement in teacher ratings. In addition, MPH has been shown to improve performance in 
children for several cognitive tasks, including measures of attention and memory. 
2.2. KP415: A Prodrug Conjugate of d-Methylphenidate 
KemPharm is developing KP415 as an extended release (ER) prodrug of d-threo-MPH HCl. 
Chemically, KP415 consists of a single d-threo-MPH molecule covalently attached via a carbamate 
bond to a methylene oxide linker which in turn is connected to the nitrogen of the pyridine ring of 
a nicotinoyl-serine moiety. The covalent linkage makes KP415 a new chemical entity (NCE). 
Results from preliminary in vivo studies in rats have shown that the prodrug has unique 
pharmacokinetic (PK) properties that suggest it will have reduced intranasal and intravenous abuse 
potential. 
As a prodrug, KP415 represents a potential abuse-deterrent form of MPH with abuse-deterrent 
properties that are imparted at the molecular level. Some of the KP415 attributes that make it worthy 
of further development are highlighted below: 
• KP415 has negligible pharmacological activity at key receptors that are responsible for the 
efficacy of d-MPH for the treatment of ADHD. 
• When administered intranasally or intravenously in rats, KP415 resulted in d-MPH plasma 
concentrations that are significantly reduced when compared to d-MPH HCl. 
• KP415 exhibits chemical stability when subjected to certain hydrolytic conditions with the 
intention to extract methylphenidate. 


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3. OVERVIEW OF CLINICAL STUDIES WITH KP415 
The pharmacology, metabolism and toxicology of methylphenidate are well established (Challman 
and Lipsky 2000, Leonard 2004). Methylphenidate is a CNS stimulant approved for the treatment 
of ADHD and narcolepsy. Methylphenidate inhibits the reuptake of dopamine and norepinephrine, 
increased dopaminergic and noradrenergic activity in the prefrontal cortex may explain its efficacy 
in ADHD. 
Common side effects of methylphenidate include nervousness, agitation, anxiety, sleep problems 
(insomnia), stomach pain, decreased appetite, weight loss, nausea, vomiting, dizziness, palpitations, 
headache, vision problems, increased heart rate, increased blood pressure, sweating, skin rash, 
psychosis, and numbness, tingling, or cold feeling in hands or feet. When abused, methylphenidate 
produces toxicity similar to other CNS stimulant overdoses (Morton and Stockton 2000). Supra-
therapeutic doses have shown to cause delirium, hallucinations, bruxism (jaw-grinding), and 
trismus (jaw clenching) (Morton and Stockton 2000). 
3.1. Study KP415.101 
This Phase 1 proof-of-concept trial (Study KP415.101) was designed to assess the PK of 32 mg of 
KP415 API (liquid, dissolved in water) compared with 36 mg of Concerta® (tablet) after oral 
administration under fasted conditions. Twenty-four (24) healthy adult volunteers were enrolled in 
this open-label, single-dose, two-treatment, two-period PK trial. Dosing levels in each treatment 
were not molar equivalent amounts of d-MPH: 36 mg Concerta® contained approximately 12% 
more d-MPH than 32 mg of the KP415 prodrug API (standalone KP415). 
KP415 API prodrug effectively released the active d-MPH into the bloodstream which is consistent 
with previously collected preclinical data. After KP415 API prodrug dosing, the mean peak 
concentration (Cmax) of d-MPH was 2.9 ng/mL at a median Tmax of 8 hr compared to 8.0 ng/mL at 
6 hr after Concerta®. 
The mean systemic exposure (AUC0-last) for d-MPH was 44 ng•hr/mL after KP415 API prodrug 
versus 97 ng•hr/mL after Concerta® dosing. The mean total systemic exposure (AUC0-inf) for d-
MPH was 100 ng•hr/mL after KP415 API prodrug versus 102 ng•hr/mL after Concerta® dosing. 
The mean terminal elimination plasma half-life (T1/2) of d-MPH was 25 hr after KP415 API prodrug 
versus 4 hr after Concerta®. 
After oral dosing of standalone KP415, it appears that that there is rapid absorption of prodrug 
followed by slow release of d-MPH resulting in a gradual onset followed by a slow extended release 
of d-MPH. The later Tmax and longer T1/2 for d-MPH after KP415 dosing indicate that KP415 as a 
prodrug of d-MPH has extended-release (ER) properties that support a once-per-day dosing 
schedule for an ADHD indication. The ER properties inherent in the KP415 prodrug molecule can 
subsequently provide sustained d-MPH exposure, as desired for a once-per-day treatment of ADHD 


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in adults. No l-MPH levels were detected after KP415 dosing and very low l-MPH levels were 
measured after Concerta® dosing. 
Both treatments were generally well-tolerated. There were no apparent changes in vital signs and 
ECG parameters between treatments. Safety laboratory values were approximately the same after 
the treatment phase versus those measured at Screening. 
3.2. Study KP415.109 
This Phase 1 open-label PK study included a treatment group wherein healthy adult volunteers were 
dosed for 7 days with oral daily doses of 12 mg d-MPH API (immediate release component) and 
56 mg KP415 prodrug API, each administered as an oral liquid in water immediately after each 
other. The total daily equivalent d-MPH dose was 40 mg. This dose was the same as the highest 
dose that will be used in the current protocol. 
The mean d-MPH plasma concentrations on Day 7 of Study KP415.109 are presented in Figure 1. 
The mean d-MPH trough concentration (Cmin; pre-dose on Day 7) was 3.3 ng/mL and the mean d-
MPH peak concentration (Cmax on Day 7) was 20.9 ng/mL at a median Tmax of 1.5 hr. The mean 
systemic exposure over the dosing interval (AUC0-24hr) for d-MPH was 208 ng•hr/mL and the mean 
terminal elimination plasma half-life (T1/2) of d-MPH was 8.9 hr. The mean accumulation ratios 
(Day 7/Day 1 ratios) for Cmin, Cmax and AUC0-24hr were 1.31, 1.20 and 1.34, respectively. The 
combination of 70%/30% KP415/d-MPH resulted in early peak d-MPH exposure followed by 
sustained d-MPH exposure, as desired for chronic, once-per-day treatment of ADHD in a pediatric 
population. The efficacy and safety of this combination in children 6-12 years old with ADHD will 
be studied in the study presented in this protocol. 


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Figure 1: Mean (N=10) d-Methylphenidate (d-MPH) Concentrations after the 7th Oral Daily 
Dose of 12 mg d-MPH and 56 mg KP415 Prodrug (Together Equivalent to 40 mg d-MPH) 
 
4. STUDY RATIONALE 
The safety of KP415 has been investigated in pharmacokinetic studies with healthy adult volunteers 
after daily oral doses of up to 7 days. In addition, the efficacy and safety in children 6-12 years old 
with ADHD is being investigated in Study KP415.E01. Study KP415.E01 is a multicenter, dose-
optimized, double-blind, randomized, placebo-controlled, parallel efficacy laboratory classroom 
study with KP415 with daily oral KP415 administration up to 4 weeks. The rationale of the current 
study is to investigate the safety and tolerability of daily oral KP415 doses for a longer duration. In 
addition, the current study will also determine the efficacy and sleep behavior of KP415 in treating 
children with ADHD. For ease of enrollment and to extend the duration of dosing already available 
from Study KP415.E01, the study population will include subjects rolled over from Study 
KP415.E01 (A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled, 
Parallel Efficacy Laboratory Classroom Study with KP415 in Children with Attention-
Deficit/Hyperactivity Disorder). 
5. STUDY OBJECTIVES 
5.1. Primary Objective 
To determine the safety and tolerability of KP415 in treating children with ADHD. 


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5.2. Secondary Objectives 
To determine the efficacy and changes in sleep behavior during KP415 treatment in children with 
ADHD. 
6. INVESTIGATIONAL PLAN 
6.1. Study Design 
The study is a multicenter, multiple-dose, dose-optimized, open-label safety study with KP415 
administered orally in children with Attention-Deficit/Hyperactivity Disorder (ADHD). 
Approximately 20 sites in the United States of America will take part in the study. 
6.1.1. Definition of “Rolled-Over Subjects” or “New Subjects” 
Eligible subjects for the current study will be either “Rolled-Over Subjects” or “New Subjects”, 
defined as follows: 
• Rolled-Over Subjects are those who successfully completed Study KP415.E01 and rolled 
over (i.e., received first dose in the current study) within 45 days of the last dose of study 
drug in Study KP415.E01. The roll-over window (for Rolled-Over Subjects), dose-to-dose 
between both studies (i.e., gap between the last dose in Study KP415.E01 [Visit 6] and the 
first dose in the current study [Visit 5]) is maximum 45 days. For roll-over subjects, the 
Investigator has the option to use the clinical chemistry and hematology results from the 
Follow-Up Visit in Study KP415.E01 (Visit 7) in lieu of collecting new blood samples at 
Screening (Visit 1B) in the current study, as long as the clinical chemistry and hematology 
data from the E01 study were collected within 30 days of Screening (Visit 1B) in the current 
study. For all roll-over subjects who are children of childbearing potential, a blood sample 
for the measurement of a serum pregnancy test is needed at Visit 1B. For other assessments 
required at Visit 1B (C-SSRS, for example), the Visit 7 assessments from the E01 study (if 
collected) can be used as long as Visit 1B is conducted on the same day as Visit 7 in the E01 
study. 
• New Subjects are those who did not participate in Study KP415.E01 or completed the last 
dose in Study KP415.E01 more than 45 days before the first dose in the current study. 
Subjects who completed other studies with KP415 (for example, the single-dose 
pharmacokinetic study KP415.105) may be enrolled in the current study as new subjects 
after a minimum 5-day washout period between the last dose of KP415 and Screening in the 
current study. 
Rolled-over subjects and new subjects will need to meet their respective inclusion/exclusion criteria 
listed in Section 7.2. 


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6.1.2. Study Participation 
The study visits, treatment and procedures leading up to the Treatment Phase are different for rolled-
over and new subjects, as follows: 
• Rolled-Over Subjects: For subjects rolled over from Study KP415.E01, the study will 
consist of a Screening Phase, Treatment Phase and a Follow-Up Visit. These subjects will 
be enrolled in the Treatment Phase of the current study (first dose at Visit 5) within 45 days 
after the last dose of study drug in Study KP415.E01. The roll-over window (for Rolled 
Over Subjects), dose-to-dose between both studies (i.e., gap between the last dose in Study 
KP415.E01 [Visit 6] and the first dose in the current study [Visit 5]) is maximum 45 days. 
Subjects are allowed to enter Screening (Visit 1B) on the same day as the Follow-Up Visit 
in Study KP415.E01, or later. Subjects not rolled over from Study KP415.E01 within 45 
days of the last dose of study drug, may be enrolled in the current study as new subjects 
(they will need to start with Screening followed the by Dose Optimization Phase – see New 
Subjects below). These subjects will be considered New Subjects and will undergo all the 
visits and procedures of New Subjects (starting with Visit 1A as the Screening Visit). For 
roll-over subjects, the Investigator has the option to use the clinical chemistry and 
hematology results from the Follow-Up Visit in Study KP415.E01 (Visit 7) in lieu of 
collecting new blood samples at Screening (Visit 1B) in the current study, as long as the 
clinical chemistry and hematology data from the E01 study were collected within 30 days 
of Screening (Visit 1B) in the current study. For all roll-over subjects who are female 
subjects of childbearing potential, a blood sample for the measurement of a serum pregnancy 
test is needed at Visit 1B. For other assessments required at Visit 1B (C-SSRS, for example), 
the Visit 7 assessments from the E01 study (if collected) can be used as long as Visit 1B is 
conducted on the same day as Visit 7 in the E01 study. 
• New Subjects: For new subjects, the study will consist of a Screening Period, a Dose 
Optimization Phase, a Treatment Phase and a Follow-Up Visit.  
The study design and procedures in the Treatment Phase, the Follow-Up Visit and the Early 
Termination Visit are the same for new subjects and rolled-over subjects. 
6.1.3. Study Phases and Treatment 
All subjects will receive unblinded (open-label) active drug (KP415 capsules) in all phases of 
the study wherein study drug is administered. 
The phases of the study are as follows: 
• Screening Period: New Subjects will undergo a screening period up to 30 days prior to 
entering into the Dose Optimization Phase. Rolled-over subjects will undergo a screening 


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period up to 30 days prior to entering into the Treatment Phase. 
• Dose Optimization Phase (for new subjects only): During the Dose Optimization Phase, 
subjects will be titrated to doses of 20, 30 or 40 mg KP415 capsules based on individual 
tolerability and best dose-response in the opinion of the Investigator. 
• Treatment Phase: Eligible subjects will receive single daily oral doses of KP415 for 
approximately 360 days (approximately 12 months), or for a shorter duration if the study is 
stopped earlier (see Section 8.6 for the study stopping rules). The starting dose of KP415 
given in the Treatment Phase will be the same as the optimized dose of KP415 determined 
and used in Study KP415.E01 for rolled-over subjects, or determined at the end of the Dose 
Optimization Phase for new subjects. During the Treatment Phase, the dose of KP415 may 
be changed based on individual tolerability and best dose-response (to either 20, 30 or 40 
mg KP415 capsules). Safety, efficacy and sleep behavior assessments will be performed. 
• Follow-Up Visit: 3 ±2 days after administration of the last dose of the Treatment Phase, 
subjects will enter a Follow-Up Visit to evaluate safety parameters. 
6.2. Study Duration 
Rolled-Over Subjects: Subjects rolled over from Study KP415.E01 will participate in the study as 
outpatients for up to 416 days, including up to 30 days of Screening, 1 day for Visit 5, up to 380 
days (360 ±20 days) in the Treatment Phase and a Follow-Up Visit up to 5 days (3 ±2 days) after 
the administration of the last dose of the Treatment Phase. Subjects who completed Study 
KP415.E01 and start the current study outside the 45-day roll-over window will be considered new 
subjects and will undergo all the visits and procedures of new subjects. 
New Subjects: New subjects will participate in the study as outpatients for up to 440 days including 
up to 30 days of Screening, 1 day for Visit 2, up to 23 days (20 ±3 days) in the Dose Optimization 
Phase, 1 day for Visit 5, up to 380 days (360 ±20 days) in the Treatment Phase and a Follow-Up 
Visit up to 5 days (3 ±2 days) after the administration of the last dose of the Treatment Phase. 
If the study is stopped earlier based on the study stopping rules (see Section 8.6), all or some 
subjects may participate in the study for shorter durations than those listed above. 
7. SUBJECT SELECTION 
7.1. Number of Subjects 
Approximately 250 subjects will be enrolled in the Treatment Phase of the study. Subjects will be 
rolled over from Study KP415.E01 and to reach the targeted number of subjects, new subjects will 
be enrolled as well. Subjects who fail Screening and new subjects who terminate early during the 
Dose Optimization Phase may be replaced. Subjects who terminate early in the Treatment Phase 


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will not be replaced. 
7.2. Study Population 
Subjects rolled over from Study KP415.E01 or new subjects with ADHD who meet the 
inclusion/exclusion criteria listed below. See Section 6.1.1 for the definitions of rolled-over subjects 
and new subjects. 
7.2.1. Inclusion Criteria for Subjects Rolled Over from Study KP415.E01 
(To be evaluated at Screening Visit 1B, except when noted otherwise) 
A subject will be eligible for inclusion in the study if all the following criteria apply: 
 
1. Subjects must have completed the Double-Blind Treatment Phase of Study KP415.E01, and 
must have received the last dose of KP415 in Study KP415.E01 (Visit 6) within 45 days 
prior to the first dose in the current study (Visit 5). Subjects who completed Study 
KP415.E01 but received their last dose of study drug more than 45 days prior to Visit 5 are 
eligible in the current study as New Subjects (but not as rolled-over subjects). Subjects who 
completed Study KP415.E01 and start the current study outside the 45-day roll-over window 
will be considered New Subjects and will undergo all the visits and procedures of new 
subjects (starting with Visit 1A as the Screening Visit). 
2. Subjects rolled-over from Study KP415.E01 needed to be at least 6 years old and less than 
13 years old at the start of the Dose Optimization Phase in Study KP415.E01. By the time 
they are rolled over into the current study, some may be 13 years old. 
3. Female subjects must agree, when they are of childbearing potential at Screening or when 
they become of childbearing potential during the study, to remain abstinent or agree to use 
an effective and medically acceptable form of birth control from the time of written or verbal 
assent to at least 14 days after the last dose of study drug has been taken. Male subjects with 
female partners must agree, when their partners are of childbearing potential at Screening 
or when their partners become of childbearing potential during the study, to remain abstinent 
or agree to use an effective and medically acceptable form of birth control from the time of 
written or verbal assent to at least 14 days after the last dose of study drug has been taken. 
“Of childbearing potential” is defined in Section 12.9. Acceptable forms of birth control are 
listed in Section 10.3. 
4. Subject must be in general good health defined as the absence of any clinically relevant 
abnormalities as determined by the Investigator based on physical and neurological 
examinations, vital signs, ECGs, medical history, and clinical laboratory values 
(hematology, chemistry, and urinalysis) at the Follow-Up Visit of Study KP415.E01. If any 
of the hematology, chemistry, or urinalysis results are not within the laboratory's reference 


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range, then the subject can be included only if the Investigator determines the deviations to 
be not clinically relevant. 
5. At least one parent/legal guardian of the subject must voluntary give written permission for 
him/her to participate in the study. 
6. Subject must give written or verbal assent prior to study participation. For verbal assent, the 
procedure will be documented and signed by a witness. A parent or guardian may not be the 
witness for a child's verbal assent document. 
7. Subject must be able and willing to wash out current stimulant ADHD medications (if 
applicable, if taking ADHD medications between studies), including herbal medications 
from 5 days prior to the start of the Treatment Phase (Visit 5), and abstain from taking these 
to the end of the Follow-Up Visit or Early Termination; and wash out non-stimulant ADHD 
medications (if applicable) from 14 days prior to the start of the Treatment Phase (Visit 5), 
and abstain from taking these to the end of the Follow-Up Visit or Early Termination. 
8. Subject, subject’s parent/legal guardian and caregiver (if applicable) must understand and 
be willing and able to comply with all study procedures and visit schedule. If the subject is 
cared for by a caregiver for relevant parts of any period between study visits, and if in this 
case, in the opinion of the Investigator, the caregiver of the subject is more suitable for 
certain assessments, the caregiver will need to agree to the applicable procedures and visits. 
9. Subject, parent/legal guardian and caregiver (if applicable) must be able to speak and 
understand English, and be able to communicate satisfactorily with the Investigator and 
study coordinator. 
10. Subject must be able to swallow size 3 capsules as demonstrated by easily swallowing a size 
3 placebo capsule at Screening, unless the subject participated in the KP415.E01 study 
previously, or unless the subjects agrees to take the contents of the capsule sprinkled on a 
small amount of applesauce or in a small amount of water. 
7.2.2. Inclusion Criteria for New Subjects 
(To be evaluated at Screening Visit 1A, except when noted otherwise) 
A subject will be eligible for inclusion in the study if all the following criteria apply: 
1. Subject must be at least 6 years old and less than 13 years old at the start of the Dose 
Optimization Phase (Visit 2). 
2. Subject must have a body weight of at least 21 kg at Screening. 


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3. Female subjects must agree, when they are of childbearing potential at Screening or when 
they become of childbearing potential during the study, to remain abstinent or agree to use 
an effective and medically acceptable form of birth control from the time of written or verbal 
assent to at least 14 days after the last dose of study drug has been taken. Male subjects with 
female partners must agree, when their partners are of childbearing potential at Screening 
or when their partners become of childbearing potential during the study, to remain abstinent 
or agree to use an effective and medically acceptable form of birth control from the time of 
written or verbal assent to at least 14 days after the last dose of study drug has been taken. 
“Of childbearing potential” is defined in Section 12.9. Acceptable forms of birth control are 
listed in Section 10.3. 
4. Subject must be in general good health defined as the absence of any clinically relevant 
abnormalities as determined by the Investigator based on physical and neurological 
examinations, vital signs, ECGs, medical history, and clinical laboratory values 
(hematology, chemistry, and urinalysis) at Screening. If any of the hematology, chemistry, 
or urinalysis results are not within the laboratory's reference range, then the subject can be 
included only if the Investigator determines the deviations to be not clinically relevant. 
5. At least one parent/legal guardian of the subject must voluntary give written permission for 
him/her to participate in the study. 
6. Subject must give written or verbal assent prior to study participation. For verbal assent, the 
procedure will be documented and signed by a witness. A parent or guardian may not be the 
witness for a child's verbal assent document. 
7. Subject must meet Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition 
(DSM-5) criteria for a primary diagnosis of ADHD (combined, inattentive, or 
hyperactive/impulsive presentation) per clinical evaluation and confirmed by the Mini 
International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). If the 
MINI-KID assessment is available from a previous study with KP415, it does not need to 
be repeated. 
8. Subject must have a score of at least 3 (mildly ill) on the clinician-administered Clinical 
Global Impressions–Severity (CGI-S) scale at Visit 2. For subjects requiring washout of 
ADHD medications, this criterion refers to a score following washout. 
9. Subject must be able and willing to wash out current stimulant ADHD medications, 
including herbal medications from 5 days prior to the start of the Dose Optimization Phase 
(Visit 2), and abstain from taking these to the end of the Follow-Up Visit or Early 
Termination; and wash out non-stimulant ADHD medications from 14 days prior to the start 
of the Dose Optimization Phase (Visit 2), and abstain from taking these to the end of the 
Follow-Up Visit or Early Termination. 


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10. An ADHD-Rating Scale-5 (ADHD-RS-5) total score of at least 28 at Visit 2. For subjects 
requiring washout of ADHD medications, this criterion refers to a score following washout. 
11. Subject, subject’s parent/legal guardian and caregiver (if applicable) must understand and 
be willing and able to comply with all study procedures and visit schedule. If the subject is 
cared for by a caregiver for relevant parts of a school day, and if in this case, in the opinion 
of the Investigator, the caregiver of the subject is more suitable for certain assessments, the 
caregiver will need to agree to the applicable procedures and visits. 
12. Subject, parent/legal guardian and caregiver (if applicable) must be able to speak and 
understand English, and be able to communicate satisfactorily with the Investigator and 
study coordinator. 
13. Subject must be able to swallow size 3 capsules as demonstrated by easily swallowing a size 
3 placebo capsule at Screening, unless the subject participated in the KP415.E01 study 
previously, or unless the subjects agrees to take the contents of the capsule sprinkled on a 
small amount of apple sauce or in a small amount of water. 
7.2.3. Exclusion Criteria for Subjects Rolled Over from Study KP415.E01 
(To be evaluated at Screening Visit 1B, except when noted otherwise) 
A subject who meets any of the following exclusion criteria will not be enrolled into the study: 
1. If female, must not be pregnant or breastfeeding, and if of childbearing potential, must have 
a negative pregnancy test at the start of the Screening Phase (Visit 1B). In addition, a 
positive pregnancy test before the last dose of study drug will exclude a subject from further 
participation in the study. “Of childbearing potential” is defined in Section 12.9. 
2. Based on the medical history evaluated at Screening (Visit 1B), subject with any new 
clinically significant chronic medical condition that, in the judgment of the Investigator, 
may interfere with the participant's ability to participate in the study, or that may affect 
safety and/or the results of the study. 
3. In the opinion of the Investigator, subject has clinically significant suicidal 
ideation/behavior, based on history of attempted suicide and the C-SSRS assessment at 
Screening or at any time before the last dose of study drug. 
4. Subjects are using or planning to use prohibited drugs during the trial as specified in the 
protocol. 
5. Subject has a positive urine MPH screen at Visit 5. 


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6. Subject, parent/legal guardian and caregiver (if applicable at the Investigator’s discretion) 
has commitments during the study that would interfere with attending study visits. 
7. Subject or subject's family anticipates a move outside the geographic range of the 
investigative site during the study period, or plans extended travel inconsistent with the 
recommended visit interval during study duration. 
8. Subject is, in the opinion of the Investigator, unsuitable in any other way to participate in 
this study. 
7.2.4. Exclusion Criteria for New Subjects 
(To be evaluated at Screening Visit 1A, except when noted otherwise) 
A subject who meets any of the following exclusion criteria will not be enrolled into the study: 
1. Subjects who have received study drug (KP415 or placebo for KP415) in Study KP415.E01 
during the 45 days prior to the Treatment Phase. Subjects who have received KP415 in 
Study KP415.E01 less than 45 days prior to the Treatment Phase are eligible to be enrolled 
in the current study as roll-overs (but not as new subjects). 
2. If female, must not be pregnant or breastfeeding, and if of childbearing potential, must have 
a negative pregnancy test at the start of the Screening Phase (Visit 1A). In addition, a 
positive pregnancy test before the last dose of study drug will exclude a subject from further 
participation in the study. “Of childbearing potential” is defined in Section 12.9. 
3. Subject with any clinically significant chronic medical condition that, in the judgment of the 
Investigator, may interfere with the participant's ability to participate in the study. 
4. Subject has any diagnosis of bipolar I or II disorder, major depressive disorder, conduct 
disorder, obsessive-compulsive disorder, any history of psychosis, autism spectrum 
disorder, disruptive mood dysregulation disorder (DMDD), intellectual disability, Tourette's 
Syndrome, confirmed genetic disorder with cognitive and/or behavioral disturbances. 
Subjects with oppositional defiant disorder (ODD) are permitted to enroll in the study as 
long as ODD is not the primary focus of treatment, and, in the opinion of the Investigator, 
the ODD is mild to moderate, and eligible subjects with ODD are appropriate and 
cooperative during Screening. 
5. Subject has generalized anxiety disorder or panic disorder that has been the primary focus 
of treatment at any time during the 12 months prior to Screening or that has required 
pharmacotherapy any time during the 6 months prior to Screening. 
6. Subject has evidence of any chronic disease of the central nervous system (CNS) such as 


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tumors, inflammation, seizure disorder, vascular disorder, potential CNS related disorders 
that might occur in childhood (e.g., Duchenne Muscular dystrophy, myasthenia gravis, or 
other neurologic or serious neuromuscular disorders), or history of persistent neurological 
symptoms attributable to serious head injury. A past history of febrile seizure, drug-induced 
seizure, or alcohol withdrawal seizure is allowed. Subject taking anticonvulsants for seizure 
control currently or within the past 2 years before Screening are not eligible for study 
participation. 
7. Subject has a current (last month) psychiatric diagnosis other than specific phobia, motor 
skills disorders, oppositional defiant disorder, sleep disorders, elimination disorders, 
adjustment disorders, learning disorders, or communication disorders. Subjects allowed to 
enroll with any of these DSM disorders will require written justification from the 
Investigator documenting why the conditions will not interfere with participation and to 
emphasize that ADHD is the primary indication. 
8. In the opinion of the Investigator, subject has clinically significant suicidal 
ideation/behavior, based on a history of attempted suicide and the C-SSRS assessment at 
Screening or at any time before the last dose of study drug. 
9. Subject has any clinically significant unstable medical abnormality, chronic disease, or a 
history of a clinically significant abnormality of the cardiovascular (including 
cardiomyopathy, serious arrhythmias, structural cardiac disorders, or severe hypertension), 
gastrointestinal, respiratory, hepatic, or renal systems, or a disorder or history of a condition 
(e.g., malabsorption, gastrointestinal surgery) that may interfere with drug absorption, 
distribution, metabolism, or excretion of study drug. Active medical conditions that are 
minor or well-controlled are not exclusionary if they do not affect risk to the subject or the 
study results. In cases in which the impact of the condition upon risk to the subject or study 
results is unclear, the medical monitor should be consulted. Any subject with a known 
cardiovascular disease or condition (even if controlled) must be discussed with the medical 
monitor during Screening 
10. Subject has a history or presence of abnormal ECGs, which in the Investigator's opinion is 
clinically significant. 
11. Subject has a history of, or currently has a malignancy, except for non-melanomatous skin 
cancer. 
12. Subject has uncontrolled thyroid disorder as evidenced by thyroid stimulating hormone 
(TSH) ≤0.8 x the lower limit of normal (LLN) or ≥1.25 x the upper limit of normal (ULN) 
for the reference laboratory at Screening. For subjects who previously participated in Study 
KP415.E01, this condition does not need to be re-evaluated. 


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13. Subjects with a history of substance abuse or treatment (including alcohol) within 1 year 
prior to Screening. 
14. Subject shows evidence of substance or alcohol use or is currently using tobacco or other 
nicotine-containing products, or has a positive urine alcohol or urine drug screen at 
Screening. Subjects with a positive urine drug screen (including urine MPH screen) at 
Screening may be allowed to continue in the study, provided that the Investigator determines 
that the positive test is a result of taking prescribed medications, and subject is willing to 
wash out the current medication as required. 
15. Subject has participated in any other clinical study with an investigational drug/product 
within 90 days prior to Screening, or is currently participating in another clinical trial, with 
the exception of any trial with KP415, as follows: Subjects who participated in Study 
KP415.E01 and completed the last dose in Study KP415.E01 more than 45 days before the 
Treatment Phase in the current study, are eligible as new subjects in the current study. 
Subjects who completed other studies with KP415 (for example, the single-dose 
pharmacokinetic study KP415.105) may be enrolled in the current study as new subjects 
after a minimum 5-day washout period between the last dose of KP415 and Screening in the 
current study. 
16. Subject has taken ADHD medications from more than one class within 30 days prior to 
Screening. Subjects on a stable dose of one ADHD medication with occasional use of 
ADHD medications from another class are eligible at the discretion of the Investigator. 
17. Subjects with demonstrated lack of response or intolerability to adequate dose and duration 
of treatment with methylphenidate products. Judgment of adequate dose and duration is at 
the discretion of the Investigator. 
18. Subjects are using or planning to use prohibited drugs during the trial as specified in the 
protocol. 
19. Subject has a positive urine MPH screen at Visit 2. 
20. Subject has a history of severe allergies or adverse drug reactions to more than one class of 
medications. 
21. Subject has a history of allergic reaction or a known or suspected sensitivity to 
methylphenidate or any substance that is contained in the study drug. 
22. Subject, parent/legal guardian and caregiver (if applicable at the Investigator’s discretion) 
has commitments during the study that would interfere with attending study visits. 
23. Subject or subject's family anticipates a move outside the geographic range of the 


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investigative site during the study period, or plans extended travel inconsistent with the 
recommended visit interval during study duration. 
24. Subject is, in the opinion of the Investigator, unsuitable in any other way to participate in 
this study. 
7.2.5. Eligibility Criteria for Treatment Phase 
(To be evaluated at the end of the Dose Optimization Phase, for new subjects only) 
Subjects will need to meet the following additional eligibility criteria at the end of the Dose 
Optimization Phase in order to enter into the Treatment Phase: 
1. 
A reduction of ≥30% in ADHD-RS-5 from baseline (Visit 2) at the end of the Dose 
Optimization Phase. 
2. 
A CGI-I score of 1 or 2 at the end of the Dose Optimization Phase. 
3. 
Acceptable tolerability of the optimized KP415 dose experienced during the Dose 
Optimization Phase. 
8. STUDY TREATMENTS 
8.1. KP415 Dose Optimization (new subjects only) 
In the Dose Optimization Phase, daily treatments of 20, 30 and 40 mg open-label KP415 capsules 
will be administered (one capsule/day in the morning), for the titration to an optimal daily KP415 
dose based on tolerability and best individual dose-response in the opinion of the Investigator. Study 
drug will be taken orally in the morning at home or, at the visit days, may be taken at the study site. 
The capsule needs to be swallowed whole, or may be taken by sprinkling the contents of the capsule 
over a small amount of applesauce, or putting the contents in a small amount of water. See 
Appendix A for detailed instructions. Any of the methods of administration may be used on any 
day of the study. 
Subjects will begin taking open-label KP415 at home the morning following Visit 2. The starting 
dose of KP415 (Days 1-7 ±3 days) will be 30 mg/day. KP415 dose adjustments, if needed, will be 
performed at approximately weekly intervals between visits (at Visits 3 and 4). Actual visit dates 
may deviate from exactly being spaced 7 days apart such that the total duration of the Dose 
Optimization Phase ranges between 18 and 24 days (21 ±3 days). The daily doses of KP415 used 
in the Dose Optimization Phase will be 20, 30, and 40 mg (dose optimization range of ≥20 and ≤40 
mg). At Visits 3 and 4, based on the CGI scores, interview with the parent/guardian/caregiver, and 
safety data, the Investigator will evaluate the subject’s therapeutic responses and tolerability to 
treatment and decide whether the current KP415 dose should be increased, decreased, or remain the 


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same for the next week of dosing. If subjects experience symptoms of intolerance during the at-
home treatment, they must contact the clinical site, and, at the discretion of the Investigator, their 
KP415 dose may be adjusted before the next scheduled visit. Unscheduled visits between Visits 2, 
3, 4, and 5 are allowed as needed, at the discretion of the Investigator. 
At Visit 5 (start of the Treatment Phase), the Investigator will evaluate the eligibility criteria (see 
Section 7.2.5) for continuation into the Treatment Phase. For subjects eligible for the Treatment 
Phase, the optimal daily KP415 dose will be used as the daily KP415 dose during the Treatment 
Phase. 
8.2. Study Drug Administration in the Treatment Phase 
All subjects will be administered one unblinded KP415 capsule once daily in the Treatment Phase. 
The dose of KP415 will be determined by the optimal dose of KP415 at the end of the Dose 
Optimization Phase, either 20, 30, or 40 mg/day KP415. Study drug will be taken orally in the 
morning at home or, at the visit days, may be taken at the study site. The capsule needs to be 
swallowed whole, or may be taken by sprinkling the contents of the capsule over a small amount of 
applesauce, or putting the contents in a small amount of water. See Appendix A for detailed 
instructions. Any of the methods of administration may be used on any day of the study. 
8.3. Treatment Assignment 
Dose Optimization Phase (new subjects only): All eligible subjects will start on a dose of 30 
mg/day open-label KP415 and the KP415 dose will be titrated to either 20, 30 or 40 mg/day based 
on tolerability and best individual dose-response in the opinion of the Investigator. 
Treatment Phase (all subjects): Rolled-over subjects from Study KP415.E01, and new subjects 
who completed the Dose Optimization Phase (and passed the eligibility criteria for the Treatment 
Phase, Section 7.2.5), will be enrolled at Visit 5 (start of the Treatment Phase) for treatment with 
the optimized dose of KP415 capsules. During the Treatment Phase, at the Investigator’ discretion, 
based on individual tolerability and dose response, the daily dose of KP415 may be changed to any 
of the allowed dose levels (20, 30, or 40 mg/day). 
8.4. Blinding 
This is an open-label study. Study treatments will not be blinded. 
8.5. Compliance 
All study drug will be recorded by each site’s pharmacy staff member or Investigator-delegated 
employee. A record of the study drug accountability will be prepared and kept by the clinical site. 
Acceptable Compliance is defined as 80-100% (inclusive). If Compliance between subsequent 
scheduled visits of the Treatment Phase (Visits 6 through 16) is outside this acceptance range, or 


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cannot be determined (when, for example, the subject did not return unused study drug), the 
Investigator or designee will counsel the parent/legal guardian. If a subject is noncompliant more 
than once, the Investigator will discuss the subject’s noncompliance with the Medical Monitor. 
8.6. Study Stopping Rules 
The study will be stopped for any of the following reasons, whichever comes first: 
1. An interim analysis of the safety data will be conducted after approximately all subjects 
remaining in the study have completed 180 days (approximately 6 months) of treatment. 
After the completion of the interim analysis, based on the acceptance of the clinical and 
nonclinical safety database from the current study and other studies, the Sponsor may stop 
the study. Treatment in the current study will continue as planned while the interim analysis 
is conducted. If the decision is made to stop the study, all subjects remaining in the study 
will undergo the EOT Visit (with safety evaluations including fasting safety labs and ECGs) 
and a Follow-Up Visit. 
2. After all subjects have completed 360 days (approximately 1 year) of treatment.  
9. STUDY PROCEDURES 
For all subjects, the study will include a Screening Phase, Treatment Phase and a Follow-Up Visit. 
For new subjects only, after the Screening Phase and before entering the Treatment Phase, there 
will be a Dose Optimization Phase. Subjects rolled over from Study KP415.E01 (within the 45-day 
window) will have a Screening Visit followed by a Treatment Phase (no Dose Optimization Phase) 
because eligibility assessments and dose optimization were completed in Study KP415.E01. A table 
with the Schedule of Events (SOE) representing the required testing procedures to be performed is 
included in Section 1. Following is a list of these procedures and assessments: 
9.1. Screening Procedures (Visit 1A - New Subjects Only) 
The procedures at Screening are different between subjects rolled over from Study KP415.E01 and 
new subjects. Therefore, the Screening Visit for new subjects is designated Visit 1A (current 
section), and for roll-over subjects, is designated as Visit 1B (see Section 9.2). 
Subjects will complete the screening visit (Visit 1A) within 30 days of starting the Dose 
Optimization Phase (Visit 2). Prior to conducting any study-related activities including screening 
procedures, written or verbal assent and the Health Insurance Portability and Accountability Act 
(HIPAA) authorization must be signed and dated by the parent/legal guardian. 
The following procedures will be performed at the Screening Visit: 
1. Permission and HIPAA authorization by one parent/legal guardian of the subject. 


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2. Written or verbal assent by the subject. For verbal assent, the procedure will be 
documented and signed by a witness. A parent or guardian may not be the witness for 
a child's verbal assent document. 
3. ADHD Diagnosis and Confirmation based on the Statistical Manual of Mental 
Disorders - Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD 
(combined, inattentive, or hyperactive/impulsive presentation) and confirmed by the 
Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-
KID). 
4. Perform the clinician-administered Clinical Global Impressions–Severity (CGI-S) 
scale assessment. Subjects must have a CGI-S score of at least 3 (mildly ill) for further 
study participation. 
5. Subject demographics including date of birth, sex, race, and ethnicity. 
6. Administer a size 3 placebo capsule orally with up to 240 mL of water (Capsule 
Swallowing Test). The capsule may not contain any active drug substance. Subjects 
must be able to easily swallow the size 3 capsule to be eligible for further study 
participation. This is not required for subjects who have previously participated in the 
KP415.E01 study, or for subjects who are planning to take the study drug as the capsule 
contents sprinkled over a small amount of applesauce or added to a small amount of 
water. Subjects will be instructed how to take the study medication while at home. See 
Appendix A for detailed instructions. 
7. Review of inclusion/exclusion criteria to determine study eligibility. 
8. Record medical history including chronic conditions, relevant surgical procedures 
(with start date), medications, and history of alcohol and recreational drug use. 
9. A complete physical examination. 
10. Body weight, height, and BMI. 
11. Vital signs after a minimum of 3 minutes of rest (respiratory rate, pulse rate, blood 
pressure, and oral temperature). 
12. Perform the Columbia Suicide Severity Rating Scale (C-SSRS) assessment, 
“Children’s Baseline/Screening” version. Subjects with clinically significant suicidal 
ideation/behavior, in the opinion of the Investigator, based on a history of attempted 
suicide and the C-SSRS assessment, will be excluded from enrollment in the study, and 
further evaluation and/or preventive intervention steps for suicidal behavior will be 
taken, at the discretion of the Investigator. 


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13. 12-lead electrocardiogram (ECG) after subject has been in supine position for a 
minimum of 3 minutes. 
14. Clinical laboratory tests (chemistry, hematology and urinalysis) will be obtained under 
fasting conditions. Clinical laboratory measurements may be repeated at the discretion 
of the Investigator. 
15. At Screening, urine samples will be tested for alcohol and drugs of abuse 
(amphetamines, methamphetamines, benzodiazepines, barbiturates, cannabinoids, 
cocaine, opioids including oxycodone). If the urine test is positive for alcohol or drugs 
of abuse at Screening, the subject will be excluded from study participation, with the 
exception of the following: Depending on a subject's current ADHD medication at 
Screening, the urine screen at Screening may test positive for ADHD medications such 
as amphetamines and methamphetamines. All ADHD medications must be washed out 
by Visit 2. Subjects with a positive MPH urine screen at Visit 2 will be excluded from 
further participation in the study or may be retested at a later date, and may be enrolled 
if the MPH urine screen retest is negative, as long as the Screening Window is adhered 
to. 
16. At Screening, urine samples will be tested for methylphenidate. If the urine test is 
positive for methylphenidate at Screening, the subject will be excluded from study 
participation, with the exception of the following: Depending on a subject's current 
ADHD medication at Screening, the urine screen at Screening may test positive for 
methylphenidate. All ADHD medications must be washed out by Visit 2. 
17. Serum β-human chorionic gonadotropin (β-hCG) pregnancy test for all female subjects 
of childbearing potential. See Section 12.9 for the definition of childbearing potential. 
A positive pregnancy test will exclude a subject from further participation in the study. 
18. Review of concomitant medications, treatment and/or therapies including treatment for 
ADHD. 
After subjects complete the screening procedures and are considered eligible to take part in the 
clinical study, they will be instructed to return to the clinic at Visit 2 to begin the Dose Optimization 
Phase. In addition, if applicable, they will be given the date on which to begin wash out of any 
ADHD and other medications prior to Visit 2. See Section 10.2 for the medications that are 
prohibited and their associated time frames, including the days that they are prohibited before Visit 
2, i.e., washout days for subjects taking the medications. 
Before or on the day during the screening period that subjects will need to start the washout of their 
ADHD medications (for example, 5 days before Visit 2 for stimulants), study site staff will contact 
the subject’s parent/guardian by phone to remind them of the washout (“washout phone call”). 


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Rescreening: New subjects who are screened outside the screening window may be rescreened for 
participation at a later time. New subjects who received any dose of study drug and are terminated 
early or are not eligible to continue in the Treatment Phase, are not eligible to participate later in 
the study (and will not be rescreened). 
9.2. Screening Procedures (Visit 1B - Rolled-Over Subjects Only) 
The procedures at Screening are different between subjects rolled over from Study KP415.E01 and 
new subjects. Therefore, the Screening Visit for rolled-over subjects is designated as Visit 1B 
(current section), and for new subjects is designated Visit 1A (see Section 9.1). 
Screening Window:  
The Screening Visit for rolled-over subjects (Visit 1B) may occur on the same day as the EOS (Visit 
7, Follow-Up) in Study KP415.E01, or later, and must occur within 30 days before Visit 5 in the 
current study. The roll-over window (for Rolled-Over Subjects), dose-to-dose between both studies 
(i.e., gap between the last dose in Study KP415.E01 [Visit 6] and the fist dose in the current study 
[Visit 5]) is maximum 45 days. 
Prior to conducting any study-related activities including screening procedures, written or verbal 
assent and the Health Insurance Portability and Accountability Act (HIPAA) authorization must be 
signed and dated by the parent/legal guardian. 
The following procedures will be performed at the Screening Visit: 
1. Permission and HIPAA authorization by one parent/legal guardian of the subject. 
2. Written or verbal assent by the subject. For verbal assent, the procedure will be 
documented and signed by a witness. A parent or guardian may not be the witness for 
a child's verbal assent document. 
3. Subject demographics including date of birth, sex, race, and ethnicity. 
4. Review of inclusion/exclusion criteria to determine study eligibility, including the 
successful completion of Study KP415.E01. 
5. Record medical history including chronic conditions, relevant surgical procedures 
(with start date), medications, and history of alcohol and recreational drug use. 
6. As part of Medical History (and with more details captured in the database), record 
treatment with study drug in Study KP415.E01 with regards to dose, duration, date of 
last dose (Visit 6 in Study KP415.E01), last visit in Study KP415.E01 (Visit 7 in Study 
KP415.E01), etc. 
7. A complete physical examination. 


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8. Body weight, height, and BMI. 
9. Vital signs after a minimum of 3 minutes of rest (respiratory rate, pulse rate, blood 
pressure, and oral temperature). 
10. Perform the C-SSRS assessment, “Children’s Baseline/Screening” version. Subjects 
with clinically significant suicidal ideation/behavior, in the opinion of the Investigator, 
based on a history of attempted suicide and the C-SSRS assessment, will be excluded 
from enrollment in the study, and further evaluation and/or preventive intervention 
steps for suicidal behavior will be taken, at the discretion of the Investigator. For roll-
over subjects, if the Screening Visit (Visit 1B) occurs on the same day as the Follow-
Up Visit (Visit 7) of Study KP415.E01, one C-SSRS will be obtained to be used in both 
studies. If Visit 1B occurs later, after Visit 7 in E01, a new C-SSRS will be obtained at 
Visit 1B for the current study. 
11. 12-lead ECG after subject has been in supine position for a minimum of 3 minutes. For 
roll-over subjects, if the Screening Visit (Visit 1B) occurs on the same day as the 
Follow-Up Visit (Visit 7) of Study KP415.E01, one ECG will be obtained to be used 
in both studies. If Visit 1B occurs later, after Visit 7 in E01, a new ECG will be obtained 
at Visit 1B as baseline for the current study. 
12. Clinical laboratory tests (chemistry, hematology and urinalysis) will be obtained under 
fasting conditions (or under non-fasting conditions for the special case explained 
below). For roll-over subjects, the Investigator has the option to use the clinical 
laboratory results from the Follow-Up Visit in Study KP415.E01 (Visit 7) in lieu of 
collecting new blood samples at Screening (Visit 1B) in the current study, as long as 
the clinical laboratory samples from the E01 study were collected within 30 days prior 
to Visit 1B. If clinical laboratory measurements from Visit 7 of study KP415.E01 are 
being utilized, then fasting is not required; however, the site must record whether the 
samples were collected under fasting/non-fasting conditions. Clinical laboratory 
measurements may be repeated at the discretion of the Investigator. 
13. At Screening, urine samples will be tested for alcohol and drugs of abuse 
(amphetamines, methamphetamines, benzodiazepines, barbiturates, cannabinoids, 
cocaine, opioids including oxycodone). If the urine test is positive for alcohol or drugs 
of abuse at Screening, the subject will be excluded from study participation, with the 
exception of the following: Depending on a subject's current ADHD medication at 
Screening, the urine screen at Screening may test positive for ADHD medications such 
as amphetamines and methamphetamines. All ADHD medications must be washed out 
by Visit 5 (rolled-over subjects will not have Visits 2, 3 and 4), and the urine test must 
be negative for further study participation. 


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14. Serum β-hCG pregnancy test for all female subjects of childbearing potential. See 
Section 12.9 for the definition of childbearing potential. A positive pregnancy test will 
exclude a subject from further participation in the study. 
15. Subjects will be instructed how to take the study medication at home. The capsule 
needs to be swallowed whole, or may be taken by sprinkling the contents of the capsule 
over a small amount of applesauce, or putting the contents in a small amount of water. 
See Appendix A for detailed instructions. Any of the methods of administration may 
be used on any day of the study. 
After roll-over subjects complete the screening procedures and are considered eligible to take part 
in the clinical study, they will be instructed to return to the clinic at Visit 5 to begin the Treatment 
Phase. Visits 2, 3, and 4 are not needed for subjects rolled over from Study KP415.E01 because 
their optimum dose was determined in the Dose Optimization Phase of Study KP415.E01. 
Therefore, rolled-over subjects from Study KP415.E01 will start with Visit 1B as the first visit of 
the current study, followed by Visit 5 as the next visit (rolled-over subjects will not have Visits 2, 
3 and 4). 
If applicable, roll-over subjects will be given the date on which to begin wash out of any ADHD 
and other medications prior to Visit 5. See Section 10.1 for the medications that are prohibited and 
their associated time frames, including the days that they are prohibited before Visit 5, i.e., washout 
days for subjects taking the medications. 
Before or on the day during the screening period that subjects will need to start the washout of their 
ADHD medications (for example, 5 days before Visit 5 for stimulants), study site staff will contact 
the subject’s parent/guardian by phone to remind them of the washout (“washout phone call”). 
Rescreening: Subjects that successfully completed Study KP415.E01 but are unable to be screened 
within the screening window for roll-over subjects may be screened as new subjects. Rolled-over 
subjects who received any dose of study drug in the current study but are terminated early, are not 
eligible to participate later in the study (and will not be rescreened). 
9.3. Dose Optimization Phase (Visit 2-4; New Subjects Only) 
Subjects who meet the inclusion/exclusion criteria during Screening, will enter into the Dose 
Optimization Phase (Visits 2, 3, and 4). The subjects will undergo the following procedures during 
these visits. 
9.3.1. Visit 2 
The following procedures will be performed at Visit 2: 
1. Review of inclusion/exclusion criteria to determine whether subjects continue to meet 


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study eligibility. 
2. Update medical history. 
3. Vital signs after a minimum of 3 minutes of rest (respiratory rate, pulse rate, blood 
pressure, and oral temperature). 
4. Perform the C-SSRS, “Children’s Since Last Visit” version. Subjects with clinically 
significant suicidal ideation/behavior, in the opinion of the Investigator, based on the C-
SSRS assessment, will be excluded from further participation in the study, and further 
evaluation and/or preventive intervention steps for suicidal behavior will be taken, at the 
discretion of the Investigator. 
5. Perform the ADHD-RS-5 score assessment (baseline assessment). Subjects needs to 
have an ADHD-RS-5 total score of at least 28 for further study participation. For 
subjects requiring washout of ADHD medications, this criterion refers to a score 
following washout of at least 5 days. 
6. Perform the clinician-administered CGI-S scale assessment (baseline assessment). 
Subjects must have a CGI-S score of at least 3 (mildly ill) for further study participation. 
For subjects requiring washout of ADHD medications, this criterion refers to a score 
following washout of at least 5 days. 
7. Perform the CSHQ. The Investigator or designee will fill in the CSHQ questionnaire 
based on an interview with the parent/guardian/caregiver. For subjects requiring 
washout of ADHD medications, the scoring will be based on the subject’s sleep behavior 
on the days after washout for at least 5 days before Visit 2. 
8. Urine Screen for MPH: Urine samples will be tested for MPH at Visit 2 for new subjects. 
A urine dipstick (e.g., NarcoCheck®) will be used to screen for the presence of MPH in 
the urine. All ADHD medications must be washed out by Visit 2 (MPH urine screen 
must test negative). New subjects with a positive MPH urine screen at Visit 2 will be 
excluded from further participation in the study or may be retested at a later date, and 
may be enrolled if the MPH urine screen retest is negative, as long as the Screening 
Window is adhered to. 
9. Urine pregnancy test for all female subjects of childbearing potential. See Section 12.9 
for the definition of childbearing potential. A positive pregnancy test at Screening will 
exclude a subject from further participation in the study. 
10. Review of concomitant medications, treatment and/or therapies. 
11. Provide subject with the starting dose of 30 mg KP415 capsules to begin the Dose 


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Optimization Phase (Days 1-7 ±3 days). KP415 dose adjustments, if needed, will be 
performed at approximately weekly intervals between visits (at Visits 3 and 4). Actual 
visit dates may deviate from exactly being spaced 7 days apart such that the total 
duration of the Dose Optimization Phase ranges between 18 and 24 days (21 ±3 days). 
Subjects will be instructed to take study drug every morning while at home under the 
supervision of their parent/legal guardian/caregiver. The capsule needs to be swallowed 
whole, or may be taken by sprinkling the contents of the capsule over a small amount of 
applesauce, or putting the contents in a small amount of water. See Appendix A for 
detailed instructions. Any of the methods of administration may be used on any day of 
the study. 
9.3.2. Visit 3 (Day 7 ±3 days) 
The following procedures will be performed at Visit 3: 
1. Record the number of returned and administered capsules of unblinded study drug for 
drug accountability and compliance (See Section 8.5). 
2. Review of inclusion/exclusion criteria to determine whether subjects continue to meet 
study eligibility. 
3. Update medical history. 
4. Vital signs after a minimum of 3 minutes of rest (respiratory rate, pulse rate, blood 
pressure, and oral temperature). 
5. Perform the C-SSRS, “Children’s Since Last Visit” version. Subjects with clinically 
significant suicidal ideation, in the opinion of the Investigator, based on the C-SSRS 
assessment, will be excluded from further participation in the study, and further 
evaluation and/or preventive intervention steps for suicidal behavior will be taken, at the 
discretion of the Investigator. 
6. Perform the ADHD-RS-5 score assessment. 
7. Perform the clinician-administered CGI-S scale assessment. 
8. Perform the CGI-I scale assessment. 
9. KP415 dosing and dose adjustments, if needed, will be performed at weekly intervals ± 
3 days. At Visit 3 based on the CGI, interview with the parent/guardian/caregiver, and 
safety data, the Investigator will evaluate the subject’s therapeutic responses and 
tolerability to treatment, and decide whether the current KP415 dose should be 
increased, decreased, or remain the same for the next week of titration. At any day during 


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the Dose Optimization Phase, the daily dose will be either 20, 30 or 40 mg KP415 
capsules. Subjects will be instructed to take study drug every morning while at home. 
The capsule needs to be swallowed whole, or may be taken by sprinkling the contents 
of the capsule over a small amount of applesauce, or putting the contents in a small 
amount of water. See Appendix A for detailed instructions. Any of the methods of 
administration may be used on any day of the study. 
10. Assessment and review of Adverse Events, and the subject’s parent/guardian will be 
instructed to contact the study site for the reporting of AEs during the dosing periods at 
home. 
11. Review of concomitant medications, treatment and/or therapies. 
9.3.3. Visit 4 (Day 14 ±3 days) 
The following procedures will be performed at Visit 4: 
1. Record the number of returned and administered capsules of unblinded study drug for 
drug accountability and compliance. 
2. Review of inclusion/exclusion criteria to determine whether subjects continue to meet 
study eligibility. 
3. Update medical history. 
4. Vital signs after a minimum of 3 minutes of rest (respiratory rate, pulse rate, blood 
pressure, and oral temperature). 
5. Perform the C-SSRS, “Children’s Since Last Visit” version. Subjects with clinically 
significant suicidal ideation, in the opinion of the Investigator, based on the C-SSRS 
assessment, will be excluded from further participation in the study, and further 
evaluation and/or preventive intervention steps for suicidal behavior will be taken, at the 
discretion of the Investigator. 
6. Perform the ADHD-RS-5 score assessment. This assessment may be obtained by phone 
within 48 hours before the visit. 
7. Perform the clinician-administered CGI-S scale assessment. This assessment may be 
obtained by phone within 48 hours before the visit. 
8. Perform the CGI-I scale assessment. This assessment may be obtained by phone within 
48 hours before the visit. 
9. KP415 dosing and dose adjustments, if needed, will be performed at weekly intervals 


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±3 days. At Visit 4, based on the CGI, interview with the parent/guardian/caregiver, and 
safety data, the Investigator will evaluate the subject’s therapeutic responses and 
tolerability to treatment, and decide whether the current KP415 dose should be 
increased, decreased, or remain the same for the next week of titration. At any day during 
the Dose Optimization Phase, the daily dose will be either 20, 30 or 40 mg KP415 
capsules. Subjects will be instructed to take study drug every morning while at home 
under the supervision of their parent/legal guardian/caregiver. Additional water may be 
given if needed. The capsule needs to be swallowed whole, or may be taken by 
sprinkling the contents of the capsule over a small amount of applesauce, or putting the 
contents in a small amount of water. See Appendix A for detailed instructions. Any of 
the methods of administration may be used on any day of the study. 
10. Assessment and review of Adverse Events, and the subject’s parent/guardian will be 
instructed to contact the study site for the reporting of AEs during the dosing periods at 
home. 
11. Review of concomitant medications, treatment and/or therapies. 
9.4. Treatment Phase (Visits 5 to 17; All Subjects) 
Subjects who meet the inclusion/exclusion criteria will enter into the Treatment Phase (Visits 5-
17). The subjects will undergo the following procedures during these visits. 
9.4.1. Visit 5 
Rolled-over subjects who have taken ADHD medications (other than study drug in Study 
KP415.E01) between KP451.E01 and Visit 5 of the current study, will need to wash out their ADHD 
medications for at least 5 days before Visit 5. For these subjects, if possible, study site staff will 
contact the parent/guardian 5 days before Visit 5 to remind them that subjects must abstain of taking 
study drug on the 5 days before Visit 5. 
The following procedures will be performed at Visit 5: 
1. If applicable, record the number of returned and administered capsules of unblinded 
study drug for drug accountability and compliance. This only applies to new subjects 
who received study drug at home between Visits 4 and 5, as part of the Dose 
Optimization Phase. 
2. Review of inclusion/exclusion criteria to determine whether subjects continue to meet 
study eligibility. 
 
3. Update medical history. 


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4. Body weight, height, and BMI. 
5. Vital signs after a minimum of 3 minutes of rest (respiratory rate, pulse rate, blood 
pressure, and oral temperature). 
6. Urine Screen for MPH (roll-over subjects only): Urine samples will be tested for MPH 
at Visit 5 for roll-over subjects. A urine dipstick (e.g., NarcoCheck®) will be used to 
screen for the presence of MPH in the urine. All ADHD medications must be washed 
out by Visit 5 for roll-over subjects (new subjects will not be tested since they will have 
received study drug in the preceding Dose Optimization Phase). Roll-over subjects with 
a positive MPH urine screen at Visit 5 will be excluded from further participation in the 
study or may be retested at a later date, and may be enrolled if the MPH urine screen 
retest is negative, as long as the Screening Window is adhered to. 
7. Urine pregnancy test for all female subjects of childbearing potential. See Section 12.9 
for the definition of childbearing potential. A positive pregnancy test will exclude a 
subject from further participation in the study. 
8. Perform the C-SSRS assessment, “Children’s Since Last Visit” version. Subjects with 
clinically significant suicidal ideation/behavior, in the opinion of the Investigator, based 
on the C-SSRS assessment, will be excluded from further participation in the study, and 
further evaluation and/or preventive intervention steps for suicidal behavior will be 
taken, at the discretion of the Investigator. 
9. Perform the ADHD-RS-5 score assessment. 
10. Perform the clinician-administered CGI-S scale assessment. 
11. For new subjects only, perform the CGI-I scale assessment. This assessment at the end 
of the Dose Optimization Phase is used to evaluate eligibility criteria for the Treatment 
Phase of new subjects (see Section 7.2.5). 
12. Perform the CSHQ. The Investigator or designee will fill in the CSHQ questionnaire 
based on an interview with the parent/guardian/caregiver. The scoring will be based on 
the subject’s sleep behavior on the days before Visit 5 (and after washout of ADHD 
medications, if applicable). This assessment will be used as the baseline to assess sleep 
behavior. 
13. For new subjects only, the Investigator will evaluate the eligibility criteria (see Section 
7.2.5) based on the data from the Dose Optimization Phase for continuation into the 
Treatment Phase. For subjects eligible for the Treatment Phase, the previously 
determined optimal daily KP415 dose will be used as the daily KP415 dose in the 
Treatment Phase. 


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14. Eligible subjects will be enrolled in the Treatment Phase, and their appropriate dose of 
unblinded study drug (KP415 capsules) to be taken at home once-a-day in the morning 
on each of the following 30 days (Days 1-30 ±5 days) will be dispensed to the subjects. 
Subjects will be instructed to take study drug every morning while at home under the 
supervision of their parent/legal guardian/caregiver. The capsule needs to be swallowed 
whole, or may be taken by sprinkling the contents of the capsule over a small amount of 
applesauce, or putting the contents in a small amount of water. See Appendix A for 
detailed instructions. Any of the methods of administration may be used on any day of 
the study. 
15. Assessment and review of Adverse Events, and the subject’s parent/guardian will be 
instructed to contact the study site for the reporting of AEs during the dosing periods at 
home. 
16. Review of concomitant medications, treatment and/or therapies. 
9.4.2. Treatment During At Home Periods 
On days of the Treatment Phase between visits, subjects will take unblinded study drug at home 
under supervision of parent or legal guardian. Study drug will be taken daily in the morning while 
at home. The capsule needs to be swallowed whole, or may be taken by sprinkling the contents of 
the capsule over a small amount of applesauce, or putting the contents in a small amount of water. 
See Appendix A for detailed instructions. Any of the methods of administration may be used on 
any day of the study. 
Subject’s parent/guardian will contact the study site for the reporting of AEs during the dosing 
periods at home. Subjects will need to adhere to all medication restrictions and general restrictions 
(see Section 10). 
9.4.3. Visit 6 through Visit 16 
The following procedures will be performed during each of the Visits 6-16 (inclusive), except when 
noted otherwise: 
1. Record the number of returned and administered capsules of unblinded study drug for 
drug accountability and compliance (See Section 8.5). 
2. Update medical history. 
3. A complete physical examination (at Visit 11 only). 
4. Body weight, height, and BMI. 


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5. Vital signs after a minimum of 3 minutes of rest (respiratory rate, pulse rate, blood 
pressure, and oral temperature). 
6. 12-lead ECG after subject has been in supine position for a minimum of 3 minutes (at 
Visit 11 only). 
7. Clinical laboratory tests (chemistry, hematology and urinalysis) (at Visit 11 only) under 
fasting conditions. 
8. Perform the C-SSRS assessment, “Children’s Since Last Visit” version. Subjects with 
clinically significant suicidal ideation, in the opinion of the Investigator, based on the 
C-SSRS assessment, will be excluded from further participation in the study, and further 
evaluation and/or preventive intervention steps for suicidal behavior will be taken, at the 
discretion of the Investigator. 
9. Urine pregnancy test for all female subjects of childbearing potential. See Section 12.9 
for the definition of childbearing potential. A positive pregnancy test will exclude a 
subject from further participation in the study. 
10. Perform the ADHD-RS-5 score assessment. 
11. Perform the clinician-administered CGI-S scale assessment. 
12. Perform the CSHQ. The Investigator or designee will fill in the CSHQ questionnaire 
based on an interview with the parent/guardian/caregiver. 
13. If needed, perform a KP415 dose adjustments: based on the CGI-S, interview with the 
parent/guardian/caregiver, and safety data, the Investigator will evaluate the subject’s 
therapeutic responses and tolerability to treatment, and decide whether the current 
KP415 dose should be increased, decreased, or remain the same. At any day during the 
Treatment Phase, the daily dose will be either 20, 30 or 40 mg KP415 capsules. 
14. Stimulant ADHD medications (with the exception of study drug), including herbal 
medications, are prohibited from 5 days prior to Visit 5 to the end of the Follow-Up 
Visit or Early Termination Visit. Non-Stimulant ADHD medications are prohibited 
from 14 days prior to the start of Visit 5 to the end of the Follow-Up Visit or Early 
Termination Visit. Other prohibited medications with their associated time windows 
when they are prohibited are listed in Section 10. 
15. The appropriate dose of unblinded study drug (KP415) to be taken at home once-a-day 
in the morning on each day until the next visit will be dispensed to the subjects. 
16. Assessment and review of Adverse Events, and the subject’s parent/guardian will be 


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instructed to contact the study site for the reporting of AEs during the dosing periods at 
home. 
17. Review of concomitant medications, treatment and/or therapies. 
9.4.4. Visit 17 (EOT Visit) 
The following procedures will be performed at the End-of-Treatment Visit (EOT, Visit 17) after 
administration of the last dose of study drug: 
1. Record the number of returned and administered capsules of unblinded study drug for 
drug accountability and compliance. 
2. Update medical history. 
3. A complete physical examination. 
4. Body weight, height, and BMI. 
5. Vital signs after a minimum of 3 minutes of rest (respiratory rate, pulse rate, blood 
pressure, and oral temperature). 
6. 12-lead ECG after subject has been in supine position for a minimum of 3 minutes. 
7. Clinical laboratory tests (chemistry, hematology and urinalysis) under fasting 
conditions. 
8. Urine pregnancy test for all female subjects of childbearing potential. See Section 12.9 
for the definition of childbearing potential. 
9. Perform the C-SSRS assessment, “Children’s Since Last Visit” version. If a subject has 
clinically significant suicidal ideation, in the opinion of the Investigator, based on the 
C-SSRS assessment, further evaluation and/or preventive intervention steps for suicidal 
behavior will be taken, at the discretion of the Investigator. 
10. Perform the ADHD-RS-5 score assessment. 
11. Perform the clinician-administered CGI-S scale assessment. 
12. Perform the CSHQ. The Investigator or designee will fill in the CSHQ questionnaire 
based on an interview with the parent/guardian/caregiver. 
13. Stimulant ADHD medications (with the exception of study drug), including herbal 
medications, are prohibited from 5 days prior to Visit 5 to the end of the Follow-Up 


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Visit or Early Termination Visit. Non-Stimulant ADHD medications are prohibited 
from 14 days prior to the start of Visit 5 to the end of the Follow-Up Visit or Early 
Termination Visit. Other prohibited medications with their associated time windows 
when they are prohibited are listed in Section 10. 
14. Assessment and review of Adverse Events. 
15. Review of concomitant medications, treatment and/or therapies. 
9.5. Unscheduled Visits 
At the discretion of the Investigator, subjects may be asked to come to the clinical site for an 
unscheduled visit. Subjects will need to bring their unused study drug to the visit. 
Unscheduled visits can occur at any time during the Dose Optimization Phase (new subjects only) 
or the Treatment Phase. Examples of reasons to conduct an unscheduled visit: 
• If subjects experience an Adverse Event during the at-home treatment, they must contact 
the clinical site, and, at the discretion of the Investigator, further in-person medical 
evaluation and review may be performed. 
• If subjects experience symptoms of intolerance during the at-home treatment with study 
drug or have complaints about increases in ADHD symptoms, they must contact the clinical 
site, and, at the discretion of the Investigator, their KP415 dose may be adjusted before the 
next scheduled visit. 
The following procedures will occur at the Unscheduled Visit: 
1. Record the number of administered capsules of unblinded study drug for drug 
accountability and compliance. For this purpose, subjects will be asked to bring their 
unused medication to the clinical site. 
2. Vital signs after a minimum of 3 minutes of rest (respiratory rate, pulse rate, blood 
pressure, and oral temperature). 
3. Assessment and review of Adverse Events. 
4. Review of concomitant medications, treatment and/or therapies. 
The following procedures will occur at the Unscheduled Visit, each at the discretion of the 
Investigator: 
1. Evaluations for safety, as needed (for example, to evaluate and review Adverse Events): 


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a. Physical examination 
b. 12-lead ECG after subject has been in supine position for a minimum of 3 
minutes 
c. C-SSRS, “Children’s Since Last Visit” version. Subjects with clinically 
significant suicidal ideation/behavior, in the opinion of the Investigator, based 
on the C-SSRS assessment, will be excluded from further participation in the 
study, and further evaluation and/or preventive intervention steps for suicidal 
behavior will be taken, at the discretion of the Investigator. 
d. Clinical laboratory assessments 
2. If, at the discretion of the Investigator, an unscheduled evaluation of the changes in 
ADHD symptoms is needed, for a potential unscheduled dose level change of study 
drug: 
a. If needed, perform an assessment of ADHD severity. This may include an 
ADHD-RS-5 and/or CGI-S scale assessment, and/or, during the Dose 
Optimization Phase (new subjects only), a CGI-I scale assessment. 
b. If needed, perform a KP415 dose adjustment: based on the ADHD severity 
assessment, interview with the parent/guardian/caregiver, and safety data, the 
Investigator will evaluate the subject’s therapeutic response and tolerability to 
treatment, and decide whether the current KP415 dose should be increased, 
decreased, or remain the same. On any day during the study, the daily dose will 
be either 20, 30 or 40 mg KP415 capsules. See Section 11.5.4 for drug 
dispensing and drug return procedures at unscheduled visits. 
If a subject meets any of the withdrawal criteria during the Unscheduled Visit, the subject will be 
withdrawn, and Early Termination procedures will be completed (see Section 9.6). 
9.6. Early Termination Visit 
Early Termination (ET) from the study is defined as withdrawal during the Dose Optimization 
Phase (new subjects only) or Treatment Phase (all subjects) after at least one dose of study drug is 
administered. For subjects who withdraw early from the study, the Investigator should make every 
effort to perform all ET procedures before discharging the subject from the research clinic. 
The following procedures will be performed at ET visits: 
1. If appropriate, record the number of returned and administered capsules of unblinded study 
drug for drug accountability and compliance. 
2. Update medical history. 
3. Complete physical examination. 


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4. Body weight, height, and BMI. 
5. Vital signs (respiratory rate, pulse rate, blood pressure, and oral temperature) after subject 
has been sitting for a minimum of 3 minutes. 
6. 12-lead ECG after subject has been in supine position for a minimum of 3 minutes. 
7. Clinical laboratory tests (chemistry, hematology and urinalysis). 
8. Urine pregnancy test for all female subjects of childbearing potential. See Section 12.9 for 
the definition of childbearing potential. 
9. Assessment of the C-SSRS, “Children’s Since Last Visit” version. If a subject has, in the 
opinion of the Investigator, clinically significant suicidal ideation/behavior, based on the C-
SSRS assessment, further evaluation and/or preventive intervention steps for suicidal 
behavior will be taken, at the discretion of the Investigator. 
10. Stimulant ADHD medications (with the exception of study drug), including herbal 
medications, are prohibited from 5 days prior to Visit 5 to the end of the Follow-Up Visit or 
Early Termination Visit. Non-Stimulant ADHD medications are prohibited from 14 days 
prior to the start of Visit 5 to the end of the Follow-Up Visit or Early Termination Visit. 
Other prohibited medications with their associated time windows when they are prohibited 
are listed in Section 10. 
11. Review of concomitant medications, treatment and/or therapies. 
12. Assessment and review of Adverse Events. 
At the discretion of the Investigator, ensuring the safety of the subjects, any ET procedures that 
were already performed on the same day as part of the study phase from where the subject enters 
ET, do not need to be repeated. 
Subjects will be discharged from the study clinic when the Investigator determines that the subjects 
are medically stable and, if possible, after all ET procedures are completed. 
Subjects who withdraw early from the study and complete the above ET procedures will not return 
for a Follow-Up Visit. Therefore, the ET Visit is the EOS for these subjects. 
9.7. Follow-Up Visit 
Subjects who complete the Treatment Phase will return in 3 ±2 days after the administration of the 
last dose of study drug for the Follow-Up Visit. 
The following procedures will be completed during the Follow-Up Visit: 


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1. Update medical history. 
2. Body weight, height, and BMI. 
3. Vital signs after a minimum of 3 minutes of rest (respiratory rate, pulse rate, blood pressure, 
and oral temperature). 
4. Urine pregnancy test for all female subjects of childbearing potential. See Section 12.9 for 
the definition of childbearing potential. 
5. Assessment of the C-SSRS, “Children’s Since Last Visit” version. If a subject has, in the 
opinion of the Investigator, clinically significant suicidal ideation/behavior, based on the C-
SSRS assessment, further evaluation and/or preventive intervention steps for suicidal 
behavior will be taken, at the discretion of the Investigator. 
6. Stimulant ADHD medications (with the exception of study drug), including herbal 
medications, are prohibited from 5 days prior to Visit 5 to the end of the Follow-Up Visit or 
Early Termination Visit. Non-Stimulant ADHD medications are prohibited from 14 days 
prior to the start of Visit 5 to the end of the Follow-Up Visit or Early Termination Visit. 
Other prohibited medications with their associated time windows when they are prohibited 
are listed in Section 10. 
7. Review of concomitant medications, treatment and/or therapies. 
8. Assessment and review of adverse events. 
The Follow-Up Visit is the EOS for subjects who will undergo the Follow-Up procedures. 
9.8. End of Study (EOS) 
The End of Study (EOS) is either the Follow-Up Visit for subjects who complete the Treatment 
Phase, or the Early Termination Visit for subjects who withdraw early from the study. 
10. CONCOMITANT MEDICATIONS AND RESTRICTIONS 
Subjects will adhere to the following restrictions before and after administration of study drug, as 
specified: 
10.1. Medication Restrictions for Rolled-Over Subjects 
Rolled-over subjects will be prohibited/limited to receive certain medications in the trial, as follows: 
• Stimulant ADHD medications (with the exception of study drug), including herbal 
medications, are prohibited from 5 days prior to the start of the Treatment Phase (Visit 5) to 


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the end of the Follow-Up Visit or Early Termination Visit. These include: methylphenidate, 
amphetamine, Ritalin®, Ritalin® SR, Metadate® ER, Concerta®, dextromethylphenidate, 
Focalin®, dextroamphetamine, Dexedrine®, Adderall®. 
• Non-Stimulant ADHD medications are prohibited from 14 days prior to the start of the 
Treatment Phase (Visit 5) to the end of the Follow-Up Visit or Early Termination Visit. 
These include: Atomoxetine, guanfacine, clonidine; and SSRIs such as fluoxetine and 
paroxetine. 
• The following medications are prohibited from 14 days prior to the start of the Treatment 
Phase (Visit 5) to the end of the Follow-Up Visit or Early Termination Visit: 
o Tricyclic antidepressants. 
o Monoamine oxidase inhibitors (MAOIs). 
o Mood stabilizers (e.g., lithium, valproate, quetiapine). 
o Antipsychotics (e.g., risperidone, olanzapine). 
o Coumarin anticoagulants. 
o Anticonvulsants. 
o Halogenated anesthetics. 
o Phenylbutazone 
 
• Sedative hypnotics/sleep enhancers (with the exception of melatonin) are prohibited from 
14 days prior to the start of the Treatment Phase (Visit 5) to the end of the Follow-Up Visit 
or Early Termination Visit. 
• Melatonin is allowed if subjects have taken it for more than 30 days before the start of the 
Treatment Phase (Visit 5) and are on a stable dose. Otherwise, melatonin is prohibited from 
5 days prior to the start of Visit 5 to the end of the Follow-Up Visit or Early Termination 
Visit. 
If subjects participated in a previous study with KP415 (including Study KP415.E01), they 
are allowed to take any medications (including ADHD medications) after completing the 
previous study with KP415 and before starting the current study, except for the medications 
and the time intervals specified in this protocol. 
10.2. Medication Restrictions for New Subjects 
• Stimulant ADHD medications (with the exception of study drug), including herbal 
medications, are prohibited from 5 days prior to the start of the Dose Optimization Phase 
(Visit 2) to the end of the Follow-Up Visit or Early Termination Visit. These include: 
methylphenidate, amphetamine, Ritalin®, Ritalin® SR, Metadate® ER, Concerta®, 
dextromethylphenidate, Focalin®, dextroamphetamine, Dexedrine®, Adderall®. 


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• Non-Stimulant ADHD medications are prohibited from 14 days prior to the start of the Dose 
Optimization Phase (Visit 2) to the end of the Follow-Up Visit or Early Termination Visit. 
These include: Atomoxetine, guanfacine, clonidine; and SSRIs such as fluoxetine and 
paroxetine. 
• The following medications are prohibited from 14 days prior to the start of the Dose 
Optimization Phase (Visit 2) to the end of the Follow-Up Visit or Early Termination Visit: 
o Tricyclic antidepressants. 
o Monoamine oxidase inhibitors (MAOIs) 
o Mood stabilizers (e.g., lithium, valproate, quetiapine) 
o Antipsychotics (e.g., risperidone, olanzapine) 
o Coumarin anticoagulants 
o Anticonvulsants 
o Halogenated anesthetics 
o Phenylbutazone 
 
• Sedative hypnotics/sleep enhancers (with the exception of melatonin) are prohibited from 
14 days prior to the start of the Dose Optimization Phase (Visit 2) to the end of the Follow-
Up Visit or Early Termination Visit. 
• Melatonin is allowed if subjects have taken it for more than 30 days before the start of the 
Dose Optimization Phase (Visit 2) and are on a stable dose. Otherwise, melatonin is 
prohibited from 5 days prior to Visit 2 to the end of the Follow-Up Visit or Early 
Termination Visit. 
Medications allowed during the course of the study include nasal steroids, bronchodilators, 
acetaminophen and nonsteroidal anti-inflammatory medications; non-sedating antihistamines such 
as cetirizine, loratadine, and fexofenadine; mometasone; and approved courses of prescription and 
nonprescription medications for the treatment of acute illnesses. 
10.3. Birth Control 
Female subjects must agree, when they are of childbearing potential at Screening or when they 
become of childbearing potential during the study to use one of the following forms of birth control 
from screening until 14 days after the last dose of study drug has been taken, unless a different 
timeframe is listed below: 
a. Double barrier (diaphragm with spermicide; condoms with spermicide) 
b. Intrauterine device (IUD) 
c. Total abstinence (must agree to use a double barrier method if they become sexually 


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active between Screening and 14 days after the last dose of study drug). 
d. Implanted or intrauterine hormonal contraceptives in use for at least 3 consecutive 
months prior to Screening. 
e. Oral, patch, or injected contraceptives, or vaginal hormonal device (i.e., NuvaRing®), in 
use for at least 3 consecutive months prior to Screening. 
Male subjects with female partners must agree, when their partners are of childbearing potential at 
Screening or when their partners become of childbearing potential during the study, to remain 
abstinent or agree to use an effective and medically acceptable form of birth control from the time 
of written or verbal assent to at least 14 days after the last dose of study drug has been taken. 
“Of childbearing potential” is defined in Section 12.9. 
11. INVESTIGATIONAL PRODUCT 
11.1. Active Pharmaceutical Ingredients 
The chemical name of the KP415 prodrug is 3-(((S)-1-carboxy-2-hydroxyethyl)carbamoyl)-1-
((((R)-2-((R)-2-methoxy-2-oxo-1-phenylethyl)piperidine-1-carbonyl)oxy)methyl)pyridine-1-ium 
chloride. It is a single d-methylphenidate molecule covalently attached via a carbamate bond to a 
methylene oxide linker which in turn is connected to the nitrogen of the pyridine ring of a 
nicotinoyl-serine moiety. 
11.2. Clinical Trial Material 
The capsules of study drug (KP415 capsules) with contain two active pharmaceutical ingredients: 
d-methylphenidate hydrochloride as the immediate release (IR) d-methylphenidate component, and 
KP415 prodrug as the extended release (ER) d-methylphenidate component. In terms of d-MPH 
equivalent amounts, all capsule strengths contain 30% of d-MPH (IR component) and 70% of d-
MPH from the KP415 prodrug. The total equivalent amount of d-methylphenidate (d-MPH) in each 
capsule strength (used as daily doses in this study), and the amounts of both APIs are listed in the 
following table. 
Total 
d-MPH 
dose 1 
(mg) 
d-MPH 2 
 
 
(mg) 
KP415 
Prodrug 3 
 
(mg) 
20 
6 
28 (14) 
30 
9 
42 (21) 
40 
12 
56 (28) 
1. Based on the d-MPH amount plus the equivalent amount of d-MPH as KP415 prodrug. 
2. The dose of d-MPH is expressed in terms of d-methylphenidate hydrochloride. 
3. The dose of KP415 prodrug is expressed in terms of KP415 chloride. The amount of d-MPH hydrochloride 
equimolar to each KP415 prodrug dose is listed between parentheses. 


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The KP415 prodrug is not yet a scheduled controlled substance; however, methylphenidate is a 
Schedule II substance under the Controlled Substances Act. As a result of the d-MPH content in the 
KP415 capsules, the drug product used in this study is a Schedule II product. Therefore, study sites 
are required to have the appropriate permit from the Drug Enforcement Agency (DEA) to receive, 
store, ship and dispense the KP415 product according to all local, state, and federal regulations for 
Schedule II substances. 
Unblinded capsules with 20, 30, and 40 mg KP415 product will be used in the study. All study drug 
will be supplied by the Sponsor (or designee). The Sponsor (or designee) will supply sufficient 
quantities of KP415 to allow for completion of the study. The study drug shipment(s) will be 
shipped to each site after site activation (i.e., after all required regulatory documentation has been 
received by the Sponsor or designee and a contract has been executed). The lot numbers of study 
drug supplied will be recorded in the study report. 
All other drug products needed for the conduct of the study (such as allowed medications to treat 
Adverse Events, including acetaminophen and nonsteroidal anti-inflammatory medications) will be 
commercially available products obtained by each research site. 
11.3. Pharmaceutical Formulation 
KP415 will be provided in size 3 capsules consisting of a color-coded (by strength) hydroxypropyl 
methylcellulose (HPMC) capsule shell with text indicating the name (KP415) and the strength 
(either 20 mg, 30 mg or 40 mg). Besides KP415 drug substance, each capsule of study drug contains 
the following inactive ingredients: microcrystalline cellulose, crospovidone, colloidal silicon 
dioxide, and magnesium stearate. 
11.4. Packaging and Labeling 
The KP415 capsules will be packaged and labeled appropriately, according to the appropriate FDA 
regulations. 
11.4.1. Dose Optimization Phase 
Unblinded KP415 capsules will be dispensed to the subjects as bottles with 10 capsules. One bottle 
contains enough drug supply for one subject, for at least 7 days of dosing in the Dose Optimization 
Phase (1 capsule/day) and 3 extra capsules to cover the potential loss of capsules or extra dosing 
days before the next visit. Each bottle will be dispensed with instructions on how to administer 
study drug. 


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11.4.2. Treatment Phase 
Unblinded KP415 capsules will be dispensed to the subjects as bottles with 35 capsules. One bottle 
contains enough drug supply for one subject, for at least 30 days of dosing in the Treatment Phase 
(1 capsule/day) and 5 extra capsules to cover the potential loss of capsules or extra dosing days 
before the next visit. Each bottle will be dispensed with instructions on how to administer study 
drug. 
11.5. Dispensing and Drug Return Procedures 
11.5.1. General Dispensing and Drug Return Procedures 
Unblinded bottles of drug supply (KP415 capsules) will be dispensed at each visit of the study with 
enough capsules for treatment until the next visit. The assigned study drug will consist of one of the 
following: 20, 30 or 40 mg KP415 capsules. 
At each visit, a bottle will be dispensed to the subject’s parent or guardian with instructions when 
and how to administer study drug while at home, under supervision of parent or legal guardian. At 
the day of each visit, subjects may take their dose of study drug at home before coming to the study 
site or subjects will be administered study drug at the study site. Subjects will be instructed to take 
study drug every morning while at home under the supervision of their parent/legal 
guardian/caregiver. The capsule needs to be swallowed whole, or may be taken by sprinkling the 
contents of the capsule over a small amount of applesauce, or putting the contents in a small amount 
of water. See Appendix A for detailed instructions. 
At each visit, subjects will return to the study site with unused study drug, and site personnel will 
record the number of returned and administered capsules of unblinded study drug for drug 
accountability and compliance. 
In the event that subjects report lost study drug during the at-home dosing periods, they will be 
instructed to contact the study site as soon as possible after the loss. Lost drug supply may be 
replaced with the appropriate new bottle. 
The Investigator will not supply study drug to anyone other than those named as sub-investigators 
on FDA Form 1572, designated site staff, and subjects in the study. 
11.5.2. Dispensing in Dose Optimization Phase (Visit 2, 3, and 4) 
Unblinded bottles of drug supply will be dispensed at each visit as follows: 
• Visit 2: Subjects will be dispensed an unblinded bottle with 10 capsules of 30 mg KP415 
product (starting dose for Dose Optimization). 


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• Visit 3: Subjects will return to the research clinic after 7 ±3 days for Visit 3 with unused 
study drug, and will be dispensed either a bottle with 30 mg KP415 capsules (same daily 
dose as Week 1), with 20 mg KP415 capsules (dose level decrease from Week 1), or with 
40 mg KP415 capsules (dose level increase from Week 1). 
• Visit 4: Subjects will return to the research clinic after 7 ±3 days for Visit 4 with unused 
study drug, and will be dispensed either a bottle with 20, 30 or 40 mg KP415 capsules (same 
daily dose as Week 2, or either a dose level decrease or increase from Week 2). 
11.5.3. Dispensing in Treatment Phase (Visits 5 to 16) 
Unblinded bottles of drug supply will be dispensed at each visit as follows: 
• Visit 5: Subjects will be dispensed an unblinded bottle with 35 capsules of the optimized 
dose of KP415 (either 20 mg, 30 mg or 40 mg capsules). For rolled-over subjects from Study 
KP415.E01, the optimized dose as determined in Study KP415.E01 will be used. For new 
subjects, the optimized dose will be determined at the end of the Dose Optimization Phase 
in the current study. 
• Visit 6 to Visit 16: Subjects will return to the research clinic with unused study drug, and 
will be dispensed a new bottle with 35 capsules of either 20 mg, 30 mg or 40 mg KP415 
product. Since the Investigator may increase or decrease the dose of KP415 during the 
Treatment Phase, based on individual tolerability and dose response, the capsule strengths 
dispensed at Visit 6 to Visit 16 may be different from the previous visit. 
11.5.4. Dispensing at Unscheduled Visits 
At unscheduled visits (see Section 9.5), if needed, the Investigator may decide to change the daily 
KP415 dose. In this case, a new bottle with capsules of either 20 mg, 30 mg or 40 mg KP415 product 
will be dispensed to the subjects, and unused study drug previously dispensed will need to be 
returned. The same dispensing and drug return procedures (see Section 11.5.1) will be followed as 
for scheduled visits. 
11.6. Storage of Study Drug 
Study drug will be stored at controlled room temperature 20°-25°C (68°-77°F) with excursions 
allowed between 15° and 30°C (59° and 86°F). Transient spikes up to 40°C are permitted as long 
as they do not last for more than 24 hours. Study drug will be stored at the study site in a safe, secure 
area with limited, controlled access for Schedule II substances in accordance with all local, state, 
and federal regulations. Investigational products must not be frozen. The Investigator will ensure 
that adequate precautions are taken, including storage of the study drug in a securely locked, 
substantially constructed cabinet, or other securely locked, substantially constructed enclosure, 
access to which is limited, to prevent theft or diversion of the substance into illegal channels of 


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distribution. 
The investigational product(s) must be stored as indicated. Deviations from the storage 
requirements, including any actions taken, must be documented and reported to the Sponsor. Once 
a deviation is identified, the investigational product must be quarantined and not used until the 
Sponsor provides documentation of permission to use the investigational product. 
11.7. Study Drug Accountability 
An accurate and current accounting of the dispensing and return of study drug for each subject, in 
both the Dose Optimization Phase and the Treatment Phase, will be maintained on an ongoing basis 
by a member of the study site staff. The number of study drug dispensed will be recorded on the 
Investigational Drug Accountability Record. The study monitor will verify these documents 
throughout the course of the study. 
12. SAFETY AND EFFICACY ASSESSMENTS 
12.1. Medical History 
A complete medical history will be obtained at the Screening Visit including the recording of 
demographic data (date of birth, sex, age, race, ethnicity), collection of previous surgeries, 
medications and chronic conditions, past or present illnesses or dysfunctions, substance/drug abuse, 
and history of allergies or idiosyncratic responses to drugs. Medical history (changes from 
screening) will be updated at subsequent visits after the Screening Period. 
12.2. Physical Examination 
For all subjects, a complete physical examination will be completed at Screening, after 
approximately 6 months of treatment (Visit 11), after the last dose of study drug (Visit 17, EOT), 
and at Early Termination (if possible). The complete physical examination will include a review of 
the subject’s general appearance, skin, head and neck (eyes, ears, nose, mouth, and throat), lymph 
nodes, thyroid, musculoskeletal/extremities, cardiovascular system, lungs, abdomen and a brief 
examination of the neurological system. 
Body weight, height and BMI will be determined at all visits to follow the growth of the subjects. 
Height will be recorded in centimeters (cm) with the subject’s shoes removed. Body weight will be 
measured in kilograms (kg); subjects will remain in their normal clothing with shoes and jacket 
(and/or outer clothing) removed. 
12.3. ADHD Diagnosis and Severity Assessments 
For new subjects at Screening, eligible subjects must meet the inclusion criteria for a primary 
diagnosis of ADHD by Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition 
(DSM-5) 
criteria 
for 
a 
primary 
diagnosis 
of 
ADHD 
(combined, 
inattentive, 
or 


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hyperactive/impulsive presentation) per clinical evaluation and confirmed by the Mini International 
Neuropsychiatric Interview for Children and Adolescents (MINI-KID). 
Since rolled-over subjects from Study KP415.E01 will need to have that study completed, their 
ADHD diagnosis and diagnosis confirmation was conducted in Study KP415.E01. 
For all subjects, the following scales will be used during the study to globally assess the changes in 
ADHD severity over time: 
• ADHD-Rating Scale-5 (ADHD-RS-5): The ADHD-RS-5 is an 18-item scale (DuPaul 
2016) based on Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-
5) (American Psychiatric Association 2013) criteria of ADHD that rates symptoms on a 4-
point scale. Each item is scored using a combination of severity and frequency ratings 
from a range of 0 (reflecting no symptoms or a frequency of never or rarely) to 3 
(reflecting severe symptoms or a frequency of very often), so that the total ADHD-RS-5 
scores range from 0 to 54. The 18 items can be divided into two 9-item subscales: One for 
hyperactivity/impulsivity and the other for inattentiveness. Scores will be obtained during 
a clinician-directed interview with the parent/guardian/caregiver at each visit in the Dose 
Optimization Phase. 
• Clinical Global Impressions–Severity (CGI-S): The CGI-S is a clinician-rated scale that 
evaluates the severity of psychopathology (ADHD symptoms in the study) on a scale from 
1 (not at all ill) to 7 (among the most severely ill) (Busner and Targum 2007). 
• Clinical Global Impressions–Improvement (CGI-I): The CGI-I is a clinician-rated scale 
that evaluates the improvement of psychopathology (ADHD symptoms in the study) on a 
scale from 1 (very much improved) to 7 (very much worse). 
During the Dose Optimization Phase (new subjects only), the ADHD-RS-5, CGI-I and CGI-S scale 
assessments are the main efficacy variables (in conjunction with tolerability and safety) to guide 
dose optimization. During the Treatment Phase, the ADHD-RS-5 and CGI-S scale assessments are 
the efficacy variables to evaluate the changes in ADHD severity over time, and may be used (in 
conjunction with tolerability and safety) to adjust the dose of study drug. 
12.4. Children’s Sleep Habits Questionnaire (CSHQ) 
The modified, abbreviated Children’s Sleep Habits Questionnaire (CSHQ) will be used to assess 
the sleep behavior during the Treatment Phase. The CSHQ is a retrospective, 33-item parent 
questionnaire to examine sleep behavior in small children (Owens 2000a, Owens 2000b). Items are 
rated on a 3-point scale of “Usually”, “Sometimes” and “Rarely” for occurrences in a number of 
key sleep domains. Scores will be obtained during a clinician-directed interview with the 
parent/guardian/caregiver at the visits in the Dose Optimization Phase for new subjects (Visit 2) 


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and in the Treatment Phase for all subjects (Visit 5 to Visit 17). 
12.5. Columbia-Suicide Severity Rating Scale (C-SSRS) 
Suicidal ideation will be assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS, 
Pediatric Version) (Posner 2010). The “Children’s Baseline/Screening” version will be assessed at 
Screening, and the “Children’s Since Last Visit” version will be assessed at all visits of the Dose 
Optimization Phase (new subjects only), at all of the Treatment Phase visits, and at Follow-Up or 
Early Termination. 
Subjects who, in the opinion of the Investigator, have clinically significant suicidal 
ideation/behavior, based on history of attempted suicide and the C-SSRS assessment at Screening 
or at any time before the last dose of study drug, will be excluded from further participation in the 
study, and further evaluation and/or preventive intervention steps for suicidal behavior will be 
taken, at the discretion of the Investigator. 
12.6. Vital Signs 
Vital sign measurements will be obtained after the subject has been seated for 3 minutes. Vital signs 
will include sitting blood pressure (systolic and diastolic measurements), pulse rate (beats per 
minute), respiratory rate (breaths per minute), and oral temperature. Vital signs will be collected 
once at each visit. At the discretion of the Investigator, in order to ensure accuracy, out-of-range 
vital signs may be repeated once, at least 2 minutes after an abnormal finding. 
12.7. 12-Lead Electrocardiogram 
A 12-lead ECG will be obtained after the subject has been in a supine position for a minimum of 3 
minutes. Abnormal ECGs may be repeated for confirmation in which case only the repeated ECG 
will be recorded. The QT interval corrected for heart rate will be calculated with Fridericia’s 
formula (QTcF). ECGs will be obtained at Screening, after approximately 6 months of treatment 
(Visit 11), after the last dose of study drug (Visit 17, EOT), and at Early Termination (if possible). 
ECG recordings will be evaluated by skilled readers operating from a centralized ECG laboratory. 
12.8. Clinical Laboratory Measurements 
All clinical laboratory samples will be sent to a central laboratory for analysis. Up to approximately 
40 mL of blood will be collected for clinical chemistries, hematology, and pregnancy test (if 
applicable) from each subject during the study. Clinical Laboratory Measurements will be 
performed at Screening, after approximately 6 months of treatment (Visit 11), after the last dose of 
study drug (Visit 17, EOT), and at Early Termination (if possible). Samples for Clinical Laboratory 
Measurements at Screening Visit 1A (new subjects), Visit 11, and Visit 17 (EOT) will be collected 
under fasting conditions. 


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The Clinical Laboratory evaluations will consist of the following: 
• Total Hematology as well as differential and Coagulation: red blood cell count, white 
blood cell count with differential (neutrophils, lymphocytes, monocytes, eosinophils, 
basophils), hemoglobin, hematocrit and platelets, Prothrombin Time (PT) and Partial 
Thromboplastin Time (PTT). 
• Serum Chemistry: aspartate aminotransferase (AST), alanine aminotransferase (ALT), 
albumin, alkaline phosphatase, bicarbonate, total bilirubin, blood urea nitrogen, 
phosphorus (inorganic) calcium, chloride, creatine phosphokinase, creatinine, gamma 
glutamyl transferase, glucose, lactate dehydrogenase, potassium, sodium, total protein, 
thyroid stimulating hormone (TSH), and uric acid. TSH will be measured at Screening 
only, for New Subjects only who did not previously participated in Study KP415.E01 (to 
evaluate the exclusion criterion for uncontrolled thyroid disease). 
• Urinalysis: microanalysis for specific gravity, pH, protein, glucose, ketones, blood, 
nitrites, leukocytes. If positive for blood, protein or nitrites, a microscopic examination 
will be performed. 
• Urine Screen for Alcohol Drugs of Abuse (new subjects only): At Screening (Visit 1), 
urine samples will be tested for alcohol and drugs of abuse (amphetamines, 
methamphetamines, benzodiazepines, barbiturates, cannabinoids, cocaine, opioids 
including oxycodone). If the urine test is positive for alcohol and drugs of abuse at 
Screening, the subject will be excluded from study participation, with the exception of the 
following: Depending on a subject's current ADHD medication at Screening, the urine 
screen at Screening may test positive for ADHD medications such as amphetamines and 
methamphetamines. 
• Urine Screen for Methylphenidate: At Screening (Visit 1A, new subjects only), Visit 2 
(new subjects only) and Visit 5 (roll-over subjects only), urine samples will be tested for 
methylphenidate. A urine dipstick (e.g., NarcoCheck®) will be used to screen for the 
presence of methylphenidate in the urine. If a subject's current ADHD medication at 
Screening (Visit 1A, new subjects) contains MPH, the urine screen at Screening may test 
positive for MPH. 
12.9. Pregnancy Test 
Pregnancy Tests will be performed for all female subjects of childbearing potential. A serum β-
hCG pregnancy test will be performed at Screening. A urine pregnancy test will be performed at 
Visits 2 (new subjects), at Visit 5 to Visit 17, and at Follow-Up or Early Termination. A positive 
pregnancy test before the last dose of study drug will exclude a subject from further participation 
in the study. A positive urine pregnancy test will be confirmed with a serum β-hCG pregnancy test. 


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Childbearing potential is defined as follows: Girls under the age of 12 who have not had their first 
period will be considered “not of child-bearing potential”. Girls of 12 years and older (including 
girls who will become 12 years or older during the study) will be considered “of child-bearing 
potential”, even if they have not yet had their first period. Irrespective of age, girls who have had 
their first period, will be considered “of child-bearing potential”. 
12.10. Adverse Event Assessments 
Adverse Events will be assessed and recorded from the first day of study drug administration 
through either Follow-Up or Early Termination. While subjects are at the research clinic after 
administration of study drug, AEs will be monitored continuously by study staff. During 
administration of study drug away from the research clinic, subject’s parent/guardian will be 
instructed to contact the study site for the reporting of AEs during the dosing period at home. In 
addition, study staff will inquire parent/guardian during the next study visit about AEs during the 
dosing period at home. Definitions and details of AE reporting and documentation are listed in 
Section 16. In cases in which the occurrence of an AE to the subject is unclear or for safety-related 
medical questions, the Medical Monitor should be consulted (for contact information, see Page 2). 
13. DISCONTINUATION AND REPLACEMENT OF SUBJECTS 
13.1. Withdrawal of Subjects from the Study 
A subject may be discontinued or choose to withdraw from study treatment at any time if the subject, 
the Investigator, or the Sponsor feels that it is not in the subject’s best interest to continue. The 
following is a list of possible reasons for study treatment discontinuation: 
• 
Subject withdrawal of consent. 
• 
Subject is not compliant with study procedures. 
• 
Adverse event that in the opinion of the Investigator would be in the best interest of the 
subject to discontinue study treatment. 
• 
Lack of efficacy 
• 
Protocol violation requiring discontinuation of study treatment. 
• 
Lost to follow-up when there is no response to two attempts by phone and a registered 
letter to the subject. After these 3 failed attempts, the subject will be considered lost to 
follow-up. 
• 
Sponsor request for early termination of the study. 
• 
Positive pregnancy test (tested in females of childbearing potential) before the last dose 
of study drug. 
• 
Out-of-range vital signs, at the discretion of the Investigator. In order to ensure accuracy, 
out-of-range vital signs may be repeated once, at least 2 minutes after an abnormal 
finding. 
• 
For other reasons (e.g., significant protocol violation, non-compliance, overdose). 
 
If a subject is withdrawn from treatment due to an adverse event, the subject will be followed and 


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treated by the Investigator until the abnormal parameter or symptom has resolved or stabilized. 
All subjects are free to withdraw from participation at any time, for any reason, specified or 
unspecified, and without prejudice. 
If a subject meets withdrawal criteria during the Dose Optimization Phase or the Treatment Phase, 
the subject will be withdrawn, and Early Termination procedures will be completed. 
At the discretion of the Investigator, ensuring the safety of the subjects, any ET procedures that 
were already performed on the same day as part of the procedures of the Dose Optimization Phase 
or the Treatment Phase do not need to be repeated. 
13.2. Replacement of Subjects  
Subjects who withdraw from the study during the Treatment Phase will not be replaced. Subjects 
who withdraw from the study during the Dose Optimization Phase may be replaced. 
14. STUDY ENDPOINTS 
This study is primarily a safety study in the target patient population after at least 6 months of daily 
oral doses of KP415 capsules. Therefore, the primary endpoint is the safety. 
14.1. Safety Endpoints 
• The occurrence of Treatment-Emergent Adverse Events (TEAEs) will be assessed starting 
following the first dose of study drug, and ending with the Follow-Up Visit or Early 
Termination Visit. 
• Physical examinations will be performed at the first visit (at Screening, before the first dose 
of study drug), after approximately 6 months of treatment (Visit 11), and at the end of the 
Treatment Phase (Visit 17, EOT) or at Early Termination. 
• Clinical laboratory tests will be performed at the first visit (at Screening, before the first 
dose of study drug), after approximately 6 months of treatment (Visit 11), and at the end of 
the Treatment Phase (Visit 17, EOT) or at Early Termination. 
• ECG parameters will be collected at the first visit (at Screening, before the first dose of 
study drug), after approximately 6 months of treatment (Visit 11), and at the end of the 
Treatment Phase (Visit 17, EOT) or at Early Termination. 
• Vital signs, height, weight, and BMI will be collected at each visit. 
• A C-SSRS will be performed at each study visit. 


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14.2. Efficacy Endpoints 
During the Dose Optimization Phase (new subjects only): 
• 
CGI-S will be assessed at each visit (Screening to Visit 5). ADHD-RS-5 will be 
administered at Visits 2 through Visit 5. CGI-I will be assessed at Visits 3, 4, and 5 
(since CGI-I is an ADHD improvement assessment, it will not be assessed at Screening 
and at Visit 2). 
During the Treatment Phase (all subjects): 
• 
ADHD-RS-5 and CGI-S will be assessed at each visit (Visit 5 to Visit 17, EOT). 
14.3. Sleep Behavior Endpoint 
The modified, abbreviated Children’s Sleep Habits Questionnaire (CSHQ) will be used to assess 
the sleep behavior in the Dose Optimization Phase for new subjects (Visit 2) and in the Treatment 
Phase for all subjects (Visit 5 to Visit 17). The baseline will be measured before the first dose of 
study drug, at Visit 2 for new subjects and at Visit 5 for roll-over subjects. 
15. STATISTICAL CONSIDERATIONS 
This section summarizes the statistical considerations for this protocol. Details will be provided in 
the Statistical Analysis Plan (SAP) prior to the primary endpoint database lock of the trial. 
15.1. Sample Size Calculation 
No formal sample size calculations were conducted. It was determined that approximately 200 
subjects are adequate to satisfy the primary objective of the study, which is to determine the safety 
and tolerability of KP415 in treating children with ADHD for at least 6 months. Assuming a 
maximum dropout rate of 20% over 6 months, approximately 250 subjects will be enrolled. 
15.2. Populations for Analysis 
Data will be analyzed in this study in the following analysis populations: 
• Treatment-Phase Safety Population: All enrolled subjects in the Treatment Phase who 
received at least one dose of study medication in the Treatment Phase and had at least one post-
dose safety assessment in the Treatment Phase. 
• Efficacy Population: All enrolled subjects who received at least 30 days of study medication 
in the Treatment Phase, who had adequate data to assess the change from baseline of the efficacy 
parameters and who had no protocol deviations that could affect the efficacy parameters. 


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• Dose-Optimization Safety Population: All enrolled subjects in the Dose Optimization Phase 
(“New Subjects”) who received at least one dose of study medication in the Dose Optimization 
Phase and had at least one post-dose safety assessment in the Dose Optimization Phase. 
15.3. Statistical Analyses 
15.3.1. General Approach 
The primary focus of the statistical analyses are the safety assessments during the Treatment Phase. 
The secondary focus of the statistical analyses is the efficacy during the Treatment Phase. The safety 
and efficacy parameters during the Dose Optimization Phase (for new subjects only) will be 
summarized descriptively. The efficacy results will be judged with caution since this study is open 
label and has no control group. 
Analysis Populations: All baseline analyses will be performed using the Treatment-Phase Safety 
Population. The primary safety analysis (during the Treatment Phase) will be performed using the 
Treatment-Phase Safety Population. The efficacy analyses and sleep behavior (CSHQ) across the 
Treatment Phase will use the Efficacy Population. Data from the Dose Optimization Phase (Dose-
Optimization Safety Population) will be summarized descriptively. 
Descriptive Statistics: For descriptive statistics, the following will be reported: 
• Continuous data: n, mean, standard deviation, coefficient of variation (CV%), median, 
minimum and maximum. 
• Categorical data: n/N, percentage of total per arm and 95% confidence interval per 
category. 
 
15.3.2. Attrition 
The number of subjects enrolled and the number of subjects remaining in the study by month will 
be reported. The number of subjects who withdraw early from the study will be tabulated with the 
reason for early withdrawal. The main reasons overall for early withdrawal will be determined. For 
each main reason for early withdrawal, an assessment will be made when in the course of treatment 
most subjects withdrew early. Baseline variables and dose of study drug will be compared between 
subjects who withdrew early and subjects who completed the study. 
15.3.3. Drug Exposure and Dosing Pattern 
The mean daily dose of KP415 (mg), the mean daily dose of KP415 by body weight (mg/kg), and 
the mean daily dose of KP415 by body surface area (mg/m2) will be calculated by month, and will 
be compared over time (percent change from starting dose in the Treatment Phase) to explore dose 
changes over the course of the study. The number of subjects who did not take study drug for any 
continuous period of ≥7, ≥14, ≥21, and ≥28 days in the Treatment Phase will be counted and 


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reported. 
15.3.4. Primary Endpoint Analysis (Safety in the Treatment Phase) 
The primary safety analysis will be conducted on the Treatment-Phase Safety Population. The 
safety assessment will be based on adverse events, physical examinations, vital signs, height, 
weight, and BMI, ECG parameters, clinical laboratory tests and C-SSRS scores. The baseline for 
the safety parameters will be measured at Visit 1A and 1B. 
Adverse events will be coded in accordance with the Medical Dictionary for Regulatory Activities 
(MedDRA). Adverse events with new onset during the study between the initiation of study drug 
and 5 days after the last dose of study drug will be considered treatment-emergent (TEAEs). This 
will include any AE with onset prior to initiation of study drug and increased severity after the 
treatment initiation. 
TEAEs will be summarized by system organ class and preferred term, overall and by average dose. 
This will include overall incidence rates (regardless of severity and relationship to study drug) and 
incidence rates for moderate or severe adverse events. A summary of serious adverse events and 
adverse events leading to early discontinuation from the study will be summarized by average dose. 
Safety laboratory tests and vital signs will be summarized by post-treatment change from baseline 
for each of the parameters using descriptive statistics overall and by average dose. Those subjects 
with significant laboratory abnormalities will be identified in data listings. Additional safety 
parameters will be summarized in data listings. See Section 16 for more information on safety data. 
15.3.5. Secondary Endpoint Analyses (Efficacy and CSHQ in the Treatment Phase) 
Changes in ADHD-RS-5, CGI-S and CSHQ will be analyzed in the Efficacy Population. The 
baseline for ADHD-RS-5, CGI-S and CSHQ will be measured at Visit 5 for roll-over subjects and 
at Visit 2 for new subjects. 
15.3.6. Descriptive Analyses (Safety and Efficacy in the Dose Optimization Phase) 
For new subjects only, the safety and efficacy parameters during the Dose Optimization Phase 
(Dose-Optimization Safety Population, from Screening to Visit 5) will be summarized 
descriptively. The baseline will be measured at Screening or at Visit 2 (before the first dose in the 
Dose Optimization Phase). 
15.3.7. Abuse Potential Safety Analyses 
In accordance with the 2017 FDA Guidance for Industry, Assessment of Abuse Potential of Drugs, 
the following analyses will be performed in the Treatment Phase: 


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• Systematic categorization and tabulation of AEs that are abuse potential-related, using the 
MedDRA Preferred Terms, including euphoria-related terms, terms of altered attention, 
cognition and mood, and dissociative/psychotic terms (FDA Guidance 2017, Sellers and 
Romach 2017). An analysis by dose, age, and gender; and by case, in order to understand 
the incident that led to the AEs, establish the time at which AEs appear following drug 
administration, the duration of the AEs, and which AEs overlap temporally. 
• Analysis of subject’s study drug accountability assessments that may provide information 
about the incidence of signals suggestive of abuse, such as substance use disorders, 
overdose, drug diversion or drug loss. 
15.3.8. Baseline Descriptive Statistics 
The key baseline characteristics (see the Statistical Analysis Plan (SAP) for list of baseline 
characteristics) will summarized descriptively. 
15.3.9. Planned Interim Analysis 
An interim analysis of the safety data will be conducted after approximately all subjects remaining 
in the study have completed 180 days (approximately 6 months) of treatment (Visit 11). The focus 
of the interim analysis are the safety assessments (primary endpoints, See Section 15.3.5) during 
the first 6 months of treatment in the Treatment Phase. The safety data will be analyzed with the 
same statistical methods as planned for the main analysis after completion of the study. The results 
from the interim safety analysis will be used to determine whether the study can be stopped (see 
Section 8.6 for the stopping rules). All other endpoints (including the secondary endpoints) and 
assessments will also be analyzed as part of the interim analysis. 
15.3.10. 
Subgroup Analyses 
Subgroup analyses will include safety, efficacy and CSHQ endpoints by study site, dose (including 
cumulative dose), duration of treatment, previous stimulant exposure, age, gender, and race. 
Subgroup analyses will focus on the Treatment Phase. Subgroup analyses will be described in the 
SAP. 
15.3.11. 
Tabulation of Individual Participant Data 
All data will be listed. Listings will be sorted in the following order: treatment, subject ID, parameter 
(where applicable), and visit (where applicable). For TEAEs, a listing with date and type of each 
subject’s TEAE will be provided. Details will be outlined in the SAP. 
15.3.12. 
Exploratory Analyses 
Exploratory analyses will be described in the SAP. 


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16. ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION 
16.1. Adverse Events 
16.1.1. Recording and Monitoring of Adverse Events 
For the purpose of this clinical trial, all Adverse Events will be recorded and monitored for all 
enrolled subjects from the moment they receive the dose of study drug until they complete the study 
at the EOS (the Follow-Up visit or the Early Termination Visit). 
16.1.2. Definition 
An adverse event (AE) is any untoward medical occurrence in a clinical investigation of a patient 
administered a pharmaceutical product and that does not necessarily have a causal relationship with 
the treatment. An AE is therefore any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom or disease temporally associated with the administration of an 
investigational product, whether or not related to that investigational product. An unexpected AE is 
one of a type not identified in nature, severity, or frequency in the current Investigator’s Brochure 
or of greater severity or frequency than expected based on the information in the Investigator’s 
Brochure. 
The Investigator will probe, via discussion with the subject, for the occurrence of AEs during each 
subject visit and record the information in the site’s source documents. Adverse events will be 
recorded in the patient eCRF. Adverse events will be described by duration (start and stop dates and 
times), severity, outcome, treatment and relation to study drug, or if unrelated, the cause. 
16.1.3. AE Grading  
Adverse Events shall be graded with regard to severity according to criteria defined in the Common 
Terminology Criteria for Adverse Events v4.0 (CTCAE). Grade refers to the severity of the AE. 
The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE 
based on this general guideline. 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental Activity of Daily Living (ADL). 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 


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Grade 5 
Death related to AE. 
16.1.4. AE Relationship to Study Drug 
The relationship of an AE to the study drug should be assessed using the following: 
1. Definitely - Previously known toxicity of agent; or an event that follows a reasonable 
temporal sequence from administration of the drug; that follows a known or expected 
response pattern to the suspected drug; that is confirmed by stopping or reducing the dosage 
of the drug; and that is not explained by any other reasonable hypothesis. 
2. Probably - An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to the suspected drug; that is 
confirmed by stopping or reducing the dosage of the drug; and that is unlikely to be 
explained by the known characteristics of the subject’s clinical state or by other 
interventions. 
3. Possibly - An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to that suspected drug; but that 
could readily have been produced by a number of other factors. 
4. Unrelated - An event that can be determined with certainty to have no relationship to the 
study drug. 
16.2. Serious Adverse Events 
A Serious Adverse Event (SAE) is defined as any AE occurring at any dose that results in any of 
the following outcomes: 
• Death 
• A life-threatening adverse experience 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant disability/incapacity 
• A congenital anomaly/birth defect 
• Other important medical events may also be considered an SAE when, based on 
appropriate medical judgment, they jeopardize the subject or require intervention 
to prevent one of the outcomes listed. 
 
Note that AEs of Grade 3 due to hospitalization or prolongation of a hospitalization, and Grade 4 
and Grade 5 per CTCAE grading criteria are classified as SAEs. 
16.2.1. Serious Adverse Event Reporting 
Within 24 hours after a SAE detection, observation, or report of occurrence (regardless of the 


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relationship to test article), the investigator/qualified designee will complete a paper 
SAE/Overdosage report form with required information regarding the SAE and submit the 
completed form to Premier Research Pharmacovigilance. The data will also be entered into the 
appropriate module of the EDC as soon as possible after the paper form is sent to Premier Research 
Pharmacovigilance. 
The site is to report SAEs in the EDC and at the same time report via SAE report paper form to 
the below contact info: 
 
Premier Research Pharmacovigilance email address: 
GlobalPV-US@premier-research.com 
Fax Number: 215-972-8765 
 
These SAE reports must contain the following information: 
1. Study name/number 
2. Study Drug 
3. Investigator details (name, phone, fax, e-mail) 
4. Subject Number 
5. Subject Demographics 
6. Clinical Event 
7. Description 
a. Date of onset 
b. Treatment (drug, dose, dosage form) 
c. AE Relationship to study drug 
d. Action taken regarding study drug in direct relationship to the 
AE 
e. Criteria for “Serious” applicable to the AE 
8. Cause of death (whether or not the death was related to study drug) 
9. Autopsy findings (if available) 
 
Any SAE that occurs during the study should be recorded by each clinical site, and reported to the 
Sponsor or designee. 
SAEs considered definitely, probably, or possibly related to study drug shall also be classified by 
Sponsor as being “expected” or “unexpected.” An unexpected event is one that is not listed in the 
investigator’s brochure (KP415). 
The person responsible for the study shall ensure the study has been carried out in accordance with 
local pharmacovigilance regulations. 
All serious events reporting by Sponsor will adhere to 21 CFR 312.32 for IND drugs (7-day or 15-
day alerts). Unexpected fatal or life-threatening SAEs considered related to the study drug should 
be reported to the FDA by Sponsor with an IND Safety report within 7 days. The Institutional 
Review Board (IRB) will be notified of the alert reports per FDA regulations. 


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16.3. Adverse Event Treatment and Follow-Up 
All AEs, including SAEs, will be followed to resolution when possible. All AEs and treatment 
administered will be recorded on the electronic Case Report Form (eCRF). Treatment may be 
rendered on site under the direction of the Investigator as appropriate. Events requiring diagnostic 
evaluation or treatment beyond the scope of what is available and appropriate within the clinical 
research unit shall be referred in a timely basis to other care providers. Records of diagnostic and 
therapeutic interventions shall be requested in compliance with HIPAA requirements, and those 
received shall be retained in the subject’s file. 
For SAEs that occur during the study, the assessment, treatment, and follow up shall be performed 
for up to at least 30 days after last dose for events considered definitely, probably, or possibly related 
to study drug, and continued until resolved or clinically stable. 
16.4. Overdosage 
For the purposes of this clinical trial, overdosage is defined as the administration of a 
supratherapeutic dose, a daily dose of study drug larger than the highest dose used in the study, i.e., 
>40 mg KP415 product. Within 24 hours after overdosage detection the Investigator or designee 
will complete a paper SAE/Overdosage report form and submit it to Premier Research 
Pharmacovigilance (see contact information in Section 16.2.1). Premier Research will notify the 
sponsor before the end of the next business day after receipt of notification from the site. If the 
overdosage has an associated AE or SAE, the site is to report and document the event as listed in 
this protocol (see Section 16.1 for AEs, and Section 16.2 for SAEs). 
Known signs and symptoms after acute overdosage of d-MPH, resulting principally from 
overstimulation of the central nervous system and from excessive sympathomimetic effects, include 
vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by 
coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, 
tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, and dryness of mucous 
membranes (Concerta® Extended Release Package Insert 2008, Focalin® Package Insert 2017, 
Focalin® XR Package Insert 2015, Ritalin® and Ritalin-SR® Package Insert 2015). Rhabdomyolysis 
has also been reported (Ritalin® and Ritalin-SR® Package Insert 2015). 
Notifications of known incidences of subjects taking more than one capsule of study drug per day 
(irrespective of the dose size), which is considered misuse, will be provided by each study site to 
the Sponsor or designee. 
17. PREGNANCY 
If applicable (see Section 13.1), females with a positive pregnancy test will terminate the study 
early. Within 24 hours of becoming aware of pregnancy, the Investigator or designee will complete 
a paper pregnancy data collection form to be provided to Premier Research (see contact information 


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in Section 16.2.1). Additionally, the Investigator or designee will provide the paper pregnancy data 
collection form to the IRB within a time frame after the incident identification as required by the 
IRB. Premier Research will notify the sponsor before the end of the next business day after receipt 
of notification from the site. 
The pregnancy must be followed up until completion of the pregnancy in order to determine the fetal 
outcome. Any birth defects will be reported as SAEs. Every infant must be followed for 2 months after 
delivery. 
Pregnancy will not be considered an AE or SAE; any pregnancy complication or termination of a 
pregnancy for medical reasons will be recorded as an AE or SAE. The site is to report and document 
AEs and SAEs as listed in this protocol (see Section 16.1 for AEs, and Section 16.2 for SAEs). 
18. PROTOCOL VIOLATIONS 
A protocol violation occurs when the subject, Investigator, or Sponsor fails to adhere to significant 
protocol requirements that materially (a) reduces the quality or completeness of the data, (b) makes 
the Informed Consent Form inaccurate, or (c) impacts a subject's safety, rights, or welfare. 
Examples of protocol violations may include the following: 
1. Inadequate or delinquent Informed Consent 
2. Inclusion/exclusion criteria not met 
3. Unreported serious adverse events 
4. Multiple visits missed or outside permissible windows 
5. Materially inadequate record keeping 
6. Intentional deviation from protocol, Good Clinical Practice, or regulations by study 
personnel 
7. Subject repeated non-compliance with study requirements 
 
It is the Investigator’s responsibility to report to the IRB of any Protocol Violation(s) according to 
the IRBs policy. Copy of the IRB submission will be filed in the site’s regulatory binder and in the 
Sponsor’s files. 
19. DATA MANAGEMENT AND RECORD KEEPING 
19.1. Data Management 
Data will be recorded at the site on eCRFs. All entries on a eCRF are ultimately the responsibility 
of the Site Investigator, who is expected to review each form for completeness, accuracy and 
legibility before signing. All forms must be filled out by using black ink. Errors should be lined out 
but not obliterated and the correction inserted, initialed and dated. An eCRF must be completed for 
each participant for whom parental permission was obtained and who has given written or verbal 
assent. The eCRFs and source documents must be made available to the Sponsor and/or its 
representatives. 


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19.2. Record Keeping 
The Investigators must maintain all documents and records, originals or certified copies of original 
records, relating to the conduct of this trial, and necessary for the evaluation and reconstruction of 
the clinical trial. This documentation includes, but is not limited to, protocol, eCRFs, AE reports, 
subject source data (including records of subjects, subject visit logs, clinical observations and 
findings), correspondence with health authorities and IRB, consent forms, inventory of study 
product, Investigator’s curriculum vitae, and monitor visit logs.  
The Investigators should maintain the trial documents as required by the applicable regulations, and 
should take measures to prevent accidental or premature destruction of documents. Clinical trial 
documents must be kept at the clinical site until written authorization is obtained from the Sponsor. 
19.3. Access to Source Data/Documents 
The Investigators agree that the Sponsor, their representatives, the IRB, and representatives from 
worldwide regulatory agencies will have the right, both during and after the clinical trial, to review 
and inspect pertinent medical records related to the clinical trial. 
20. QUALITY CONTROL AND QUALITY ASSURANCE 
By signing the protocol, the Institution and the Sponsor agree to be responsible for implementing 
and maintaining quality control and quality assurance systems with written standard operating 
procedures to ensure that trials are conducted, and data are generated, documented, and reported in 
compliance with the protocol, accepted standards of Good Clinical Practice. (GCP), ICH and other 
applicable regulations. 
21. ETHICS AND GOOD CLINICAL PRACTICE COMPLIANCE 
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting trials that involve human subjects. Compliance with this 
standard provides public assurance that the rights, safety, and wellbeing of trial subjects are 
protected, consistent with the principles that have their origin in the Declaration of Helsinki, and 
that the clinical trial data are credible. In this study, the 2008 version of the Declaration of Helsinki 
will be adhered to. It can be found on the website of The World Medical Association: 
http://www.wma.net/en/30publications/10policies/b3/17c.pdf 
22. INSURANCE 
The Sponsor certifies that it has taken out a liability insurance policy covering all clinical trials 
under its sponsorship. This insurance policy is in accordance with local laws and requirements. The 
insurance of the Sponsor does not relieve the Site Investigators and the other collaborators from 
maintaining their own liability insurance policy. An insurance certificate will be provided to the 


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IRB according to regulatory requirements. 
23. COMPLETION OF STUDY 
The end of the study will be determined by the stopping rules of the study (see Section 8.6). The 
IRB will be notified about the end of the study according to regulatory requirements. 
24. STUDY ADMINISTRATIVE INFORMATION 
24.1. Protocol Amendments 
Any amendments to the study protocol considered to be a substantial amendment will be 
communicated to the Investigator by the Sponsor. All substantial protocol amendments will 
undergo the same review and approval process as the original protocol and may be implemented 
after it has been approved by the IRB, unless immediate implementation of the change is necessary 
for subject safety. In this case, the situation must be documented and reported to the IRB according 
to all relevant regulatory requirements. 
A protocol amendment is considered to be a substantial amendment if it is likely to affect the safety, 
physical, or mental integrity of subjects in the study; the scientific value of the study; the conduct 
or management of the study; or the quality or safety of any Investigational Medicinal Product used 
in the study. 
Any other minor changes to the protocol not considered to be substantial amendments will not need 
prior approval of the IRB and will be communicated to the Investigator by the Sponsor. 
 
 


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25. REFERENCES 
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth 
Edition (DSM-5). Arlington, VA, American Psychiatric Association, 2013. 
Busner J, Targum SD. The Clinical Global Impressions Scale: Applying a research tool in 
clinical practice. Psychiatry 4:28–37, 2007. 
Challman TD, Lipsky JJ. Methylphenidate: its pharmacology and uses (2000). Mayo Clin Proc. 
75(7):711-21. 
Concerta® Extended Release [Package Insert]. Janssen Pharmaceuticals, Inc. 2008. 
DuPaul GJ, Power TJ, Anastopoulos AD, Reid R: ADHD Rating Scale-5 for Children and 
Adolescents: Checklists, Norms, and Clinical Interpretation. New York: Guildford, 2016. 
Focalin® [Package Insert]. Novartis Pharmaceuticals Corporation. 2017. 
Focalin® XR [Package Insert]. Novartis Pharmaceuticals Corporation. 2015. 
Food and Drug Administration, Assessment of Abuse Potential of Drugs. (2017, January). Guidance 
for Industry, U.S. Department of Health and Human Services, Center for Drug Evaluation and 
Research, Washington, DC. 
Leonard BE, McCartan D, White J, King DJ. Methylphenidate: a review of its 
neuropharmacological, neuropsychological and adverse clinical effects. Hum Psychopharmacol. 
19:151-80, 2004. 
Morton WA, Stockton GG. Methylphenidate Abuse and Psychiatric Side Effects (2000). Primary 
Care Companion to The Journal of Clinical Psychiatry. 2:159-164. 
Posner K, Brent D, Lucas C, Gould M, Stanley B, Brown G, Fisher P, Zelazny J, Burke A, Oquendo 
M, Mann J. Columbia-Suicide Severity Rating Scale (C-SSRS) Pediatric Baseline Version. New 
York, NY: The Research Foundation for Mental Hygiene, Inc., 2010. 
Owens JA, Spirito A, McGuinn M. The Children’s Sleep Habits Questionnaire (CSHQ): 
psychometric properties of a survey instrument for school-aged children. Sleep, 2000a; 23(8):1043–
51. 
Owens J, Spirito A, McGuinn M, Nobile C. Sleep habits and sleep disturbance in school-aged 
children. Journal of Developmental and Behavioral Pediatrics, 2000b; 21(1):27-36. 
Ritalin® and Ritalin-SR® [Package Insert]. Novartis Pharmaceuticals Corporation. 2015. 
Sellers EM, Romach MK. Categorization of Abuse Potential-Related Adverse Events. Clin 
Pharmacol Drug Dev. 2017 Oct 11. doi: 10.1002/cpdd.394. [Epub ahead of print]. 


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Wilens TE, Biederman J. The stimulants. Psychiatric Clinics of North America. 15:191-222, 
1992. 
Wilens T, Adler LA, Adams J, Sgambati S, Rotrosen J, Sawtelle R, Utzinger L and Fusillo S. 
Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J 
Am Acad Child Adolesc Psychiatry 47: 21-31, 2008. 
 
 


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Appendix A: Instructions for Oral Administration of Study Drug 
• Instructions for taking study drug as a whole capsule 
1. Swallow capsule whole with a cup of water. The capsule needs to be swallowed whole 
(without crushing, cutting, crushing, chewing, opening, or dissolving). Do not swallow the 
capsule without water. 
2. Take more sips of water as needed, up to approximately 8 ounces (240 mL) of water in total. 
 
• Instructions for taking study drug with applesauce: 
1. Place approximately 1-2 tablespoons (~15-30 mL) of applesauce into a clean cup. 
2. Carefully open the capsule and sprinkle the powder onto the applesauce. Discard the capsule 
shell in the garbage. 
3. Swallow the applesauce with study drug right away. Do not save the applesauce with study 
drug for later use. 
4. To make sure that the entire dose is taken, add more water to the cup, swirl and swallow the 
water right away. 
5. Take more sips of water as needed, up to approximately 7 ounces (210 mL) of water in total. 
 
• Instructions for taking study drug with water: 
1. Place approximately 1-2 tablespoons (~15-30 mL) of water into a clean cup. 
2. Carefully open the capsule and empty the powder into the cup of water. Discard the capsule 
shell in the garbage. 
3. Gently swirl the container of water with study drug. 
4. Swallow the water with study drug right away. Do not save the water with study drug for 
later use. 
5. To make sure that the entire dose is taken, add more water to the cup, swirl and swallow the 
water right away. 
6. Take more sips of water as needed, up to approximately 7 ounces (210 mL) of water in total.