Open-Label Study in Stable Schizophrenia Patients to Evaluate the Safety, Tolerability, and Pharmacokinetics of Switching From Oral Risperidone to Risperidone Implant (DLP-114)
Phase: PHASE1
Conditions: Schizophrenia
Sponsor: Delpor, Inc.

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 1 of 101 
 
1 
TITLE PAGE 
PROTOCOL NUMBER: 
DLP-114-03 Revision E 
STUDY TITLE: 
Open-Label Study in Stable Schizophrenia Patients to Evaluate the 
Safety, Tolerability, and Pharmacokinetics of Switching from Oral 
Risperidone to Risperidone Implant (DLP-114) 
INVESTIGATIONAL 
AGENT/DEVICE: 
DLP-114 (Risperidone Implant) 
ROUTE OF 
ADMINISTRATION: 
Subcutaneous implantation of the DLP-114 device 
STUDY DESIGN: 
Open-label, parallel group study to demonstrate a comparable PK 
profile between the marketed oral form of risperidone and 
risperidone administered subcutaneously with the DLP-114 device. 
SPONSOR: 
Delpor, Inc 
150 North Hill Drive, Suite 25 
Brisbane, CA 94005 
 
PRINCIPAL 
INVESTIGATOR (PI): 
Dr. David Walling, CEO, CNS Network, LLC 
SPONSOR 
REPRESENTATIVE 
Dr Frank Martin 
Chief Science Officer, Delpor, Inc. 
STUDY CENTER: 
CNS Network, LLC 
12772 Valley View Street, Suite #3 
Garden Grove, CA, 92845 
 
CONFIDENTIALITY STATEMENT 
Information contained in this protocol should not be disclosed, other than to those directly involved 
in the execution or ethical review of the study, without written authorisation from Delpor Inc. It is, 
however, permissible to provide information to a volunteer in order to obtain consent. 
 
 
COVID-19 
Due to recent developments related to the COVID-19 pandemic, Collaborative Neuroscience 
Research (the clinical research unit [CRU]) has implemented several procedures in accordance 
with the current CDC, WHO, FDA and other public regulatory guidance in order to ensure the 
safety of patients and CRU staff.  These new measures include ensuring that trial participants test 
negative (or only IgG positive) for COVID-19 before they are admitted to the CRU, and practicing 
symptom recognition and monitoring for patients before each CRU visit.  Additional COVID-19 
testing may be conducted during the study at the PI’s discretion.  COVID-19 testing and other 
related assessments are not listed in this protocol as they are not specific to this study.  Additional 
information on the CRU’s COVID-19 policies can be found here:  Policy on Research During the 
COVID-19 Pandemic 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 2 of 101 
 
 
 
EMERGENCY CONTACT INFORMATION 
 
 
SERIOUS ADVERSE EVENT CONTACT INFORMATION 
In case of a serious adverse event (See Section 16.5), the investigator will send a report within 24 
hours of notification to: 
Sponsor Contact 
Dr. Frank Martin  
Chief Science Officer 
Delpor, Inc 
150 North Hill Drive, Suite 25 
Brisbane, CA 94005 
E-mail: frank.martin@delpor.com 
Fax: (415) 480 6871 
Phone: (415) 480 6872 
Mobile: (650) 759 0155 
Sponsor Medical Monitor Contact 
Lawrence Frederick Blob, MD 
Chief Medical Officer 
Cognitive Research Corporation 
200 Central Avenue, Suite 1230 
Saint Petersburg, FL 33701 
lblob@cogres.com 
Fax: (727) 897-9009 
Office: (727) 897-9000 
Mobile: (410) 262-1908 
Contract Research Organization 
 
Cognitive Research Corporation 
200 Central Avenue 
Suite 1230 
Saint Petersburg, FL 33701 
 
 

2 
SPONSOR SIGNATURE PAGE 
Study Protocol 
Protocol No_: DLP-114-03 
Study Title: Open-Label Study in Stable Schizophrenia Patients to Evaluate the Safety, 
Tolerability, and Pharmacokinetics of Switching from Oral Risperidone to Risperidone Implant 
(DLP-114)-
By my signature, I confirm that I have reviewed this protocol and find its content to be 
acceptable. 
SWnature: 
l -) 
Frank Martin 
4.-1 
Chief Science Officer 
Signature: 
Date: 
07/12/2021 
Tassos Nicolaou 
President & Chief Executive Officer 
Delpor Inc 
Page 3 ofl 01 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 4 of 101 
 
 
3 
PRINCIPAL INVESTIGATOR DECLARATION 
 
 
Study Title: Open-Label Study in Stable Schizophrenia Patients to Evaluate the Safety, 
Tolerability, and Pharmacokinetics of Switching from Oral Risperidone to Risperidone Implant 
(DLP-114). 
 
 
DECLARATION 
By my signature, I agree to personally supervise the conduct of this study at my study site and to 
ensure its conduct is in compliance with the protocol, informed consent, Institutional Review 
Board (IRB) procedures, instructions from Delpor Inc representatives, the Declaration of Helsinki, 
ICH Good Clinical Practice Guidelines, and local regulations governing the conduct of clinical 
studies. 
 
 
 
 
 
 
 
 
 
Signature of Site Principal Investigator 
 
Date 
 
Printed Name of Site Principal Investigator 
 
Institution Name: 
 
 
 
 
 
 
 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 5 of 101 
 
 
4 
PROTOCOL SYNOPSIS 
Study Title: 
Open-Label Study in Stable Schizophrenia Patients to Evaluate the 
Safety, Tolerability, and Pharmacokinetics of Switching from Oral 
Risperidone to Risperidone Implant (DLP-114). 
Study Number: 
DLP-114-03 
Phase: 
Phase Ib 
Number of Clinical 
Centers: 
Up to 3 centers in the US 
Study Objective 
(Primary): 
To evaluate the safety and tolerability of DLP-114: 
1) Determine the number and percent of patients experiencing a 
treatment-emergent adverse event; 
2) Evaluate the incidence of local site reactions; 
3) Assess the tolerability of implantation and explantation 
procedures. 
Study Objectives 
(Secondary): 
1) Measure the plasma concentration of risperidone and 9-OH 
risperidone and active moiety (risperidone + 9 OH risperidone) 
following repeated oral administrations. 
2) Measure the plasma concentration of risperidone and 9-OH 
risperidone and active moiety (risperidone + 9 OH risperidone) 
following switch from oral risperidone to subcutaneous 
implantation of two DLP-114 devices. 
3) Measure exploratory treatment outcomes using 2 psychiatric 
rating scales: the Clinical Global Impression (CGI-I) rating 
scale and the PANSS. 
4) Measure the amount of risperidone drug substance remaining in 
the DLP-114 reservoir following its removal, in order to 
estimate average daily output and duration. 
5) Determine average depth of device placement and any potential 
migration. 
Study Population: 
Adult male and female patients between 18 and 70 years of age with a 
diagnosis of schizophrenia and stable for at least 2 weeks on 2-3 
mg/day of oral risperidone will be enrolled. 
Patient Number: 
Two groups of 12-15 schizophrenia patients who are currently on oral 
risperidone therapy (2-3 mg/day), or who are stable on an antipsychotic 
other than oral risperidone (2-3 mg/day) but complete the conversion 
phase, will receive two DLP-114 implants, either the 6-month version 
(Gr 1) or the 12-month version (Gr 2). Therefore, the total number of 
patients enrolled in the study is estimated to be approximately 24-30.  
Study Treatments & 
Route of 
 
Risperdal® (risperidone) - oral administration 
 
DLP-114 (Risperidone Implant - Subcutaneous implantation in a 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 6 of 101 
 
Administration: 
quadrant of the abdomen) 
Number of 
Administrations per 
Treatment: 
Risperdal® (risperidone) – During the conversion phase, subjects who 
are stable on an antipsychotic other than oral risperidone (2-3 mg/day) 
will be tapered off their current antipsychotic and titrated, at the PI’s 
discretion, to oral Risperidone 3 mg/day starting a minimum of 2 weeks 
before implantation. Oral risperidone 1 mg to 3 mg/day will be 
administered at the investigator’s discretion in the conversion phase. 
Risperdal® (risperidone) – Unsupervised administrations of 3 mg/day, 
for 3-6 days (starting 7-10 days before implantation and until 4 days 
before implantation) for subjects who are currently on oral risperidone 
therapy (2-3 mg/day).  
Risperdal® (risperidone) – Supervised administrations of 3 mg/day, for 
six days (4 days before implantation, the day of implantation and the 
day after implantation). 
DLP-114-α4 Implant - Subcutaneous implantation of 2 devices per 
patient for 183 (± 7) days. 
DLP-114-α7 Implant - Subcutaneous implantation of 2 devices per 
patient for 364 (± 7) days. 
Study Duration: 
The study duration for each patient in the study will be up to 236 days 
plus the conversion phase, if applicable, for patients assigned to Group 
1 and 417 days plus the conversion phase, if applicable, for those in 
Group 2. This includes the following: 
 Screening period (up to 28 days) 
 Conversion phase- Cross-titrating, at the PI’s discretion, from 
other antipsychotic(s) to oral risperidone therapy over a 
minimum of 2 weeks to achieve an oral risperidone dose of 3 
mg by Day -14; 
 Unsupervised oral risperidone (3 mg/day) (3-6 days); 
 Supervised oral risperidone (3 mg/day) (4 days); 
 DLP-114 implant treatment, Gr 1 183 [± 7] days; Gr 2 (364 [± 
7] days); 
 Follow-up (7 (± 1) days). 
Study Confinement 
Periods: 
All patients will be confined to the clinical facility at different stages 
for an overall total of up to 9 days.  
Patients will be confined to the clinical facility overnight on Day -1.  
The implantation is scheduled to take place on Day 1 without a 
washout period.  The patient will continue to stay confined in the 
clinical facility until Day 7 (a total of 7 days).   
All patients will be confined to the clinical facility for 2 days at the 
time of implant removal.  
Study Outpatient 
Visits: 
Patients will be required to attend the clinical facility for at least 20 
outpatient visits (Gr 1) and at least 33 outpatient visits (Gr 2) in 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 7 of 101 
 
addition to the screening visit. 
Blood Sample 
Collection: 
An approximate 3 mL of blood will be collected for each PK sampling 
timepoint. 
 
Enrollment Criteria: 
Inclusion Criteria: 
To be eligible for enrolment, patients must meet the following criteria:  
1. Adult patients 18-70 years of age of both sexes diagnosed with schizophrenia or 
schizoaffective disorder according to DSM-V who have been stable on oral risperidone 
(2mg-3mg) for at least 2 weeks. 
      Note: Patients who are stable on an antipsychotic other than oral risperidone (2-3 
      mg/day) and complete the conversion phase may be enrolled. 
2. Patient (and/or a patient's authorized legal representative) has provided written informed 
consent 
3. Patient meets the following criteria: 
a. Outpatient status 
b. PANSS Total Score ≤ 80 at screening. 
c. A score of ≤ 4 on the following PANSS items: 
i. Conceptual disorganization 
ii. Suspiciousness 
iii. Hallucinatory behavior 
iv. Unusual thought content 
v. Hostility 
d. CGI-S ≤ 4 (moderately ill)\Lack of clinically significant suicidal ideation or 
behavior; C-SSRS score type of 4-5 require evaluation by mental health 
professional to ensure patient safety in study 
4. Body Mass Index (BMI) within the range of 18.5 to 40.0 kg/m2 (inclusive); 
5. Ability to understand the nature and objectives of the trial, including risks and adverse 
events, and be able to read, review and sign the informed consent document prior to 
conduct of any study procedures; 
6. Willing and able to comply with the requirements of the study protocol; including 
willingness to visit the clinical facility for all outpatient visits and confinement periods; 
7. Have suitable venous access for blood sampling. 
8. Patient is assessed by the Investigator to be symptomatically stable with regard to pre-
existing medical conditions as evidenced by medical history, non-clinically significant 
findings on physical examination, vital signs, clinical laboratory evaluations (hematology, 
serum chemistries, and urinalysis) or 12-lead electrocardiogram (ECG). Subjects may 
continue on their current prescribed medication regimens to control pre-existing medical and 
psychiatric conditions (other than schizophrenia) including the use of prescribed PRN 
medications. 
Exclusion Criteria: 
1. PANSS score at baseline is ≥ 20% change from screening. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 8 of 101 
 
2. Hospitalized or required acute crisis intervention for symptom exacerbation in the 60 
days prior to admission as determined by the Investigator 
3. Patient has a history of suicide attempt in the last year, or in the opinion of the 
investigator is currently at imminent risk of suicide. 
4. Patient experiencing acute depressive symptoms within the past 30 days, according to the 
Investigator's opinion, that required treatment with an antidepressant 
5. Has a current or recent (within 12 months) DSM-V diagnosis of moderate or severe 
substance use disorder (except for tobacco use disorder) or has a positive urine drug 
screen for prohibited substances at screening. 
6. Have impaired hepatic (ALT/AST >1.5 times higher than the upper limit of normal) or 
renal function (eGFR<50 mL/min) 
7. Previously defined hypersensitivity to Risperidone 
8. History of neuroleptic malignant syndrome (NMS) 
9. Electroconvulsive therapy within 6 months of admission 
10. Requires current use of agents that are strong inhibitors and inducers of cytochrome 
P450; 
11. Known hypersensitivity or allergy to lidocaine or any local anesthetic agent of the amide 
type (local anesthetic used during implant and explant procedures); 
12. Presence of clinically significant skin disorders (such as, but not limited to, skin cancer, 
psoriasis, eczema, or atopic dermatitis), evidence of recent sunburn, scar tissue, tattoo, 
open sore, body piercing or branding at the intended implantation site that would 
interfere with the implantation procedure or interfere with implant site assessments as 
determined by the investigator; 
13. History of clinically significant hypersensitivity or allergic reactions; 
14. Known allergy or hypersensitivity to PABA; 
15. Known allergy or hypersensitivity to parabens, local anesthetics of the ester type, and 
sulfa drugs including antibiotics and thiazide diuretics; 
16. Known hypersensitivity to titanium, implant materials or procedure; 
17. Administration of an investigational drug or device within 1 month prior to first dosing; 
18. Positive result for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibody, or 
HIV antibody; 
19. Pregnant or lactating patients. Positive pregnancy test; 
20. Positive drug test for Methamphetamines, Opiates, Cocaine, Phencyclidine, 
Benzodiazepines, Barbiturates, Methadone, Antidepressants and Amphetamines or 
positive alcohol test at screening or prior to first dose;  
21. Poor CYP2D6 metabolizer; 
22. History of skin picking or delusional parasitosis; 
23. Known history of abnormal scar formation or family history of keloid formation 
 
 
Study Design/Methods: 
This study is a Phase 1b clinical study of DLP-114, a Risperidone Implant product. The study is 
an open-label, parallel group design aimed at assessing the safety, tolerability and PK profile of 
two versions of the DLP-114 drug product, alpha 4, designed to operate for at least 6 months, 
and alpha 7 designed to operate for 12 months.  Eligible patients will be assigned to one of two 
groups following completion of the conversion phase, if applicable, and supervised oral 
risperidone dosing (3mg for 4 days).  Both groups will be switched to 2 DLP-114 devices on 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 9 of 101 
 
Day 1 and safety and PK assessed in parallel for 6 months (Group 1, alpha 4) or 12 months 
(Group 2, alpha 7).  The study also aims to evaluate the utility of DLP-114 in achieving a PK 
profile that is comparable to the marketed oral form of risperidone for either 6 months (DLP-
114-α4) or 12 months (DLP-114-α7). 
Subjects receiving an antipsychotic other than oral risperidone (2-3 mg/day) will be required to 
enter the conversion phase. During the weekly visits in the conversion phase, subjects will cross-
titrate, at the PI’s discretion, from other antipsychotic(s) to oral risperidone therapy over a 
minimum of 2 weeks. The objective of the oral conversion phase is for all subjects to achieve an 
oral risperidone dose of 3 mg by Day -14. 
The study will be conducted in four sequential periods for both groups (subjects will either enter 
the conversion phase or the unsupervised oral risperidone [3 mg/day] period) following 
Screening: 
1. Conversion phase (Cross-titration, at the PI’s discretion, from other antipsychotic(s) to 
oral risperidone therapy over a minimum of 2 weeks to achieve an oral risperidone dose 
of 3 mg by Day -14) 
2. Unsupervised oral risperidone (3 mg/day) 
3. Supervised oral risperidone (3 mg/day)  
4. DLP-114 implant treatment with oral supplement 
5. DLP-114 implant treatment; 
6. Follow-up. 
Each patient enrolled in this study will commence unsupervised dosing with 3 mg/day oral 
risperidone for 3-6 consecutive days, followed by supervised dosing with 3 mg/day oral 
risperidone for 4 consecutive days. Patients who are stable on an antipsychotic other than oral 
risperidone (2-3 mg/day) will enter the conversion phase and cross-titrate, at the PI’s discretion, 
from the other antipsychotic(s) to oral risperidone therapy over a minimum of 2 weeks prior to 
commencing the supervised 3 mg/day oral risperidone for 4 consecutive days. Following the 
conversion, patients will need to be stable on oral risperidone 2-3 mg/day for at least 2 weeks 
prior to being implanted. PK analysis will be conducted following the fourth dose of supervised 
oral risperidone. Two additional oral doses will be administered, one on the day immediately 
prior to implant administration, and another one 24 hours after implant administration. 
Following the completion of the oral phase of the study, each patient in Group 1 will be 
implanted with two DLP-114 alpha 4 devices for 183 (± 7) days and each Group 2 patients will 
receive 2 DLP-114 alpha 7 devices for 364 (± 7) days.  24 hours after implant administration an 
additional oral dose will be administered.  PK analysis will be conducted during the first 72 
hours after implant administration and then daily during the confinement period.  During the 
implant treatment period, patients will return to the clinical facility for outpatient visits for safety 
assessments and sampling for PK. Assessments will include vital signs, physical examination, 
inspection of the site of DLP-114 implantation, ECG, safety laboratory tests, CGI-I, PANSS, C-
SSRS, BARS, SAS, AIMS, assessment of AEs and implant/device events (IDEs), including 
migrations, spontaneous expulsions, and other device-related events, and measurement of body 
weight.  
Pregnancy tests will be conducted (female patients only) to monitor and confirm absence of 
pregnancies. Compliance to study restrictions relating to drugs of abuse will also be monitored 
throughout the dosing and implant periods.  If a serious adverse event is observed the active 
moiety concentration will be measured to evaluate the possibility of dose-dumping. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 10 of 101 
 
For detailed description of schedule of assessments refer to Section 14 (Study Conduct 
Schedules and Guidelines) and Appendix 1 (Overall Schedule of Assessments). 
For detailed description of PK blood collection times (including time point windows) refer to 
Appendix 2 (Pharmacokinetic Sample Collection Schedule). 
 
Dose Administration Stopping Rules for an Individual Subject: 
The Investigator and/or Sponsor may suspend or terminate dose administration upon any of the 
following events: 
 One occurrence of a Serious Adverse Event (SAE) assessed to be probably or possibly 
related to dosing with the investigational product; 
 Two or more severe Adverse Events (AEs) of the same character that are determined to 
be clinically significant by the investigator or sponsor and are assessed as probably or 
possibly related to dosing with the investigational product; 
 Signs of impending relapse 
 
Study Procedures and Assessments:  
Informed Consent. The Patient Information and Consent Form (PICF) will be provided to the 
study participants at screening, prior to any study procedures being performed.  
Medical History. Medical history and demographic data, including name, gender, age, race, 
Body Mass Index (BMI) will be recorded at screening. 
Safety Assessments. This study will assess the safety and tolerability of DLP-114. Safety will 
be determined by evaluating physical examinations, vital signs, ECGs, clinical laboratory 
parameters, clinical ratings (e.g. C-SSRS) and adverse events. Local tolerance at the 
implantation site will be examined and scored for severity of visible signs of 
irritation/inflammation. If deemed necessary, additional safety measurements will be performed 
at the discretion of the investigator (or delegate).  If a serious adverse event is observed the 
active moiety concentration will be measured to evaluate the possibility of dose-dumping.  The 
following assessments will be completed at selected time points (see Section 14 and Appendix 1 
for details) 
 Physical Examination. Complete physical examination performed at screening will 
include, at a minimum, assessment of the following systems: skin, head, ears, eyes, nose 
and throat, respiratory system, cardiovascular system, gastrointestinal system, 
neurological condition, blood and lymphatic systems, and the musculoskeletal system.  
 Implantation site inspection will be by visual and physical examination at each 
assessment visit. The physician will palpate the device to determine whether it has 
migrated by noting a change in distance from the incision site to the proximal end of the 
device. Healing of the incision will be monitored. Dermal reactions will be scored on a 
Skin Irritation Scoring System (Appendix 3) [1] recommended for transdermal dosage 
forms that describes the amount of erythema, edema, and other features indicative of 
irritation. 
 Electrocardiogram. Single 12-lead ECG will be performed at selected time points. The 
following variables will be provided automatically: RR, PR, QRS, QT and QTcF 
intervals and pulse rate. In case of evident bad quality (muscle tremor) of the tracing, the 
ECG will be repeated. All ECGs should be obtained prior to vital signs and blood 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 11 of 101 
 
sampling when applicable. 
 Vital Signs. Vital signs will be performed at selected time points. Assessments will 
include systolic and diastolic blood pressure, pulse, body temperature, respiratory rate 
and orthostatic blood pressure and pulse at selected timepoints.  
 Safety Laboratory Tests. The following clinical laboratory safety tests will be performed: 
o Hematology. Leukocytes, erythrocytes, haemoglobin, haematocrit, thrombocytes; 
(partial automated differentiation): lymphocytes, monocytes, eosinophils, 
basophils, neutrophils. 
o Serum Chemistry. Sodium, potassium, calcium, phosphate, blood urea nitrogen 
(BUN), serum creatinine, glucose, lactic acid dehydrogenase (LDH), alanine 
transferase (ALT), aspartate transferase (AST), total bilirubin, alkaline 
phosphatase, gamma glutamyl transferase (GGT), total proteins, albumin and 
urates. Lipid profile: total cholesterol, LDL, HDL, non-HDL and triglycerides. 
o Coagulation. Prothrombin time (PT), international normalized ratio (INR) and 
activated partial thromboplastin time (aPTT). 
o Urinalysis. Urine sample for urinalysis will be collected at specified time points. 
The following urinalysis parameters will be assessed: hemoglobin, urobilinogen, 
ketones, bilirubin, glucose, protein, nitrite, leukocytes, pH, specific gravity.  
 Ultrasound. To determine depth of device placement. 
 CYP2D6 genotyping 
 Viral Serology. Hepatitis B surface antigen, hepatitis C antibody and HIV screen. 
 Pregnancy Test (Females only): serum human chorionic gonadotropin (hCG) at the 
screening visit and urine hCG test at all subsequent visits.  
 Alcohol and Drugs of Abuse Screen. Alcohol breath test will be conducted at screening 
and prior to first dose. Urine drug test will include screen for: Methamphetamines, 
Opiates, Cocaine, Phencyclidine, Benzodiazepines, Barbiturates, Methadone, Tricyclic 
Antidepressants and Amphetamines. 
 C-SSRS will be administered each visit; additional evaluation by a mental health 
professional may follow 
 EPS (Bars, SAS and AIMS)  
 CGI-I will be administered at least every 4 weeks 
 PANSS will be administered at least every 3 months. If CGI-I worsens, PANSS will be 
administered more frequently 
Pharmacokinetics. Determination of plasma concentrations of risperidone, 9-OH risperidone 
and active moiety (risperidone + 9 OH risperidone) on the last day of oral risperidone treatment, 
throughout the duration of the DLP-114 implant treatment and following removal of the DLP-
114 implants.  
 
Study Endpoints: 
Safety endpoints include: 
 Incidence and severity of AEs; 
 Local tolerance at the implantation site will be examined and scored for severity of 
visible signs of irritation/inflammation; 
 Tolerability of the implantation and explantation procedures; 
 Vital signs parameters; 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 12 of 101 
 
 Physical examination findings; 
 Electrocardiogram parameters; 
 Safety laboratory test parameters (serum chemistry, hematology, urinalysis); 
 Exploratory treatment outcomes will be assessed using 2 psychiatric rating scales: the 
Clinical Global Impression (CGI-I) rating scale and the PANSS. 
Pharmacokinetic Endpoints include the evaluation of plasma concentrations of risperidone, 9-
OH risperidone and active moiety (risperidone + 9 OH risperidone).  
PK parameters to be calculated for oral risperidone treatment period include: 
 Maximum concentration (Cmax); 
 Minimum concentration (Cmin) 
 Time to maximum concentration (Tmax); 
 Time to minimum concentration (Tmin) 
 Average concentration (Cave) 
 Area under the plasma concentration vs. time curve (AUC) 
PK parameters to be calculated for implant treatment period include:  
 Maximum concentration (Cmax); 
 Minimum concentration (Cmin) 
 Time to maximum concentration (Tmax); 
 Time to minimum concentration (Tmin); 
 Average concentration (Cave) 
 Area under the plasma concentration vs. time curve (AUC) 
Device Endpoints include: 
 Implant spontaneous migration away from the initial subcutaneous implantation area 
during the implant treatment period. 
 Amount of unreleased drug substance remaining in the DLP-114 implant following its 
removal in order to estimate average daily output. 
 Average depth of device placement 
 
Statistics and Data Analyses: 
Sample Size Considerations. The maximum sample size is 24-30. The primary objective of this 
study is to determine safety and tolerability of two versions of the DLP-114 implant (one 
designed for 6 months and the other designed to operate for 1 year) and as such the sample size 
for this study was based upon qualitative considerations. No formal sample size calculations 
were performed.  
Demographic Data. For all patients who received at least 1 dose of study treatment, descriptive 
statistics (mean, standard deviation, median, minimum, maximum) will be performed for age, 
gender, body mass index, weight, and height.  
Safety/Tolerability Data. All patients who receive at least 1 dose of study treatment will be 
included in the safety and tolerability analysis. Baseline for all vital signs, 12-lead ECG 
measurements, and clinical laboratory assessments will be defined as the last evaluation done 
before the start of study treatment administration on Day -5. Safety evaluations will be based on 
the incidence, intensity and type of AE and clinically significant changes in the patient’s 
physical examination findings, vital signs, 12-lead ECGs, and clinical laboratory results. Safety 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 13 of 101 
 
variables will be tabulated and presented for all patients who receive study treatment. 
Abnormalities in clinical laboratory, vital signs, and ECG will be based on pre-defined normal 
ranges and will be tabulated by study treatment showing patient counts and percentages. The 
original terms used in the CRF by investigators to identify AEs will be coded using the current 
version of the Medical Dictionary of Regulatory Activities (MedDRA). The percentage of 
patients with treatment-emergent AEs will be summarized for each treatment. Laboratory data 
will be summarized by the type of laboratory test. Normal reference ranges and markedly 
abnormal results will be used in the summary of laboratory data. Raw data and change from 
baseline in clinical laboratory parameters will be summarized using descriptive statistics. A 
listing of patients with any laboratory results outside the reference ranges that are deemed 
clinically significant will be provided. 
Pharmacokinetic Data. Plasma concentrations of risperidone, 9-OH risperidone and active 
moiety (risperidone + 9 OH risperidone) determined at specified time points will be used to 
calculate PK parameters. Data will be listed for all patients with available plasma concentrations 
of risperidone, 9-OH risperidone and active moiety (risperidone + 9 OH risperidone). 
Pharmacokinetic parameters for risperidone, 9-OH risperidone and active moiety (risperidone + 
9 OH risperidone) will be calculated using non-compartmental analysis. Listing of individual 
patient plasma concentrations, actual blood sampling times, and PK parameters and graphs of 
concentration vs. time will be prepared by study treatment. Plasma concentrations and PK 
parameters will be summarized by and compared between study treatments using descriptive 
statistics. Statistical analysis will be performed on the pharmacokinetic parameters using 
validated statistical software. If a serious adverse event is observed the active moiety 
concentration will be measured to evaluate the possibility of dose-dumping. 
 
 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 14 of 101 
 
5 
TABLE OF CONTENTS 
 
1 
TITLE PAGE .................................................................................................................... 1 
2 
SPONSOR SIGNATURE PAGE .................................................................................... 3 
3 
PRINCIPAL INVESTIGATOR DECLARATION ....................................................... 4 
4 
PROTOCOL SYNOPSIS ................................................................................................. 5 
5 
TABLE OF CONTENTS ............................................................................................... 14 
6 
LIST OF ABBREVIATIONS AND TERMS ............................................................... 19 
7 
INTRODUCTION .......................................................................................................... 21 
7.1 
Background Information ............................................................................................ 21 
7.2 
Proposed Clinical Application ................................................................................... 21 
7.3 
Non-clinical Safety, Toxicology and Pharmacokinetics ............................................ 21 
7.4 
Clinical Experience .................................................................................................... 35 
7.5 
Risk/Benefit Assessment and Guidance for Investigators ......................................... 35 
8 
STUDY OBJECTIVES .................................................................................................. 38 
8.1 
Primary ....................................................................................................................... 38 
8.2 
Secondary ................................................................................................................... 38 
9 
STUDY DESIGN ............................................................................................................ 39 
9.1 
Design Type and Description ..................................................................................... 39 
 
Unsupervised oral risperidone period (Day -7 to -5) ...................................................................... 41 
 
Oral risperidone conversion phase (minimum of 2 weeks prior to implant) .................................. 41 
 
Supervised oral risperidone period (days -4 to 1) ........................................................................... 41 
 
DLP-114 implant treatment period with oral supplement (Days 1 to 2) ........................................ 41 
 
DLP-114 implant treatment period (days 2-183 [± 7] for Gr 1, or days 2-365 [± 7] for Gr 2) ....... 41 
 
Follow-up and End of Study Visits (7 days [±1] after device removal) ......................................... 42 
9.2 
Dose Administration Stopping Rules for an Individual Subject ................................ 42 
9.3 
Suspension or Termination of Study at the Investigational Site ................................ 43 
9.4 
Randomization and Blinding ...................................................................................... 43 
9.5 
Endpoints .................................................................................................................... 43 
 
Safety Endpoints ............................................................................................................................. 43 
 
Pharmacokinetic Endpoints ............................................................................................................ 43 
 
Exploratory Treatment Outcomes .................................................................................................. 44 
 
Device Endpoints ........................................................................................................................... 44 
9.6 
Duration of the Study ................................................................................................. 44 
9.7 
Study Design Rationale .............................................................................................. 45 
10  PATIENT SELECTION ................................................................................................ 45 
10.1  Number of Patients ..................................................................................................... 45 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 15 of 101 
 
10.2  Inclusion Criteria ........................................................................................................ 45 
10.3  Exclusion Criteria ....................................................................................................... 46 
10.4  Patient Withdrawal Criteria ........................................................................................ 47 
10.5  Patient Replacement ................................................................................................... 47 
11  INVESTIGATIONAL PRODUCT ............................................................................... 48 
11.1  Identification and Description .................................................................................... 48 
11.2  Investigational Substance ........................................................................................... 48 
11.3  Identification and Description of Reference Product ................................................. 49 
11.4  Description of the Investigational Device .................................................................. 49 
11.5  Implanter Tool ............................................................................................................ 50 
11.6  Preparation, Labelling and Supply ............................................................................. 50 
11.7  Storage, Handling and Accountability of Investigational and Reference Products ... 50 
 
DLP-114 Storage and Handling ..................................................................................................... 50 
 
Risperdal® Storage and Handling ................................................................................................... 50 
 
Accountability ................................................................................................................................ 50 
12  ADMINISTRATION OF INVESTIGATIONAL PRODUCTS ................................. 51 
 
Oral Risperidone Administration .................................................................................................... 51 
 
DLP-114 Implantation .................................................................................................................... 52 
13  CONCOMITANT MEDICATIONS AND OTHER RESTRICTIONS .................... 53 
13.1  Concomitant Medications .......................................................................................... 53 
13.2  Contraception ............................................................................................................. 54 
13.3  Exercise ...................................................................................................................... 54 
13.4  Caffeine, and Alcohol ................................................................................................ 54 
14  STUDY PROCEDURES AND ASSESSMENTS ......................................................... 54 
14.1  Informed Consent ....................................................................................................... 54 
14.2  Medical History .......................................................................................................... 54 
14.3  Safety Assessments .................................................................................................... 54 
 
Physical Examination ..................................................................................................................... 55 
 
Implantation Site Inspection and Wound Care ............................................................................... 55 
 
Electrocardiogram .......................................................................................................................... 55 
 
Vital Signs ...................................................................................................................................... 55 
 
Safety Laboratory Tests .................................................................................................................. 56 
 
Viral Serology ................................................................................................................................ 56 
 
Pregnancy Test ............................................................................................................................... 56 
 
Alcohol and Drugs of Abuse Screen .............................................................................................. 57 
 
Ultrasound ...................................................................................................................................... 57 
  C-SSRS, CGI-1 and PANSS, ......................................................................................................... 57 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 16 of 101 
 
  EPS ................................................................................................................................................. 59 
  Signs of impending relapse ............................................................................................................ 60 
  Video Recording ............................................................................................................................. 60 
14.4  Pharmacokinetics ....................................................................................................... 60 
14.5  Total Blood Sample Volumes .................................................................................... 61 
15  STUDY CONDUCT SCHEDULES AND GUIDELINES .......................................... 61 
15.1  Screening, Selection and Consent .............................................................................. 61 
15.2  Clinical Conduct (Day -7 to Day -5): Groups 1 and 2 ............................................... 62 
15.3  Clinical Conduct (Weekly Visits for a minimum of 2 weeks through Day -14): Groups 1 
and 2 62 
15.4  Clinical Conduct (Days -4 to 4): Groups 1 and 2 ....................................................... 62 
 
DAY -4 (outpatient visit) ................................................................................................................ 62 
 
DAY -3 and DAY -2 (outpatient visits) ......................................................................................... 63 
 
DAY -1 (confinement to the clinical facility) ................................................................................. 63 
 
DAY 1 (DLP-114 implantation day, confinement to the clinical facility) ..................................... 63 
 
DAY 2 (confinement to the clinical facility) .................................................................................. 64 
 
DAY 3 (confinement to the clinical facility) .................................................................................. 64 
 
DAY 4-6 (confinement to the clinical facility) ............................................................................... 64 
 
DAY 7 (discharge) ......................................................................................................................... 65 
15.5  Clinical Conduct (Days 14 to End of Study) – Group 1 ............................................ 65 
 
DAYS 14, 21, 28, 42, 56, 70, 84, 98, 112, 126, 140, 154, and 168 (outpatient visits) ................... 65 
 
DAY 183 (± 7 days) (confinement to the clinical facility) ............................................................. 66 
 
DAY 184 (confinement to the clinical facility ) ............................................................................. 66 
 
DAY 185 (confinement to the clinical facility ends) ...................................................................... 67 
 
DAY 186 (outpatient visit) ............................................................................................................. 67 
 
DAY 190 (End of Study, outpatient visit) ...................................................................................... 67 
15.6  Clinical Conduct (Days 14 to End of Study) – Group 2 ............................................ 67 
 
DAYS 14, 21, 28, 42, 56, 70, 84, 98, 112, 126, 140, 154, 168, 182, 196, 210, 224, 238, 252, 266, 280, 
294, 308, 322, 336, and 350 (outpatient visits) .............................................................................. 67 
 
DAY 364 (± 7 days) (confinement to the clinical facility) ............................................................. 68 
 
DAY 365 (confinement to the clinical facility) .............................................................................. 69 
 
DAY 366 (confinement to the clinical facility ends) ...................................................................... 69 
 
DAY 367 (outpatient visit) ............................................................................................................. 69 
 
DAY 371 (End of Study, outpatient visit) ...................................................................................... 70 
15.7  Early Termination Procedures .................................................................................... 70 
15.8  Timing of Treatments and Procedures ....................................................................... 71 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 17 of 101 
 
16  ASSESSMENT AND MANAGEMENT OF ADVERSE EVENTS ........................... 71 
16.1  Adverse Event Definitions ......................................................................................... 71 
16.2  Evaluating AE and SAE ............................................................................................. 72 
 
Assessment of Causality ................................................................................................................. 73 
 
Action Taken and Outcome ............................................................................................................ 73 
16.3  Procedures and Time Period for Detecting Adverse Events ...................................... 74 
16.4  Recording of AEs and SAEs ...................................................................................... 74 
16.5  Reporting of SAEs and SUSARs ............................................................................... 75 
16.6  Follow-up of AE and SAE ......................................................................................... 75 
16.7  Exposure In Utero Management and Reporting ........................................................ 76 
17  PATIENTS LOST TO FOLLOW-UP AFTER IMPLANTATION .......................... 76 
18  STATISTICS AND DATA ANALYSIS ....................................................................... 77 
18.1  Sample Size Considerations ....................................................................................... 77 
18.2  Demographic Data ..................................................................................................... 77 
18.3  Safety/Tolerability Data ............................................................................................. 77 
18.4  Pharmacokinetic Data ................................................................................................ 78 
19  DATA HANDLING AND RECORDKEEPING ......................................................... 78 
19.1  Patient Identification and Enrolment Log and Patient Screening Log ....................... 78 
19.2  Source Documentation ............................................................................................... 79 
19.3  Case Report Form ...................................................................................................... 79 
20  ETHICS AND REGULATORY COMPLIANCE ....................................................... 79 
20.1  Investigator Responsibilities ...................................................................................... 79 
20.2  Independent Ethics Committee or Institutional Review Board (IEC/IRB) ................ 79 
20.3  Required Pre-study Documentation ........................................................................... 80 
20.4  Clinical Laboratory Certification and Reference Ranges .......................................... 80 
20.5  Informed Consent ....................................................................................................... 80 
20.6  Privacy of Personal Data ............................................................................................ 81 
20.7  Study Completion/Site Closure .................................................................................. 81 
21  QUALITY CONTROL AND ASSURANCE ............................................................... 81 
21.1  Study Monitoring ....................................................................................................... 81 
21.2  Audits, Inspections Study Quality Management ........................................................ 81 
21.3  Data Quality Control .................................................................................................. 82 
21.4  Record Retention ........................................................................................................ 82 
22  STUDY PROTOCOL GUIDELINES .......................................................................... 82 
22.1  Protocol Amendments, Deviations and Violations .................................................... 82 
23  USE OF INFORMATION AND PUBLICATION POLICY ..................................... 83 
24  LIABILITY AND INSURANCE .................................................................................. 84 
25  REFERENCES ............................................................................................................... 84 
26  APPENDICES ................................................................................................................ 85 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 18 of 101 
 
26.1  APPENDIX 1. Overall Schedule of Assessments ...................................................... 85 
26.2  APPENDIX 2. Pharmacokinetic Sample Collection Schedule .................................. 88 
26.3  APPENDIX 3. Skin Irritation Scoring System .......................................................... 91 
26.4  APPENDIX 4. Risperdal® (risperidone) Product Information ................................. 92 
26.5  APPENDIX 5. Instructions for Use (IFU) ................................................................. 99 
26.6  APPENDIX 6. DLP-114 Labels .............................................................................. 100 
 
 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 19 of 101 
 
6 
LIST OF ABBREVIATIONS AND TERMS 
AE 
Adverse Event 
ADL 
Activities of daily living 
AIMS 
Abnormal Involuntary Movement Scale 
ALT 
Alanine aminotransferase  
aPTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate aminotransferase 
BARS 
Barnes Akathesia Rating Scale 
BMI 
Body Mass Index 
BUN 
Blood Urea Nitrogen 
Cave 
Average concentration 
Cmax 
Concentration maximum (peak) 
CFR 
Code of Federal Regulations 
CGI-I 
Clinical Global Impression Scale – Improvement 
CGI-S 
Clinical Global Impression Scale – Severity 
CNS 
Central Nervous System 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
DCF 
Data Correction Forms 
DSMC 
Data and Safety Monitoring Committee 
ECG 
Electrocardiogram 
EIU 
Exposure In Utero 
CRF 
Case Report Form 
EOS 
End of Study 
EPS 
Extrapyramidal Symptoms 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
Gamma glutamyl transferase 
HbA1c 
Hemoglobin A1c 
HBsAg 
Hepatitis B surface antigen 
hCG 
Human Chorionic Gonadotropin 
HCV 
Hepatitis C antibodies 
HDL 
High density lipoprotein 
HIV 
Human Immunodeficiency Virus 
HREC 
Human Research Ethics Committee 
ICH 
International Conference on Harmonization  
IDE 
Implant/Device Event 
IEC 
Independent Ethics Committee 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
LDH 
Lactic Acid Dehydrogenase 
LDL 
Low Density Lipoprotein 
LOQ 
Limit of Quantification 
MAOI 
Monoamine oxidase inhibitors 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 20 of 101 
 
MedDRA 
Medical Dictionary of Regulatory Activities 
NHANES 
National Health and Nutrition Examination Survey 
PABA 
Para-aminobenzoate 
PANSS 
Positive and Negative Syndrome Scale 
PBS 
Phosphate-buffered saline 
PICF 
Patient Information and Consent Form 
PK 
Pharmacokinetic 
PT 
Prothrombin Time 
PVDF 
Polyvinylidene difluoride 
PVP40 
Polyvinylpyrrolidone 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
RSQ 
Risperidone Symptom Questionnaire 
SAE 
Serious Adverse Event 
SAS 
Simpson-Angus Scale 
SUSAR 
Suspected Unexpected Adverse Reaction 
THC 
Tetrahydrocannabinol 
Tmax 
Time at which the Cmax is observed 
 
 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 21 of 101 
 
7 
INTRODUCTION 
7.1 Background Information 
Risperidone is an antipsychotic whose primary therapeutic activity is postulated to be mediated 
through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) antagonism.  
Risperidone is currently marketed as immediate-release tablets, orally disintegrating tablets, an 
oral solution and as a long-acting intramuscular injection.  
DLP-114 is a Risperidone Implant that is a combination drug-device product designed to 
continuously elute the equivalent of a daily 1-2 mg oral dose of risperidone following 
subcutaneous implantation. The device is implanted in a quadrant of the abdomen at least 5cm 
from midline and 5 cm below the ribs, using a sterile disposable implanter tool and local 
anesthesia in a minimally invasive procedure. 
Each DLP-114 device consists of a hollow cylindrical titanium reservoir (similar in materials, size 
and shape, to other approved implants) that is fitted on each end with a cap containing a 0.1 
micron membrane and filled with tablets of a homogenous powder form of risperidone plus a two-
time molar excess of para-aminobenzoic acid (PABA). To aid with tableting the formulation, 
PVP40 and stearic acid are added. Drug release is achieved by a novel passive diffusion 
mechanism initiated by the introduction of sterile saline.  Two versions of the DLP-114 device 
will be tested in the IND study.  The devices are loaded with the same risperidone formulation 
(RISP/PABA 1:2), are the same diameter, have the same membrane diffusive surface area, but 
differ in the length of the reservoir and in vivo operating period.  DLP-114-α4 is 44 mm in length 
and designed to operate for 6 months. DLP-114-α7 is 50 mm long and designed to operate for 12 
months. 
7.2 Proposed Clinical Application  
Risperidone, is currently approved for acute and maintenance therapy of schizophrenia and, as 
monotherapy or adjunctively, in the acute treatment of Bipolar Disorder I. It is also approved for 
the management of irritability in pediatric and adolescent patients with autistic disorder. The 
DLP-114 drug-device is appropriate for maintenance therapy rather than acute therapy and thus it 
is being developed as a maintenance treatment for schizophrenia in adults. 
7.3 Non-clinical Safety, Toxicology and Pharmacokinetics 
The PK and local tolerance of DLP-114 has been tested preclinically in two species, rat and 
rabbit.  A total of 7 non-clinical studies have been completed testing the Pharmacokinetics, 
Toxicity and Tissue Compatibility of DLP-114.  Table 1 below provides a summary of the 
studies conducted.  
 
Table 1: Summary of in vivo Non-Clinical Studies with DLP-114 
Animal 
Study 
GLP? 
Group 
Number 
Formulation 
Device 
Type 
Length 
of 
Implant 
(days) 
Output 
Rate in 
vivo 
(mg/day) 
Observations 
 
 
 
 
7 
RISP/PABA 
1:3 
1-ended 
α2 
119 
(n=5) 
0.29 
No to mild 
local tissue 
reactivity; no 
adverse 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 22 of 101 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No 
treatment-
related clinical 
observations 
8 
RISP/PABA 
1:2 
α3 
119 
(n=4) 
0.80 
No to mild 
local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
9 
RISP/PABA 
1:2 
α2 
119 
(n=1) 
183 
(n=5) 
0.70 
No to mild 
local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
10 
RISP/PABA 
1:2 
α1 
119 
(n=4) 
183 
(n=6) 
0.46 
No to mild 
local tissue 
reactivity; one 
self-explant, 
otherwise no 
adverse 
treatment-
related clinical 
observations 
11 
RISP/PABA 
1:2 
1- 
ended 
α2 
183 
(n=5) 
0.42 
No to mild 
local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
PLGA Mix 
C 
α2 
124 
(n=5) 
0.86 
No to mild 
local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
2 
PLGA Mix 
C 
α3 
124 
(n=5) 
0.79 
No to mild 
local tissue 
reactivity; no 
adverse 
treatment-

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 23 of 101 
 
 
 
 
 
 
 
 
 
 
13 
 
 
 
 
 
 
 
 
 
No 
related clinical 
observations 
3 
RISP/PABA 
1:2 
α2 
278 
(n=5) 
0.68 
No to mild 
local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
other than one 
spontantaneous 
explantation 
4 
Sebacic 
Acid 
α3 
180 
(n=5) 
0.98 
No to mild 
local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
5 
Risperidone 
Acetate 
ALZET 
pump 
31 
(n=5) 
N/A 
No to mild 
local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
RISP/PABA 
1:2 
2 α2 
92 
(n=5) 
0.98 
No to 
moderate local 
tissue 
reactivity; 
animals 
appeared 
lethargic for 12 
days post 
implant, 
normal 
afterwards; 
animal 
1001partially 
explanted a 
device 
multiple times 
2 
RISP/PABA 
1:2 
2 α2 
92 
(n=5) 
0.97 
No to 
moderate local 
tissue 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 24 of 101 
 
 
14 
 
No 
reactivity; 
animal 2003 
partially 
explanted a 
device, and 
then fully 
explanted it the 
following day 
after re-
insertion; 
animal 2005 
was discovered 
moribund and 
subject to 
euthanasia, it 
is unclear if 
this is related 
to test article 
 
 
 
 
 
15 
 
 
 
 
 
Yes 
1 
Placebo 
α2 
30 
(n=2) 
N/A 
No local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
2 
RISP/PABA 
1:2 
α2 
30 
(n=8) 
1.58 
No to 
moderate local 
tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
 
 
 
 
 
 
 
16 
 
 
 
 
 
 
 
No 
1 
RISP/PABA 
1:2 
α2 
273 
(n=5) 
0.58 
No to mild 
local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
2 
RISP/PABA 
1:2 
α2 
273 
(n=5) 
0.51 
No to 
moderate local 
tissue 
reactivity; no 
adverse 
treatment-
related clinical 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 25 of 101 
 
observations 
 
 
 
 
 
 
 
 
19 
 
 
 
 
 
 
 
 
No 
1 
RISP/PABA 
1:2 
(12%PVP) 
α2 
183 
(n=5) 
0.56 
No local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations  
2 
RISP/PABA 
1:2 
(5%PVP) 
α2 
364 
(n=5) 
0.37 
No to mild 
local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
other than one 
spontaneous 
explant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
RISP/PABA 
1:2 
α2 
182 
(n=6) 
0.65 
No to 
moderate local 
tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
other than one 
spontaneous 
explantation 
2 
RISP/PABA 
1:2 
α4 
182 
(n=12) 
0.72 
No local tissue 
reactivity; one 
animal (2003) 
was found 
dead on day 
20, otherwise 
no adverse 
treatment-
related clinical 
observations 
3 
RISP/PABA 
1:3 
α4 
182 
(n=12) 
0.57 
No to 
moderate local 
tissue 
reactivity; no 
adverse 
treatment-
related clinical 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 26 of 101 
 
20 
Yes 
observations 
other than one 
spontaneous 
explantation 
4 
Placebo 
α4 
182 
(=12) 
N/A 
No local tissue 
reactivity; no 
adverse 
treatment-
related clinical 
observations 
 
DLP-ASR-0012:  This study was proposed to compare different formulations, 
mechanisms, and devices in order to optimize risperidone output. It compared 3 types of devices 
(α1, α2, and α3), as well as the pre-clinical prototype device for comparison. Formulations 
included risperidone hexanoate salts mixed with PLGA copolymers, and risperidone free based 
mixed with molar excesses of 2 or 3 time para-aminobenzoic acid (PABA). The devices were 
implanted for 119 or 183 days, and evaluated by plasma concentration over time, clinal 
observations, and post-explant tissue necropsy and histopathology. From the PK it can be 
concluded that the output from single ended devices is not optimal, and that a double-ended 
device is likely needed to achieve sufficient output for a clinical device. The risperidone PABA 
output from the double-ended devices had a burst effect in groups 8-10, but the output achieved 
steady state by week 2, at about 3 times below the Cmax. The plasma concentration remained fairly 
flat for the remainder of the implant period. The average plasma concentrations of groups 8 and 9 
were, and both were higher than that of group 10. Taken together, these results indicate the best 
clinical product for risperidone using this technology would be risperidone with a 2-fold molar 
excess of PABA. It was also noted that the device was well tolerated in rats, with one self 
explantation (Group 10, α1 device), but otherwise no adverse treatment-related clinical 
observations and no (score of 1 out of 5) to mild (score of 2 out of 5) local tissue reactivity at 
necropsy.  
 
DLP-ASR-0013: This study was proposed to study the viability of a risperidone PABA 2 
times molar excess formulation over a 9 month period in rats, as well as to compare that 
formulation with a previously used formulation, “Mix C”, and to a formulation that involved a 
diprotic acid, sebacic acid. This study also included the use of an ALZET pump configured to 
released risperidone acetate at a rate equivalent to 1mg of risperidone base/day for 30 days. The 
ALZET group was mainly used to correlate plasma concentrations of risperidone active moiety to 
a known control. The devices were implanted for 124, 180, or 278 days, and evaluated by plasma 
concentration over time, clinal observations, and post-explant tissue necropsy and histopathology. 
Based on the PK profile, it was estimate that the lifespan of the risperidone PABA device (α2 
device loaded with 480mg of risperidone PABA 1:2) was 8 months before it dipped below the 50 
ng/ml threshold. This study again reiterated that the device is well tolerated with minimal 
discomfort and no test-article related clinical observations or adverse body weight effects. One 
animal self-explanted on Day 231. Necropsy findings found no to mild inflammation in the tissue 
surrounding the implant site.  
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 27 of 101 
 
DLP-ASR-0014: This study was proposed to study whether implanting additional devices 
resulted in a linear increase in plasma concentration in vivo. This study also compared devices 
made by Delpor, and those made by a CMO, Hantel, to determine if manufacturing transfer was 
successful. The devices were implanted for 92 days, and evaluated by plasma concentration over 
time, clinal observations, and post-explant tissue necropsy and histopathology. Based off the 
results of this study comparing devices prepared by Delpor and those prepared by the CMO, the 
transfer of the production process to the CMO was successful. This study demonstrated that the 
doses of DLP-114 can be additive; by comparing the plasma concentrations of this study against 
those of group 9 from DLP-ASR-0012, we can see that animals implanted with two devices had 
approximately double the plasma concentration of those implanted with one device. It was also 
noted that rats may not be an appropriate species for studying the implantation of two devices, 
given the one complete and two partial explantations during the study in the double implant 
groups. Local tissue reactivity ranged from no reactivity to moderate reactivity (score of 3 out of 
5). One animal (2005) was discovered moribund and subject to euthanasia per veterinary 
guidelines; it is unclear whether this adverse event was related to the implant device. Otherwise, 
there were no adverse treatment-related clinical observations.  
 
DLP-ASR-0015: This GLP study was proposed in order to study the pharmacokinetics, 
safety, and tissue compatibility of DLP-114 in female New Zealand White (NZW) rabbits. Two 
rabbits were implanted with an empty placebo device, while eight were implanted with a single 
DLP-114 device. The devices were implanted for 30 days, and evaluated by plasma concentration 
over time, clinal observations, and post-explant tissue necropsy and histopathology. Based on the 
results of this study, surgical subcutaneous implantation of a single α2 device containing the 
placebo (1X PBS) or the test article (RISP/PABA 1:2, ~250 mg of active drug/device) in the inter 
scapular region of the New Zealand White rabbits was well tolerated and did not result in 
evidence of overt toxicity (animal observation or body weight changes) or evidence that the 
device caused physical irritation or discomfort (control or test device). In fact, there were no 
visible indications that the animals were aware of the presence of the device. Gross necropsies 
conducted 30 days post-implantation revealed either no visual inflammatory response in the 
tissues surrounding the device (both control animals and 2 of 7 risperidone treated animals), or a 
slight to moderate tissue response (remaining 5 of 7 risperidone treated animals). Capsule 
formation surrounding the implant in each animal was clear and thin. Histopathology was 
conducted on the tissues taken directly adjacent to the test or placebo device. The pathologist 
concluded that the slow-release risperidone implants (RISP/PABA 1:2, 250 mg of active drug) 
produced significantly more inflammation in the subcutis of the test rabbits than was evident in 
the control rabbits. The lesions were consistent with persistent irritation resulting in necrosis of 
the adipocytes, pyogranulomatous inflammation and healing by fibrosis. However, it is important 
to note that the microscopic findings are for tissue taken directly adjacent to the test or control 
device. As is evidenced in the photos, the areas of inflammation were visibly very small and 
sometimes not visible at all (control and test animals).  In addition, the clinical observations did 
not reveal any evidence that the devices caused physical irritation or discomfort to any animals 
(control or test device). One animal broke its back on day 1 during a restrained blood draw, was 
euthanized and therefore excluded from PK analysis.  
 
DLP-ASR-0016: This non-GLP study was proposed in order to investigate whether a 
change in hydration medium from 1X PBS to 0.9% saline affected device performance. This 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 28 of 101 
 
study also utilized the same lot of DLP-114 that was used in the first-in-man study of DLP-114 in 
Australia. The devices were implanted for 273 days, and evaluated by plasma concentration over 
time, clinal observations, and post-explant tissue necropsy and histopathology. The results of this 
study indicate that there is no difference in PK profile between devices hydrated with PBS or with 
saline, and that all devices were well tolerated. These devices were the same devices used in a 
clinical trial, allowing for an important comparison between output in rats and output in humans. 
The average tissue reactivity score was between no inflammation and mild inflammation (1.6), 
and output was 0.5-0.6 mg/device/day. No adverse treatment-related clinical observations were 
reported, again demonstrating tolerance of extended implantation with the DLP-114 device.  
 
DLP-ASR-0019: The purpose of this study was to investigate whether lowering the 
percentage of PVP used in the formulation as a binder influenced device performance. A lower 
amount of PVP would leave more room for risperidone to be loaded in the final product, allowing 
for a longer effective life of the product. The wt% of PVP was investigated at 12% in one group 
and 5% in another. The devices were implanted for 183 (group 1) or 364 (group 2) days, and 
evaluated by plasma concentration over time, clinal observations, and post-explant tissue 
necropsy and histopathology. The results of this study indicate there was no difference between 
devices filled with a drug formulation composed of 12% PVP and one composed of 5% PVP. 
This allows for a longer life of the device, reflecting the longer implant lengths of group 2. The 
devices were again well tolerated (average necropsy score 1.5), with implantation lasting up to 
364 days. There was one spontaneous explantation in group 2. There were no adverse treatment-
related clinical observations otherwise.  
 
DLP-ASR-0020: This GLP study compared the device used in Delpor’s first-in-man 
clinical trial, α2, with the same formulation in a longer device with a larger exposed membrane 
area, α4, and a formulation with a 3 fold molar excess of PABA (RISP/PABA 1:3) in the larger 
α4 device. This study also included a placebo α4 group. The purpose of this study was to 
determine whether the larger α4 device is well tolerated, and whether an increase in the ratio of 
risperidone to PABA influenced device performance. It had been previously noted from clinical 
data that PABA was leaving the device faster than risperidone, so by increasing PABA the 
longevity of the device might be increased. The devices were implanted for 182 days, and 
evaluated by plasma concentration over time, clinal observations, and post-explant tissue 
necropsy and histopathology. The release rates based on mass balance between the two 
RISP/PABA 1:2 groups was similar, 0.64mg/day and 0.72mg/day respectively for α2 and α4. The 
release rate was lower for the RISP/PABA 1:3 formulation in the α4 device, at 0.57mg/day. It can 
be concluded that drug release rate is approximately 10% higher for α4 devices compared with 
α2, and that RISP/PABA 1:2 in an α4 device is the best option for developing a long-acting, 
effective clinical product. RISP/PABA 1:3 resulted in a depressed output of risperidone, making it 
a suboptimal formulation.  
 
 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 29 of 101 
 
Table 2: Summary of Biocompatibility Studies with DLP-114 
 
Test 
Article 
Species or 
Strain 
ISO or USP 
Standard 
GLP 
Compliance  
Testing 
Facility 
Study 
Number 
Results 
Subcutaneous Implant Study, 13-week and 26-week 
DLP-114 
Implant 
New 
Zealand 
White 
Rabbits 
ISO 10993-
6 
Yes 
NAMSA TI249_826/S Well 
tolerated, little 
to no local 
tissue reaction 
DLP-114 
Implanter 
Tool 
ND 
ND 
ND 
ND 
ND 
ND 
Cytotoxicity 
DLP-114 
Implant 
L-929 
mouse 
fibroblast 
cells 
ISO 10993-
5 
Yes 
NAMSA V0014_130 
No observed 
cytotoxic 
effects 
DLP-114 
Implanter 
Tool 
L-929 
mouse 
fibroblast 
cells 
ISO 10993-
5 
Yes 
NAMSA V0014_130 
No observed 
cytotoxic 
effects 
Irritation Testing 
DLP-114 
Implant 
New 
Zealand 
White 
Rabbits 
ISO 10993-
10 
Yes 
NAMSA TI251_800 
Well tolerated 
in terms of 
intracutaneous 
irritability  
DLP-114 
Implanter 
Tool 
New 
Zealand 
White 
Rabbits 
ISO 10993-
10 
Yes 
NAMSA TI251_800 
Well tolerated 
in terms of 
intracutaneous 
irritability 
Pyrogen Testing 
DLP-114 
Implant 
New 
Zealand 
White 
Rabbits 
ISO 10993-
11 
Yes 
NAMSA TU010_807 
Nonpyrogenic 
DLP-114 
Implanter 
Tool 
New 
Zealand 
White 
Rabbits 
ISO 10993-
11 
Yes 
NAMSA TU010_807 
Nonpyrogenic 
Sensitization Testing 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 30 of 101 
 
DLP-114 
Implant 
Hartley 
Albino 
Guinea 
Pigs 
ISO 10993-
10 
Yes 
NAMSA TI261_300 
No delayed 
dermal 
contact 
sensitization 
DLP-114 
Implanter 
Tool 
Hartley 
Albino 
Guinea 
Pigs 
ISO 10993-
10 
Yes 
NAMSA TI261_300 
No delayed 
dermal 
contact 
sensitization 
Acute System Toxicity 
DLP-114 
Implant 
ND 
ND 
ND 
ND 
ND 
ND 
DLP-114 
Implanter 
Tool 
Mice 
(Mus 
musculus) 
ISO 10993-
11 
Yes 
NAMSA T0625_500 
No evidence 
of systemic 
toxicity 
Extractables and Leachables 
DLP-114 
Implant 
N/A 
ISO 10993-
18 
No 
NAMSA C0839_002/s Discovered 
substances do 
not pose a risk 
to a patient 
with lifetime 
exposure 
DLP-114 
Implanter 
Tool 
ND 
ND 
ND 
ND 
ND 
ND 
 
ISO Subcutaneous Implantation Study in Rabbits, 13 Week and 26 Week Implantation Report 
– Implant Device 
Testing was completed with seven New Zealand White Rabbits (Oryctolagus cuniculus), 
3-3.3kg at selection. Each animal was implanted with four DLP-114 devices using the Delpor 
implanter tool and four negative control articles. At 13 week, three rabbits were euthanized and 
the tissue surrounding the implant and control devices was examined. At 26 weeks, the remaining 
animals were euthanized and the tissue surrounding the implant and control devices was 
examined. Clinical observations were recorded throughout the duration of the study. The negative 
control article was USP high density polyethylene (HDPE). Tissues were macroscopically studied 
and scored from 0 (lowest) to 4 (highest) on encapsulation and irritation. 
No major clinical observations were reported. Two animals had small amounts of 
alopecia, two had reduced feces, and one had a dry, red, scaly lesion on the left rear foot for two 
days. Macroscopic observations showed no visible reaction at any test or control site in either the 
13-week group or the 26-week group. Microscopic observation caused a minimal or no reaction 
as compared to the negative control article in both the 13-week group and the 26-week group. See 
the NAMSA GLP report TI249_826/S  for detailed results.  
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 31 of 101 
 
Cytotoxicity Study Using the ISO Elution Method – Implant Device 
Testing was completed on the DLP-114 device prepared in single strength Minimum 
Essential Medium (IX MEM) at 37°C for 72 hours. The negative control, reagent control, and 
positive control were similarly extracted (see Delpor internal report RPT-1151 for more detail on 
extraction). Triplicate monolayers of L-929 mouse fibroblast cells were dosed with each extract 
and incubated at 37°C in the presence of 5% CO2 for 48 hours. Following incubation, the 
monolayers were examined microscopically for abnormal cell morphology and cellular 
degeneration.  
The test article extract showed no evidence of causing cell lysis or toxicity. The test article 
extract met the requirements of the test since the grade was less than a grade 2 (mild reactivity). 
See the NAMSA GLP report V0014_130 for detailed results.  
 
Cytotoxicity Study Using the ISO Elution Method – Implanter tool 
Testing was completed on the DLP-114 implanter tool prepared in single strength 
Minimum Essential Medium (IX MEM) at 37°C for 72 hours. The negative control, reagent 
control, and positive control were similarly extracted (see RPT-1151 for more detail on 
extraction). One test article (cannula and rod) were included in each preparation. Triplicate 
monolayers of L-929 mouse fibroblast cells were dosed with each extract and incubated at 37°C 
in the presence of 5% CO2 for 48 hours. Following incubation, the monolayers were examined 
microscopically for abnormal cell morphology and cellular degeneration.  
The test article extract showed no evidence of causing cell lysis or toxicity. The test article 
extract met the requirements of the test since the grade was less than a grade 2 (mild reactivity). 
See the NAMSA GLP report V0014_130 for detailed results. 
 
ISO Intracutaneous Study in Rabbits – Implant Device 
Test articles were extracted with 0.9% sodium chloride USP (SC) or sesame oil, NF (SO). 
Seven devices were cut in half and extracted with each extraction vehicle, continuously agitated 
for the extraction period. See RPT-1151 for more detail on extraction.  
Testing was completed with three New Zealand White Rabbits (Oryctolagus cuniculus), 
2.4-2.8kg at selection. A 0.2 mL dose of the appropriate test article extract was injected by the 
intracutaneous route into five separate sites on the right side of the back of each animal. Similarly, 
the corresponding control (the extraction vehicle alone) was injected on the left side of the back 
of each animal. Observations for erythema and edema were conducted at 24, 48, and 72 hours 
after injection. Reactions were scored on a 0 to 4 basis.  
All animals appeared normal throughout the study. See the NAMSA GLP report 
TI251_800 for detailed results. 
 
ISO Intracutaneous Study in Rabbits – Implanter Tool 
Test articles were extracted with 0.9% sodium chloride USP (SC) or sesame oil, NF (SO). 
Two articles (cannula and rod) were subdivided and extracted with each extraction vehicle, 
continuously agitated for the extraction period. See RPT-1151 for more detail on extraction. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 32 of 101 
 
Testing was completed with three New Zealand White Rabbits (Oryctolagus cuniculus), 
2.6-2.7kg at selection. A 0.2 mL dose of the appropriate test article extract was injected by the 
intracutaneous route into five separate sites on the right side of the back of each animal. Similarly, 
the corresponding control (the extraction vehicle alone) was injected on the left side of the back 
of each animal. Observations for erythema and edema were conducted at 24, 48, and 72 hours 
after injection. Reactions were scored on a 0 to 4 basis. 
All animals appeared normal throughout the study. See the NAMSA GLP report 
TI251_800 for detailed results. 
 
USP Rabbit Pyrogen Study, Material Mediated – Implant Device 
Test articles were extracted with sterile, nonpyrogenic 0.9% sodium chloride solution 
(SNPS). Sixty-four devices were cut in half and extracted with the extraction vehicle, with an 
extraction ratio of 900 cm2:150 mL, 790.2 cm2 of article amount, and 132 mL of vehicle. The 
extraction process was continuously agitated at 70° C for 24 hours. 
 
Testing was completed with three New Zealand White Rabbits (Oryctolagus cuniculus), 
3.4-3.9kg at selection. Temperatures were obtained rectally, with control temperatures recorded 
no more than 30 minutes prior to injection, and recordings taken at 30-minute intervals between 1 
and 3 hours after injection. Injection was delivered intravenously via the marginal ear vein with 
the test extract at 10 mL/kg of body weight.  
No single animal showed a temperature rise of 0.5° C or more above its baseline 
temperature. The total rise of the rabbits' temperature throughout the 3 hours was 0.4° C. See the 
NAMSA GLP report TU010_807 for detailed results. 
 
USP Rabbit Pyrogen Study, Material Mediated – Implanter Tool 
Test articles were extracted with sterile, nonpyrogenic 0.9% sodium chloride solution 
(SNPS). Sixteen test articles (cannula and rod) were subdivided and extracted with the extraction 
vehicle, with an extraction ratio of 900 cm2:150 mL, 920 cm2 of article amount, and 153 mL of 
vehicle. The extraction process was continuously agitated at 70° C for 24 hours. 
 
Testing was completed with three New Zealand White Rabbits (Oryctolagus cuniculus), 
3.5-3.7kg at selection. Temperatures were obtained rectally, with control temperatures recorded 
no more than 30 minutes prior to injection, and recordings taken at 30-minute intervals between 1 
and 3 hours after injection. Injection was delivered intravenously via the marginal ear vein with 
the test extract at 10 mL/kg of body weight.  
No single animal showed a temperature rise of 0.5° C or more above its baseline 
temperature. The total rise of the rabbits' temperature throughout the 3 hours was 0.2° C. See the 
NAMSA GLP report TU010_807 for detailed results. 
 
ISO Guinea Pig Maximization Sensitization Test – Implant Device 
Test articles were extracted with 0.9% sodium chloride USP (SC) or sesame oil, NF (SO). Seven 
test articles were included in each Induction I preparation and four test articles were included in 
each Induction II and Challenge preparation. Devices were cut in half and extracted with the 
extraction vehicle. The control is the extraction vehicle without the test article. See RPT-1151 for 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 33 of 101 
 
extraction details.  
Testing was completed with thirty Hartley Albino Guinea Pigs (Cavia porcellus), 302g to 
450g at selection. Ten animals were assigned to each test group (SC and SO extractions), and five 
were assigned to each control group (SC and SO vehicle alone). On the first day, during the 
Induction I phase, the animals were injected with their assigned extract or control. At day 6 
(Induction II), the animals were treated with a 10% SLS suspension to provoke mild 
inflammation, and 24 hours later were applied topically with a filter paper saturated in their 
assigned extracted or control. This was removed at 48 hours. 14 days after the completion of 
Induction II, cotton disks were saturated with extract or control, and applied to the animals, 
removed after 24 hours.  
 
Clinical observations were noted daily, observations for dermal reactions were conducted 
24 and 48 hours after challenge patch removal, and dermal reactions were scored from 0 (no 
visible change) to 3 (intense erythema and swelling).  
No major clinical observations were observed. Two animals had some significant self-
inducted trauma to the skin at Induction I injection sites, and were treated with an analgesic (see 
report). No evidence of sensitization was noted at 24 or 48 hours. The raw data can be found in 
appendix 2 of the RPT-1151.  See the NAMSA GLP report TI261_300 for detailed results. 
 
ISO Guinea Pig Maximization Sensitization Test – Implanter Tool 
Test articles were extracted with 0.9% sodium chloride USP (SC) or sesame oil, NF (SO). 
One test article (only the cannula and rod) was included in each preparation. Devices were 
subdivided and extracted with the extraction vehicle. The control is the extraction vehicle without 
the test article. See RPT-1151 for extraction details.  
Testing was completed with thirty Hartley Albino Guinea Pigs (Cavia porcellus), 301g to 
445g at selection. Ten animals were assigned to each test group (SC and SO extractions), and five 
were assigned to each control group (SC and SO vehicle alone). On the first day, during the 
Induction I phase, the animals were injected with their assigned extract or control. At day 6 
(Induction II), the animals were treated with a 10% SLS suspension to provoke mild 
inflammation, and 24 hours later were applied topically with a filter paper saturated in their 
assigned extracted or control. This was removed at 48 hours. 14 days after the completion of 
Induction II, cotton disks were saturated with extract or control, and applied to the animals, 
removed after 24 hours.  
 
Clinical observations were noted daily, observations for dermal reactions were conducted 
24 and 48 hours after challenge patch removal, and dermal reactions were scored from 0 (no 
visible change) to 3 (intense erythema and swelling).  
No major clinical observations were observed. No evidence of sensitization was noted at 
24 or 48 hours. The raw data can be found in appendix 2 of the report. See the NAMSA GLP 
report TI261_300 for detailed results. 
 
ISO Acute Systemic Toxicity Study in Mice – Implanter tool 
Test articles were extracted with 0.9% sodium chloride USP (SC) or sesame oil, NF (SO). 
Two test articles were included in each preparation. The control is the extraction vehicle without 
the test article. See RPT-1151 for extraction details.  

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 34 of 101 
 
Testing was completed with twenty mice (Mus musculus), 19g to 22g at selection. 10 
animals were used per extraction vehicle, with 5 assigned to be injected with extract and 5 to be 
injected with a control. The SC injections were intravenous, while the SO injections were 
intraperitoneal. Animals were observed for clinical reactions at 0, 4, 24, 48, and 72 hours. 
All animals were clinically normal throughout the study. Clinical observations can be 
found in the corresponding report. See the NAMSA GLP report T0625_500 for detailed results. 
 
Extractables and Leachables Chemical Characterization – Implant Device 
The test article, Delpor Device, was extracted (exhaustively) in Purified Water, Acidified 
Water, Isopropanol, and Hexane. The resulting extracts were analyzed by Gas Chromatography – 
Mass Spectrometry (GC-MS) for Semi-Volatile Organic Compounds (SVOC), Headspace – Gas 
Chromatography - Mass Spectrometry (HS-GC-MS) for Volatile Organic Compounds (VOC) and 
Ultra Performance Liquid Chromatography - Ultraviolet Spectrometry - Mass Spectrometry 
(UPLC-UV-MS) for Non-Volatile Organic Compounds (NVOC). The Purified Water (PW) test 
article extract was analyzed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) for 
ions and metals/elements. A breakdown of the extraction method can be seen in RPT-1151 and in 
NAMSA report C0839_002/s.   
Eleven characterized substances or groups of substances were identified as extractables 
from the DLP-114 implantable device at levels above the detection limit. An independent 
consultant (Gad Consulting Services) reviewed the results of the chemical characterization, and 
came to the determination that the substances listed should not present a potential risk to patients 
for any duration of implantation to include lifetime exposure. Please see Appendix A of RPT-
1151 for the full report on the safety of the results from extractables and leachables testing.  
 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 35 of 101 
 
 
7.4 Clinical Experience 
Delpor has completed a first-in-man ex-US PK/safety study of the DLP-114 device in Australia.  
This was a pilot 4-month trial of the 2 RISP/PABA 1:2 device in healthy subjects implanted in 
the arm with a single device using the clinical implanter tool.  After twelve subjects completed the 
study, an extension of the study (n=5) was added to bridge the alpha-2 RISP/PABA 1:2 and 
alpha-4 RISP/PABA 1:3.  
A total of seventeen subjects were dosed with the DLP-114 (12 with the α2 RISP/PABA 1:2 and 
5 with α4 RISP/PABA 1:3). PK analysis shows the average plasma levels are more variable in the 
first few weeks but settle into a steady state of about 6-7 ng/mL after Day 40 until the end of the 
dosing period at Day 123. 
The DLP-114 plasma values are in line with the exposure seen following a single 1 mg oral dose; 
the observed average Cmax is lower for the DLP-114-2 device relative to the 1.0 mg oral dose. 
Conversely, the Cmin is higher for the DLP-114-2 than for the oral dose. Mass balance analysis 
on devices removed from first 12 subjects who have completed the implant period indicate the 
average output is 1.01  0.10 mg/day. Plasma levels fall below the LLOQ within 12-24 hours 
after device removal.  
The insertion procedure was well-tolerated and incisions healed within a week or two.  No 
device-related serious AEs were reported.  Mild to moderate AEs at the implantation site included 
bruising, itching and pain in some subjects.  Risperidone effects included weight gain and 
prolactinemia. Punch biopsies of the implantation site in the first two subjects after device 
removal revealed no clinically significant inflammation.  One subject developed cellulitis two 
months into the implant phase of the study. Although the reaction was not rated as serious and 
responded to antibiotics, the PI felt the reaction was related to the device and to observe 
maximum caution in a volunteer study, the device was removed on Day 70.  It was noted for this 
participant, who had a relatively low BMI, that the implanted device formed a prominent bulge 
under the skin of the arm that the participant reported “touching” during the study.  It is believed 
that the lack of subcutaneous fat tissue and the relatively thin superficial fascia in the arm 
rendered the site problematic in as much as the layer between the skin and muscle was not 
sufficiently thick to comfortably accommodate the 5 mm OD device in this low BMI individual. 
This observation has prompted switching the implant site for this IND study to the abdomen 
where the subcutaneous fat/superficial fascia layer is generally thicker and the surface area 
available for implantation is greater.   
7.5 Risk/Benefit Assessment and Guidance for Investigators 
Eligible schizophrenia patients will be stable on 2-3 mg/day oral risperidone for at least 2 weeks, 
or will be stable on an antipsychotic other than oral risperidone (2-3 mg/day) but complete the 
conversion phase. Patients stable on 2-3 mg/day oral risperidone will be instructed to take oral 
risperidone (3 mg/day, unsupervised dosing) starting on Day -7. At the PI’s discretion, if patient 
has been screened, patient can commence oral dosing of risperidone (3 mg/day, unsupervised) as 
early as Day -10. Patients stable on an antipsychotic other than oral risperidone (2-3 mg/day) will 
be required to complete the conversion phase prior to beginning the unsupervised dosing on Day -
7. During the conversion phase, subjects will cross-titrate, at the PI’s discretion, from other 
antipsychotic(s) to oral risperidone therapy over a minimum of 2 weeks. Starting on Day -4, all 
patients will continue taking oral risperidone under supervision.  Implantation of DLP-114 will 
follow the oral risperidone treatment. Exposure following implantation of two DLP-114 is 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 36 of 101 
 
expected to be comparable to that of a 2-3 mg/day oral risperidone dose for 6 or 12 months.  Rat 
PK studies suggests exposure may be greater the first few weeks following implantation.  Also, 
following implantation in rats, a “burst” effect has been observed, with the highest plasma level 
observed 2 days following implantation (3 x higher than the steady state reached in the first 
week of implantation).  This initial burst is not seen in rabbits or human subjects. 
Dose dumping is considered unlikely. The total amount of risperidone loaded into each DLP-114 
device is ~360 mg in an alpha-4 device and ~435 mg in an alpha-7 device. The device has a 
robust design and functional testing regimen, and there have been no PK or mass balance signals 
suggestive of dose dumping in preclinical in vivo studies or clinical studies to date. Examination 
of devices removed from animals and human subjects after 4-12 months showed no evidence of in 
vivo membrane rupture or compromised reservoir or seals.  
Premarketing experience with oral risperidone includes eight reports of acute overdose with 
estimated doses ranging from 20 to 300 mg and no fatalities. In general, reported signs and 
symptoms resulting from an overdose were those resulting from an exaggeration of the drug's 
known pharmacological effects, i.e., drowsiness and sedation, tachycardia, hypotension and 
extrapyramidal symptoms. 
All components of the DLP-114 device that are directly exposed to tissues have been shown to be 
biocompatible. The mechanism of release from DLP-114 is passive diffusion. The device permits 
diffusion of water-soluble forms of risperidone across its membranes (driven by the concentration 
gradient created between the reservoir volume and the interstitial fluid), while retaining the 
insoluble suspension within the reservoir. The reservoir dimensions, housing material, finish and 
shape are modeled directly after Viadur, an FDA-approved osmotic implant. [1] The system is 
designed for subcutaneous implantation using a sterile disposable implanter tool and a minimally 
invasive procedure similar to that used for Viadur and Vantas [1, 2]. DLP-114 is implanted 
subcutaneously with local anesthesia in a quadrant of the abdomen. Implant removal is 
straightforward; the polished titanium surface has low tissue binding. 
Some local inflammation observed at the site of implantation in rats and more prominently in 
rabbits was only observed at histopathology and did not result in any visible swelling or erythema 
on the skin surface. Subcutaneous inflammation is common among injectable sustained release 
products with acidic formulations. These products are well-tolerated and such inflammation is 
reversible.  Histopathology conducted on two sentinel subjects in Delpor’s ex-US Phase 1 study 
showed no clinically significant inflammation following 4 months exposure.  
Potential adverse events that may be observed in this study due to implantation of the device 
include the following: 
 Pain at the site of implantation; 
 Skin irritation at the site of implantation; 
 Local tissue and blood vessel injuries; 
 Hematoma; 
 Local and/or systemic microbial infections; 
 Seroma. 
The distribution, metabolism, excretion, and systemic effects of risperidone are expected to be the 
same regardless of the route of administration (oral Risperdal, intramuscular Risperdal Consta or 
subcutaneous implant DLP-114). Several studies have reported risperidone-associated adverse 
effects such as hyperprolactinemia, weight gain, extrapyramidal symptoms, and other adverse 
effects in patients with schizophrenia. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 37 of 101 
 
Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were 
reported in patients (mean age 85 years; range 73-97) in trials of risperidone in elderly patients 
with dementia-related psychosis. These observations are the origin of the label warning of 
increased mortality among elderly patients taking risperidone. Elderly will be excluded from this 
clinical trial. 
Para-aminobenzoic acid (4-amino benzoic acid, PABA), is an excipient in the DLP-114 
drug/device product. PABA is an intermediate in the synthesis of folate by bacteria, plants, and 
fungi [3, 4] . Many bacteria, including those found in the human intestinal tract such as E. coli, 
generate PABA. PABA has been used as a component of sunscreens, and, given orally, as a 
diagnostic marker. It is a food additive. Clinical evidence suggest oral PABA provides benefit as 
an antifibrotic. Small amounts of PABA are found in cereal, eggs, milk and meats. Detectable 
amounts are normally present in human blood, spinal fluid, urine, and sweat [5]. The total amount 
of PABA loaded into a single DLP-114 implant is 240 mg for the α4 and 290 mg for the α7 
device. The α4 implant is expected to operate for at least 6 months whereas the α7 is designed to 
operate for at least one year, eluting risperidone at a fairly constant rate throughout the period. 
PABA release from the DLP-114 implant parallels that of risperidone, in an apparent 2:1 
stochiometric relationship. Assuming the PABA release is constant, exposure following 
implantation of a single DLP-114 implant is projected to be less than 1 mg/day. The projected 
daily exposure of PABA for each study patient is projected not to exceed that of one application 
of a 2% PABA sunscreen (3 mg becoming systemically bioavailable) or the consumption of seven 
servings of Brussel sprouts or peas (0.8 to 1.0 mg of total PABA). The exposure to the amount of 
PABA included in the DLP-114 is not expected to pose any significant safety risk to patients. 
PVP is used as a binder to aid tableting of the DLP-114 risperidone drug formulation. 
Approximately 32 mg of PVP40 is included in each DLP-114 α4 implant and 40 mg in each α7 
device. PVP is used in cosmetic formulations, food additives and pharmaceutics. PVP is approved 
as a food additive and clarifying agent for beverages and beer. PVP is added to wine up to 60ppm 
(21CFR173.55), so a 750 ml bottle of wine could contain up to 45 mg PVP. PVP is used as a 
binder to create tablets of a wide variety of oral drug products including acyclovir, ibuprofen, 
magaldrate, nystatin, phenytoin, trimethoprim, sulfonamides and antibiotics. PVP dissolved at a 
concentration of 3.5% in buffered saline has been used as a plasma substitute in emergency 
battlefield situations and surgery. A lower molecular weight PVP is included in intravenous 
formulations of antineoplastic drugs. The exposure to the amount of PVP included in the DLP-
114 is not expected to pose any significant safety risk to patients. 
A small amount of stearic acid is included in each DLP-114 device (~12 mg in the α4 device and 
~16 mg for the α7 device) as a lubricant to aid tableting of the formulation. Stearic acid is a 
ubiquitous fatty acid found in food and tissues. It is used in food with no limitation other than 
current good manufacturing practice. This ingredient is generally recognized as safe as a direct 
human food ingredient (21CFR 184.1090). The average intake of stearic acid is 5.7 g/day (8.1% 
of total fat) for women and 8.2 g/day (8.4% of total fat) for men, according to data from 
NHANES (National Health and Nutrition Examination Survey) 2001-2002 [6]. The exposure to 
the amount of stearic acid included in the DLP-114 is not expected to pose any significant safety 
risk to patients. 
The patients enrolled in this study are expected to benefit by maintaining plasma levels on the 
implant comparable to plasma levels achieved on their oral risperidone.   
The study is being conducted with schizophrenia patients who are stable on oral risperidone (2-3 
mg/day) for at least 2 weeks.  Preclinical and clinical evidence indicate the operating lifetime of 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 38 of 101 
 
the DLP-114 α4 will be at least 6 months and the α7 device will operate for at least 1 year, but 
this is not certain, the drug and/or the acid (which is needed to deploy the drug) may run out 
before 6 months for the alpha 4 device or 12 months for the alpha 7, and the patient may be 
underdosed, particularly in the later part of the dosing period. To safeguard an individual subject, 
stopping rules will include signs of impending relapse including:  
 Hospitalization due to worsening of schizophrenia; 
 Increase (worsening) of the PANSS of ≥30% from baseline. PANSST score confirmed at 
a second visit conducted within 1-7 days; 
 Clinically significant emergent or worsening suicidal, homicidal, or aggressive behavior; 
 A CGI-I Improvement (CGI-I) score of 6 (much worse) or 7 (very much worse) after start 
of study; 
 A need for additional antipsychotic treatment following the conversion phase, with the 
exception of protocol-permitted short-term add-on therapy (in the instance that the 
investigator believes that the subject is not experiencing a true exacerbation of 
schizophrenia, a supplemental antipsychotic may be used for a maximum of 14 days upon 
consultation with the medical monitor.) 
8 
STUDY OBJECTIVES 
8.1 Primary 
To evaluate the safety and tolerability of DLP-114: 
1) Determine the number and percent of patients experiencing a treatment-emergent adverse 
event; 
2) Evaluate the incidence of local site reactions; 
3) Assess the tolerability of implantation and explantation procedures. 
8.2 Secondary 
1) Measure the plasma concentration of risperidone and 9-OH risperidone and active moiety 
(risperidone + 9 OH risperidone) following repeated oral administrations. 
2) Measure the plasma concentration of risperidone and 9-OH risperidone and active moiety 
(risperidone + 9 OH risperidone) following switch from oral risperidone to subcutaneous 
implantation of two DLP-114 devices. 
3) Measure exploratory treatment outcomes using 2 psychiatric rating scales: the Clinical 
Global Impression (CGI-I) rating scale and the PANSS. 
4) Measure the amount of risperidone drug substance remaining in the DLP-114 reservoir 
following its removal, in order to estimate average daily output and duration. 
5) Determine average depth of device placement and any potential migration. 
 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 39 of 101 
 
9 
STUDY DESIGN  
9.1 Design Type and Description 
The study is an open-label, parallel group design aimed at assessing the safety and tolerability of 
DLP-114 and evaluating its utility in achieving a PK profile that is comparable to the marketed 
oral form of risperidone. 
Treatment of each patient will be conducted in four sequential periods (subjects will either enter 
the conversion phase or the unsupervised oral risperidone [3 mg/day] period) following Screening 
(Error! Reference source not found.) 
1. Conversion phase, if applicable (Cross-titration, at the PI’s discretion, from other 
antipsychotic(s) to oral risperidone therapy over a minimum of 2 weeks to achieve an oral 
risperidone dose of 3 mg by Day -14) - oral risperidone (3 mg/day) 
2. Unsupervised oral risperidone (3 mg/day) 
3. Supervised oral risperidone (3 mg/day)  
4. DLP-114 implant treatment with oral supplement (1 day) 
5. DLP-114 implant treatment; 
6. Follow-up. 
 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 40 of 101 
 
Figure 1: Flowchart of Study Design 
 
 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 41 of 101 
 
For a detailed description of the schedule of assessments refer to Section 14 (Study Conduct 
Schedules and Guidelines) and Appendix 1 (Overall Schedule of Assessments). 
For a detailed description of blood collection times (including time point windows) refer to 
Appendix 2 (Pharmacokinetic Sample Collection Schedule). 
 Unsupervised oral risperidone period (Day -7 to -5) 
Eligibility in the study requires that patients have been stable on 2-3 mg/day oral risperidone for 
at least 2 weeks.  Starting on Day -7, and as early as Day -10 at the PI’s discretion, patients who 
are currently on oral risperidone therapy (2-3 mg/day) will be instructed to take a dose of 3  
mg/day oral risperidone (unsupervised), daily through Study Day -5. 
 Oral risperidone conversion phase (minimum of 2 weeks prior to implant) 
Patients who are stable on an antipsychotic other than oral risperidone (2-3 mg/day) will cross-
titrate, at the PI’s discretion, from the other antipsychotic(s) to oral risperidone therapy over a 
minimum of 2 weeks. The objective of the oral conversion phase is for all subjects to achieve an 
oral risperidone dose of 3 mg by Day -14. 
 Supervised oral risperidone period (days -4 to 1) 
On Days -4, -3 and -2 all patients will be required to attend the clinical facility for outpatient 
visits to receive a dose of 3 mg/day oral risperidone (under the supervision of the clinical facility 
staff) and safety assessments. 
On the morning of Day -1 patients will be admitted and confined to the clinical facility overnight 
and for a period of 7 days. Following admission each patient will receive an additional supervised 
oral dose of risperidone (3 mg). PK samples will be collected pre-dose and at a number of time 
points following the fourth dose of oral risperidone. On the morning of Day 1 (immediately after 
the 24-hour PK sample, and immediately before the DLP-114 implantation), another oral dose 
will be administered (3 mg). 
 
 DLP-114 implant treatment period with oral supplement (Days 1 to 2) 
Patients will be assigned to Group 1 (DLP-114-α4) or Group 2 (DLP-114-α7).  On Day 1, 
following measurements of vital signs and collection of a pre-implantation blood samples (for 
PK), each Group 1 patient will be implanted with two DLP-114-α4 and each Group 2 patient with 
2 DLP-114-α7 devices. Following implantation, vital signs will be monitored, an ECG will be 
administered and safety laboratory tests will be performed. PK samples will be collected at 
several time points after DLP-114 implantation. A final oral dose of risperidone (3mg) will be 
administered 24 hours after implantation 
 
 DLP-114 implant treatment period (days 2-183 [± 7] for Gr 1, or days 2-365 [± 7] for Gr 
2) 
Patients will remain in the clinical facility for 72 hours post-implantation and will be discharged 
no later than Day 7. PK samples will be collected each day during the confinement period and on 
the day of discharge. 
Both groups will return to the clinical facility for outpatient visits once every week for safety 
assessments and PK sampling during the first 4 weeks after implantation (i.e., days 7, 14, and 28) 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 42 of 101 
 
and bi-weekly after that. Safety assessments will include vital signs, measurement of body 
weight, assessment of AEs, C-SSRS, review of con meds, and inspection of DLP-114 implant site 
at every visit. Other safety assessments (performed less frequently) will include a urine drug test, 
urine pregnancy test (female subjects only), safety lab test (blood and urine), ECG, CGI-I, 
PANSS, BARS, SAS, and AIMS (see Appendix 1. Overall Schedule of Assessments). 
An ultrasound will be conducted on day 14 and prior to implant removal in order to assess the 
depth of the implanted device and any possible vertical migration over time. 
Assessments may be performed more frequently than what’s stated in Appendix 1 based on the 
PI’s discretion. If a serious adverse event is observed the active moiety concentration will be 
measured to evaluate the possibility of dose-dumping. 
On the morning of Day 183 [± 7 days] (α4 Group 1) or Day 364 [± 7 days] (α7 Group 2) patients 
will attend the clinical facility for the removal of the DLP-114 implants. Vital signs and body 
weight will be obtained and a PK sample collected prior to the removal of the implant. Following 
the removal of the implant, vital signs will be monitored, safety laboratory tests will be conducted 
and a number of PK samples collected. Patients will be confined to the clinical facility for 2 
nights and will be discharged on the following day (Day 185 [± 7 days] for Group 1 or Day 366 
[± 7 days] for Group 2) following inspection of the implant site, a complete physical exam, safety 
review and PK sampling.  It may not be practical to schedule the exact explantation date at the 
time of patient enrollment (i.e., 6-12 months in advance).  As a result, the target date of 
explantation may be adjusted [± 7 days] in order to accommodate potential scheduling conflicts 
with the physician responsible for the explantation procedure.  In the event that the explantation 
date is adjusted, all the target dates following explantation will also be adjusted accordingly. 
 Follow-up and End of Study Visits (7 days [±1] after device removal) 
Patients will return to the clinical facility 3 days post implant removal (Day 186 for Group 1 and 
Day 367 for Group 2) for safety assessments and collection of PK samples.  
Each patient’s participation in this study will conclude on Day 190 (Group 1, α4) or Day 371 
Group 2, α7), 7 days post implant removal. Patients will attend the clinical facility for final safety 
assessments, including vital signs, an abbreviated physical examination, inspection of the 
implantation site, body weight, and AE assessment/review.  
9.2 Dose Administration Stopping Rules for an Individual Subject 
The PI and/or Sponsor may suspend or terminate dose administration upon any of the following 
events: 
 One occurrence of a Serious Adverse Event (SAE) assessed to be probably or possibly 
related to dosing with the investigational product; 
 Two or more severe Adverse Events (AEs) of the same character that are determined to be 
clinically significant by the investigator or sponsor and are assessed as probably or 
possibly related to dosing with the investigational product; 
 If four or more patients experience the same or similar moderate intensity AE which is 
possibly or probably related to the investigational product (or device), the sponsor and the 
investigator will review all available safety data and will recommend if dosing should 
continue. 
 Signs of impending relapse, including: 
o Hospitalization due to worsening of schizophrenia; 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 43 of 101 
 
o Increase (worsening) of the PANSS of ≥30% from baseline. PANSST score 
confirmed at a second visit conducted within 1-7 days; 
o Clinically significant emergent or worsening suicidal, homicidal, or aggressive 
behavior; 
o A CGI-I Improvement (CGI-I) score of 6 (much worse) or 7 (very much worse) 
after start of study; 
o A need for additional antipsychotic treatment 
9.3 Suspension or Termination of Study at the Investigational Site 
The sponsor reserves the right to terminate the investigational site or this clinical study at any 
time. Reasons for termination may include, but are not limited to, the following:  
 Unacceptable safety and tolerability; 
 The incidence or severity of AEs or SAEs that are observed in this study indicates a 
potential health hazard to patients; 
 Serious or persistent noncompliance by the investigator with the protocol, clinical research 
agreement, principles of the International Conference on Harmonisation (ICH) Good 
Clinical Practice (GCP), or applicable regulatory guidelines in conducting the study; 
 IRB decision to terminate or suspend approval for the investigator; 
 Investigator request to withdraw from participation; 
 Volunteer enrollment rate is unsatisfactory. 
9.4 Randomization and Blinding 
Patients will be assigned to one of two groups that will be dosed in parallel.  The dosing period 
for Group 1 is 183 (± 7) days and Group 2 364 (± 7) days. The study is open label. 
9.5 Endpoints 
 Safety Endpoints 
Safety endpoint evaluations will include the following: 
 Incidence and severity of AEs; 
 Local tolerance at the implantation site will be examined and scored for severity of visible 
signs of irritation/inflammation; 
 Tolerability of the implantation and explantation procedures; 
 Vital signs parameters; 
 Physical examination findings; 
 Electrocardiogram parameters; 
 Safety laboratory test parameters (serum chemistry, hematology, urinalysis). 
 C-SSRS 
 EPS Assessments (BARS, SAS, AIMS) 
 Pharmacokinetic Endpoints 
Evaluation of plasma concentrations of risperidone, 9-OH risperidone and active moiety 
(risperidone + 9 OH risperidone).  
PK parameters to be calculated for oral risperidone treatment period include: 
 Maximum concentration (Cmax); 
 Minimum concentration (Cmin) 
 Time to maximum concentration (Tmax); 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 44 of 101 
 
 Time to minimum concentration (Tmin) 
 terminal half-life (t1/2). 
PK parameters to be calculated for implant treatment period include:  
 Maximum concentration (Cmax); 
 Minimum concentration (Cmin) 
 Time to maximum concentration (Tmax); 
 Time to minimum concentration (Tmin); 
 Average concentration (Cave) 
 Exploratory Treatment Outcomes 
Exploratory treatment outcomes will be assessed using 2 psychiatric rating scales: the Clinical 
Global Impression (CGI-I) rating scale and the PANSS. 
 Device Endpoints 
 Implant spontaneous migration away from the initial subcutaneous implantation area 
during the implant treatment period. 
 Amount of unreleased drug substance remaining in the DLP-114 implant following its 
removal. 
 Depth of device placement 
9.6 Duration of the Study 
Group 1 
The study duration for each Group 1 patient will be up to 236 days (up to 278 with the conversion 
phase, if applicable). This includes the following: 
 Screening period (28 days) 
 Conversion phase (minimum 2 weeks) 
 Oral risperidone (3 mg/day, 3-6 days, unsupervised); 
 Oral risperidone (3 mg/day, 4 days, supervised); 
 DLP-114 α4 implant treatment (Group 1 183 days [± 7] days); 
 Follow-up (7 (± 1) days). 
Group 2 
The study duration for each Group 2 patient will be up to 417 days (up to 459 with the conversion 
phase, if applicable). This includes the following: 
 Screening period (28 days) 
 Conversion phase (minimum of 2 weeks) 
 Oral risperidone (3 mg/day, 3-6 days, unsupervised); 
 Oral risperidone (3 mg/day, 4 days, supervised); 
 DLP-114 α7 implant treatment (364 [± 7] days); 
 Follow-up (7 (± 1) days). 
If patients experience any clinically significant adverse events during the study, they may be 
required to remain in the clinical facility for further observation at the discretion of the 
investigator.  If a serious adverse event is observed the active moiety concentration will be 
measured to evaluate the possibility of dose-dumping. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 45 of 101 
 
9.7 Study Design Rationale  
This study design aims to establish the safety and tolerability of the DLP-114 implant and 
investigate the feasibility of switching from oral risperidone treatment to DLP-114 implant-based 
treatment.  
The open-label, parallel group design is intended to show comparable plasma risperidone PK 
when patients switch from 3 mg oral Risperdal® to either 1) DLP-114-α4 for 6 months (Group 1) 
or 2) DLP-114-α7 for one year (Group 2). 
Several safety assessments including vital signs, ECG, safety laboratory tests, regular inspections 
of the implantation site and AE monitoring are included in the design in order to minimize risk for 
the patients and obtain appropriate set of safety data to address the study primary objective.  
Given the primary Central Nervous System (CNS) effects of risperidone, caution should be used 
when this drug is taken in combination with other centrally acting drugs. In order to minimize the 
risk of CNS acting drug interactions, prescription/non-prescription drugs and drugs of abuse 
restrictions have been included with appropriate tests conducted throughout the study to ensure 
compliance. 
Risperidone has been classified in US FDA pregnancy category C: Animal reproduction studies 
have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in 
humans, but potential benefits may warrant use of the drug in pregnant women despite potential 
risks. Given this classification, this study will aim to mitigate against Exposure In Utero Events 
(EIU). Inclusion/exclusion criteria and study restrictions relating to contraception, as well as 
pregnancy tests have been included in the study design. 
10 PATIENT SELECTION 
10.1 Number of Patients 
Two groups of 12-15 schizophrenia patients (12-15 Group 1 and 12-15 Group 2) who have been 
stable on 2-3mg/day oral risperidone for at least 2 weeks, or who are stable on an antipsychotic 
other than oral risperidone (2-3 mg/day) but complete the conversion phase, will receive the DLP-
114 implants. Group 1 will receive 2 DLP-114-α4 devices and Group 2 will receive 2 DLP-114-
α7 devices.  
10.2 Inclusion Criteria 
To be eligible for enrolment, patients must meet the following criteria:  
1. Adult patients 18-70 years of age of both sexes diagnosed with schizophrenia or 
schizoaffective disorder according to DSM-V who have been stable on oral risperidone 
(2mg-3mg) for at least 2 weeks. 
    Note: Patients who are stable on an antipsychotic other than oral risperidone (2-3 
    mg/day) and complete the Conversion Phase may be enrolled. 
2. Patient (and/or a patient's authorized legal representative) has provided written informed 
consent 
3. Patient meets the following criteria: 
a. Outpatient status 
b. PANSS Total Score ≤ 80 at screening. 
c. A score of ≤ 4 on the following PANSS items: 
i. Conceptual disorganization 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 46 of 101 
 
ii. Suspiciousness 
iii. Hallucinatory behavior 
iv. Unusual thought content  
v. Hostility 
d. CGI-S ≤ 4 (moderately ill)\Lack of clinically significant suicidal ideation or 
behavior in investigator’s judgement; C-SSRS score type of 4-5 require evaluation 
by mental health professional to ensure patient safety in study 
4. Body Mass Index (BMI) within the range of 18.5 to 40.0 kg/m2 (inclusive); 
5. Ability to understand the nature and objectives of the trial, including risks and adverse 
events, and be able to read, review and sign the informed consent document prior to 
conduct of any study procedures; 
6. Willing and able to comply with the requirements of the study protocol; including 
willingness to visit the clinical facility for all outpatient visits and confinement periods; 
7. Have suitable venous access for blood sampling. 
8. Patient is assessed by the Investigator to be symptomatically stable with regard to pre-existing 
medical conditions as evidenced by medical history, non-clinically significant findings on 
physical examination, vital signs, clinical laboratory evaluations (hematology, serum 
chemistries, and urinalysis) or 12-lead electrocardiogram (ECG). Subjects may continue on 
their current prescribed medication regimens to control pre-existing medical and psychiatric 
conditions (other than schizophrenia) including the use of prescribed PRN medications. 
10.3 Exclusion Criteria  
Patients will be excluded from the study if any of the following criteria apply: 
1. PANSS score at baseline is ≥ 20% change from screening. 
2. Hospitalized or required acute crisis intervention for symptom exacerbation in the 60 days 
prior to admission as determined by the Investigator 
3. Patient has a history of suicide attempt in the last year, or in the opinion of the investigator 
is currently at imminent risk of suicide 
4. Patient experiencing acute depressive symptoms within the past 30 days, according to the 
Investigator's opinion, that required treatment with an antidepressant 
5. Has a current or recent (within 12 months) DSM-V diagnosis of moderate or severe 
substance use disorder (except for tobacco use disorder) or has a positive urine drug 
screen for prohibited substances at screening. 
6. Have impaired hepatic (ALT/AST >1.5 times higher than the upper limit of normal) or 
renal function (eGFR<50 mL/min) 
7. Previously defined hypersensitivity to Risperidone 
8. History of neuroleptic malignant syndrome (NMS) 
9. Electroconvulsive therapy within 6 months of admission 
10. Requires current use of agents that are strong inhibitors and inducers of cytochrome P450; 
11. Known hypersensitivity or allergy to lidocaine or any local anesthetic agent of the amide 
type (local anesthetic used during implant and explant procedures); 
12. Presence of clinically significant skin disorders (such as, but not limited to, skin cancer, 
psoriasis, eczema, or atopic dermatitis), evidence of recent sunburn, scar tissue, tattoo, 
open sore, body piercing or branding at the intended implantation site that would interfere 
with the implantation procedure or interfere with implant site assessments as determined 
by the investigator; 
13. History of clinically significant hypersensitivity or allergic reactions; 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 47 of 101 
 
14. Known allergy or hypersensitivity to PABA; 
15. Known allergy or hypersensitivity to parabens, local anesthetics of the ester type, and 
sulfa drugs including antibiotics and thiazide diuretics; 
16. Known hypersensitivity to titanium, implant materials or procedure; 
17. Administration of an investigational drug or device within 1 month prior to first dosing; 
18. Positive result for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibody, or 
HIV antibody; 
19. Pregnant or lactating patients. Positive pregnancy test; 
20. Positive drug test for Methamphetamines, Opiates, Cocaine, Phencyclidine, 
Benzodiazepines, Barbiturates, Methadone, Antidepressants and Amphetamines or 
positive alcohol test at screening or prior to first dose;  
21. Poor CYP2D6 metabolizer; 
22. History of skin picking or delusional parasitosis; 
23. Known history of abnormal scar formation or family history of keloid formation 
10.4 Patient Withdrawal Criteria 
Patients will be advised that they are free to withdraw from the study at any time for any reason 
or, if necessary, the investigator, or medically trained nominee, may discontinue a patient from 
the study, according to the following criteria, to protect the patient's health: 
1. The need to take medication which may interfere with study measurements; 
2. Intolerable/unacceptable adverse experiences; 
3. Major deviation of study protocol procedures; 
4. Non-compliance of patient with protocol; 
5. Patient unwilling to proceed and/or consent is withdrawn; or 
6. Withdrawal from the study if, in the investigator’s judgement, it is in the patient’s best 
interest. 
7. Signs of impending relapse 
The reasons for discontinuation will be recorded in the Case Report Form (CRF) and included in 
the final clinical study report, along with any adverse events and necessary medical treatment. 
Any patient who prematurely discontinued the study should undergo all Early Termination 
assessments/procedures (Appendix 1. Overall Schedule of Assessments).  
In the event that a patient is discontinued from the study due to an SAE, the investigator, or 
medically trained nominee, will evaluate the urgency of the event. If the situation warrants, the 
investigator, or medically trained nominee, will take appropriate diagnostic and therapeutic 
measures and make attempt to notify the sponsor medical representative. If the situation is not an 
immediate emergency, the investigator, or medically trained nominee, at the clinical study facility 
will attempt to contact the sponsor representative for consultation. No medical help, diagnosis, or 
advice will be withheld from the patient due to an inability to contact the sponsor. The patient will 
be encouraged to remain available for follow-up medical monitoring. The sponsor will be notified 
as soon as possible of any patient withdrawals. 
10.5 Patient Replacement 
Final confirmation of eligibility will be checked on dosing day. Patients who withdraw consent 
from the study prior to completion of the supervised oral risperidone treatment period may be 
replaced at the discretion of the investigator and following consultation with the sponsor.  

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 48 of 101 
 
Patients who withdraw consent from the study prior to completion of 
the first week of the implant treatment period for reasons other than 
occurrence of an SAE will be replaced. 
11 INVESTIGATIONAL PRODUCT 
11.1 Identification and Description 
Two versions of the DLP-114 device will be tested, the α4 device 
which is designed to operate for 6 months and the α7 device which is 
intended to operate for 1 year.  Both DLP-114 device versions are 
drug-device combination products consisting of a cylindrical 
titanium reservoir (5 mm in diameter and either 44 mm in length for 
the α4, or 50 mm in length for the α7) filled with a dry compressed 
mixture of risperidone aminobenzoate plus an excess of PABA. Standard Polyvinylidene 
difluoride (PVDF) membranes are positioned at each end of the reservoir (Figures 2A, 2B, and 
2C). The device is sealed in a vial under vacuum and activated by the end-user by introduction of 
sterile saline into the vial (similarly to the reconstitution of a lyophilized product). 
11.2 Investigational Substance 
Risperidone base powder will be received from the supplier (INKE, part of NEURAXPHARM 
GROUP, DMF 15682) by Hantel Technologies, an ISO 13485-compliant contract manufacturing 
organization.  Identity testing will be conducted.  
The drug substance is risperidone, a psychotropic agent belonging to the chemical class of 
benzisoxazole derivatives.  
 
Table 3. DLP-114 drug substance components, component amounts per device and projected 
daily exposure after implantation.  Alpha-4 / Alpha-7 
Component 
Total Loaded Equivalents 
(mg)1 
Projected Daily Exposure (mg)2 
Risperidone Base 
360/435 
1/1 
PABA 
240/290 
<1/<1 
PVP 40 
32/40 
<0.3/<0.3 
Stearic Acid 
12/16 
<0.1/<0.1 
1Mass loaded into individual units assuming a fill weight of 650 mg (alpha‐4) and 780 mg (alpha‐7) 
  
Figure 2A: Image of DLP-114 Titanium 
Implant  
Figure 2B: Section View of the DLP-114 Device 
 
 
Figure 2C: Relative Length 
of α4 and α7 devices 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 49 of 101 
 
2Normalized to dose elution rate of 1.0 mg/day projected for active 
 
 
The DLP-114 reservoir (Figure 2B) is filled with tablets made from a powder intermediate 
consisting of risperidone plus a 2x stochiometric excess of PABA. To aid in tableting the 
formulation, PVP40 and stearic acid are added.  The formulation components and projected daily 
exposure are shown in 
Table 3. The fill weight 
is 650 mg (alpha-4) and 
780 mg (alpha-7) 
11.3 Identification and 
Description of 
Reference 
Product 
Risperdal® (risperidone) 
will be used for the oral 
treatment period of the 
study.  
Risperdal® tablets are 
available in 0.25 mg 
(dark yellow), 0.5 mg 
(red-brown), 1 mg 
(white), 2 mg (orange). 
Risperdal® is 
manufactured by Janssen 
Pharmaceutica Products, 
LP. Additional 
information for Risperdal® is provided in the Risperdal® (risperidone) Product Information 
(Appendix 4 – Risperidal® (risperidone) Product Information). 
11.4 Description of the Investigational Device 
The clinical implant devices are designed under the Food and Drug Administration Design 
Controls (FDA 21 CFR 820.30) for human use. The device, shown as a section in Figure 2B, is a 
symmetrical cylinder 5 mm in diameter and either 44 mm in length for the DLP-114-α4 or 50 mm 
in length for the DLP-114-α7, with an internal drug compartment and diffusion ports at either 
end. 
The cylindrical titanium reservoir is filled with a dry compressed mixture of risperidone plus a 2-
fold molar excess of para-aminobenzoic acid (PABA) (Figure 2B). 
The mechanism of release from DLP-114 is passive diffusion, no mechanical parts or osmotic 
engines are needed; the entire reservoir volume is available for loading of the drug formulation. 
The only components directly exposed to tissues are the titanium reservoir and PVDF 
membranes, all have been shown to be biocompatible. 
 
Figure 3: Image of the DLP-114 Implanter Tool.  
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 50 of 101 
 
11.5 Implanter Tool 
The DLP-114 will be implanted using the Implanter Tool (Figure 3). This is a medical device used 
by medical professionals to implant the DLP-114 subcutaneously, where risperidone can be slowly 
released into the surrounding tissue. Both the DLP-114 device and the Implanter Tool are modeled 
after existing approved devices with respect to materials, size and shape. 
The Implanter Tool is manufactured by using well-characterized materials suitable for medical 
devices.  Detailed instructions on the correct handling and application of the Implanter Tool for 
implanting of DLP-114 are described in the IFU (see Appendix 5). 
 
11.6 Preparation, Labelling and Supply  
The investigational device and reference product to be administered will be labeled according to 
Good Manufacturing Practice for Medicinal Products. The detail on the labels will include, but 
not be limited to:  
 The notation- ‘Caution: New Drug--Limited by Federal (or United States) law to 
investigational use’; 
 Protocol number; 
 Investigator/site identification; 
 Trial patient number; 
 Name of sponsor; 
 Route of administration; 
 Batch number; 
 Retest date/expiry date; 
 Storage conditions. 
A sample of the label is attached under Appendix 6.  Study drug supplies will be stored securely 
at the Pharmacy. 
Investigational products (DLP-114) will be supplied to the Pharmacy by the sponsor (or delegate). 
The Risperdal® will be procured by the site. 
Detailed instructions for the preparation, labeling and supply of the investigational products are 
described in the study pharmacy manual. 
11.7 Storage, Handling and Accountability of Investigational and Reference Products 
 DLP-114 Storage and Handling 
Devices are stored and distributed to clinical sites sealed in lyophilization vials under vacuum, 
and should be stored at 2°-8°C. 
 Risperdal® Storage and Handling 
Risperdal® tablets should be stored at controlled room temperature 15°-25°C and protected from 
light and moisture. 
Additional information for Risperdal® is provided in the Risperdal® (risperidone) Product 
Information (Appendix 4 - Risperdal ® (risperidone) Product Information). 
 Accountability  

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 51 of 101 
 
Standard Operating Procedures will be followed for the receipt, handling and accountability of the 
investigational products.  
Investigational product must be stored in a locked area and protected from temperature extremes. 
Refer to the study pharmacy manual for additional storage requirements. 
The Pharmacy must ensure that deliveries of investigational products from the sponsor are 
correctly received by a responsible person, that all receipts of drug shipments are recorded on the 
appropriate Drug Accountability forms prepared by Pharmacy and that the products are stored in 
a secure area under recommended storage conditions. It is the responsibility of the investigator to 
ensure that the integrity of packaged investigational products not be jeopardized prior to 
dispensing.  
All materials supplied are for use only in this clinical study and should not be used for any other 
purpose. 
The Investigator, the site Pharmacist, or other personnel with authorized access to the 
investigational products will be responsible for ensuring that the study drug supplies used in the 
study are securely maintained as specified by the sponsor and in accordance with the applicable 
regulatory requirements. 
All study drugs will be dispensed in accordance with the investigator's prescription and it is the 
investigator's responsibility to ensure that an accurate record of “Investigational Product issued 
and returned” is maintained.  
The Pharmacy will dispense the investigational products to the clinical facility. Dispensing and 
supply will be verified by a second staff member. Dispensation will be recorded in the drug 
accountability records. The study pharmacy manual defines the procedures for dispensing. The 
clinical facility staff will administer the study medication only to patients included in this study 
following the procedures set out in this study protocol.  
Each patient will be given only the investigational product preparation carrying his/her study 
number. Study drug administration will be documented in the CRF and other study drug 
record(s). The investigator (or designated trained site staff) is responsible for assuring the 
retrieval of all left-over study supplies following administration to each patient. 
Any quality issue noticed with the receipt or use of an investigational product (packaging, 
appearance, pertaining documentation, labelling, expiry date, etc.) should be promptly notified to 
the sponsor, who will initiate recall procedures. 
Under no circumstances will the investigator supply any of the investigational products used in 
this study to a third party, allow the investigational product to be used other than as directed by 
this Clinical Trial Protocol, or dispose of investigational product in any other manner. 
12 ADMINISTRATION OF INVESTIGATIONAL PRODUCTS  
 Oral Risperidone Administration 
Risperidone tablets must be taken approximately 1 hour prior to any food consumption at 
approximately the same time each morning.  
On Day -7, or as early as Day -10 at the PI’s discretion, through Day -5, patients who are 
currently on oral risperidone therapy (2-3 mg/day) will self-administer 3 mg/day oral risperidone. 
During the conversion phase, subjects who are stable on an antipsychotic other than oral 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 52 of 101 
 
risperidone (2-3 mg/day) will be tapered off their current 
antipsychotic and titrated, at the PI’s discretion, to oral 
Risperidone 3 mg/day. Subjects will be dispensed a sufficient 
quantity of oral risperidone to last until the next scheduled study 
visit (+/- 3 days). Oral risperidone 1 mg to 3 mg/day will be 
self-administered at the investigator’s discretion in the 
conversion phase, either unsupervised or under the supervision 
of the investigator or other trained designee. Compliance with 
oral study medication will be monitored by tablet counts. 
Subjects who are noncompliant with oral study medication, in 
the Investigator’s judgment, are to be counselled on the 
importance of adhering to the daily administration schedule 
On Days -4 to -1, patient will self-administer 3 mg/day oral 
risperidone in the clinical facility under the supervision of the 
investigator or other trained designee.  
Each oral dose of risperidone will be administered with 
a full cup (approximately 240 mL) of non-carbonated 
room temperature water.  
Tablets must be swallowed whole and not chewed, 
divided, dissolved or crushed.  
Oral risperidone will be taken daily for 6 days as 
follows:  
 Day -4 to Day 2 (6 days) – 3 mg/day 
The penultimate dose of oral risperidone will be administered 
immediately prior to the DLP-114 implantation, and the final dose 
of oral risperidone, will be administered 24 hours after the DLP-114 
implantation.  The exact dates and times and dose of each study drug 
administration will be recorded in the CRF. 
 DLP-114 Implantation 
Each DLP-114 device is activated by the end-user on site. A detailed 
description of the hydration protocol is given in the DLP-114 
Instruction for Use. One precaution to ensure proper hydration is to 
inspect the vials following introduction of saline. A bubble is 
expected to form in the vial as shown in Figure 4A. Any larger 
bubble would indicate inadequate hydration and the device should 
not be used.  A bubble size indicator is included on the vial label 
which allows the user to check if the bubble size is acceptable (Figure 4B and 4C) 
 Subcutaneous implantation of two DLP-114 devices (either α4 or α7) will be performed by a 
qualified medical professional with experience conducting minor surgical procedures.  
The DLP-114 devices will be implanted in a quadrant of the abdomen 5 cm from midline and 5 
cm from the ribs using a sterile disposable implanter tool and local anesthesia in a minimally 
invasive procedure similar to that of other approved drug device products. Refer to the “Device 
Instructions for Use” for a guide on proper handling and application of the Implanter Tool for 
 
Figure 4B: The IFU provides guidance on 
how to check the hydration bubble size 
 
Figure 4A: Appearance of bubble 
in DLP-114 vial following proper 
hydration 
 
Figure 4C: Vial label with 
bubble indicator 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 53 of 101 
 
implanting of DLP-114. While the IFU contains detailed instructions, the implanting physician 
may deviate based on their clinical knowledge. If the physician does choose to deviate, they 
should record this on the implant-explant physician report. 
The device will remain implanted for either 183 (± 7) days (Group 1, α4) or 364 (± 7) days 
(Group 2, α7).  
Upon completion of the implant treatment period, the device will be removed by a qualified 
medical professional. 
13 CONCOMITANT MEDICATIONS AND OTHER RESTRICTIONS 
Compliance to these restrictions will be assessed throughout the duration of the study. 
13.1 Concomitant Medications 
Prior and Concomitant Therapy 
All non-study medications, including prescription, over-the-counter, or herbal therapies, used by 
the subject will be documented for the 45 days prior to Screening and throughout the study. The 
Investigator will determine if the prior/concomitant medication(s) affect the patient’s/subject’s 
eligibility to participate or continue to participate in the study. Any medication the patient takes 
between Screening and the end of the study, other than the study drug, is considered to be a 
concomitant medication. All concomitant medications must be recorded.  
Permitted, Prohibited, and Restricted Concomitant Medications 
Medications Prohibited During the Trial 
 Potent Cytochrome P450 2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine, 
cinacalcet, ritonavir) are prohibited during any Phase of the study. (NOTE: Any fluoxetine 
containing compound must be washed out for 42 days) 
 The use of investigational drugs will be restricted for at least 30 days (or 5-times the half-
life of the drug, if known and longer) prior to first study drug administration and 
throughout the study.  
 Mood stabilizers will be tapered and discontinued in the Screening Period at least 7 days 
prior to the Oral Treatment Period.  Mood stabilizers are not permitted during any the 
Phases of the study. 
 Nutritional supplements and nonprescription herbal preparations with central nervous 
system effects (e.g., St. John’s Wort, omega-3 fatty acids, kava extracts, gamma-
aminobutyric should be tapered and discontinued at least 14 days prior to the end of the 
Screening Period and are not permitted in any of the Phases of the study. 
Medications Restricted During the Trial 
 Benzodiazepines are allowed during all Phases of the study up to a maximum of 6 mg/day 
of lorazepam or equivalent. 
 Anticholinergics ≤ 4 mg/day benztropine or equivalent for EPS are permitted. 
 Propranolol (for akathisia or tremor) up to a maximum of 60 mg/day is permitted. 
 Subjects should discontinue any non-steroidal anti-inflammatory (NSAID) or aspirin-
containing medications one week prior to the Oral Treatment Period and one week prior to 
explantation. 
 Antipsychotics are allowed during the Screening period but are tapered off and converted 
to oral risperidone during the Conversion Phase. No antipsychotics, other than the 
Risperidone Implants are permitted following the conversion phase, except in certain 
cases. The certain cases include, where antipsychotics may be used during the study upon 
consultation with the medical monitor for maximum of 7 days throughout the study. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 54 of 101 
 
NOTE: In the instance that the investigator believes that the subject is not experiencing a true 
exacerbation of schizophrenia, a supplemental antipsychotic may be used for a maximum of 14 
days upon consultation with the medical monitor. 
 
Medications Permitted During the Trial 
 Non-benzodiazepine sleep aids are permitted  
 Non-sedating antihistamines (e.g., loratadine, cetirizine) are the treatment of choice for 
allergies. 
On a case-by-case basis, the Investigator is permitted to allow the use of some concomitant 
medications, for example, to treat an AE, as long as the Investigator determines that the 
medication will not affect the patient’s/subject’s safety or study integrity (e.g., topical 
medications). Whenever possible, the Investigator should obtain approval from the sponsor’s 
medical monitor prior to administering the medication.  
13.2 Contraception  
Female patients must use appropriate contraceptive methods from screening until the EOS visit. 
Male patient must use appropriate contraceptive methods and must not donate sperm following 
dosing with study drug until the EOS visit.  
Appropriate contraception is defined as using hormonal contraceptives or an intrauterine device 
combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or 
a condom. Also, total abstinence, in accordance with the lifestyle of the patient, is acceptable.  
13.3 Exercise 
Patients will be instructed to refrain from strenuous exercise and from participation in any contact 
sport activities for a period of 7 days following the implantation of DLP-114. 
13.4 Caffeine, and Alcohol 
The consumption of caffeine or alcohol are prohibited during periods of confinement to the 
clinical facility. 
14 STUDY PROCEDURES AND ASSESSMENTS 
14.1 Informed Consent 
The Patient Information and Consent Form (PICF) will be provided to the study volunteers at 
screening, prior to any study procedures being performed.  
14.2 Medical History 
Medical history and demographic data, including name, gender, age, race, Body Mass Index 
(BMI) will be recorded at screening. 
14.3 Safety Assessments  
This study will assess the safety and tolerability of DLP-114. Safety will be determined by 
evaluating physical examinations, vital signs, ECGs, clinical laboratory parameters, clinical 
ratings (e.g. C-SSRS), and adverse events. Local tolerance at the implantation site will be 
examined and scored for severity of visible signs of irritation/inflammation. If deemed necessary, 
additional safety measurements will be performed at the discretion of the investigator (or 
delegate). For details on the time points and frequency of all safety assessments, please see 
Appendix 1 (Overall Schedule of Assessments). 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 55 of 101 
 
 Physical Examination  
Complete physical examination performed at screening will include, at a minimum, assessment of 
the following systems: skin, head, ears, eyes, nose and throat, respiratory system, cardiovascular 
system, gastrointestinal system, neurological condition, blood and lymphatic systems, and the 
musculoskeletal system.  
Physical examination may be performed at various unscheduled time points if deemed necessary 
by the investigator. All physical examinations will be conducted by a licensed physician. 
 Implantation Site Inspection and Wound Care 
Subjects will receive written instructions that explain how to care for the surgical site after 
implant insertion and removal. Subjects should be informed about care of the implant site and 
implant site safety, educated about situations where they should seek medical attention, and 
queried about implant-related AEs.  
If an expulsion of an implant(s) occurs, and the subject appears to be compliant and wants to 
continue with the study, the current implant site will have the remaining implant removed and 
new implants (same dosage strength as original) will be implanted into another quadrant. If an 
expulsion occurs, the site is to contact the medical monitor to discuss if oral risperidone should be 
given to the patient prior to the following implantation. 
Implantation site inspection will be by visual and physical examination at each assessment visit. 
The physician will palpate the device and measure from the proximal end of the device to the 
incision to determine whether it has migrated by noting a change in distance from the incision site 
to the proximal end of the device. Healing of the incision will be monitored. Dermal reactions 
will be scored on a Skin Irritation Scoring System (Appendix 3, [1].) recommended for 
transdermal dosage forms that describes the amount of erythema, edema, and other features 
indicative of irritation. Any changes from baseline will be noted and captured as an AE. 
The DLP-114 implant should be implanted in a quadrant of the abdomen 5 cm from midline and 5 
cm below the ribs.  Any migration of the implant from this area, spontaneous expulsion on an 
implant(s), or other device-related event that does not qualify as an adverse event will be captured 
in the CRF on the Implant/Device Event form. 
 Electrocardiogram  
Single 12-lead ECG will be performed at selected time points (Appendix 1. Overall Schedule of 
Assessments). The patient should be in the semi-supine position for at least 10 minutes before the 
measurement is started and the following variables will be provided automatically: RR, PR, QRS, 
QT and QTcF intervals and pulse rate. In case of evident bad quality (muscle tremor) of the 
tracing, the ECG will be repeated. A description of the overall assessment (i.e. normal or 
abnormal plus reason) including clinical significance will be made and a copy of the trace placed 
with the source data. All ECGs should be obtained prior to vital signs and blood sampling when 
applicable. 
 Vital Signs  
Assessments will include systolic and diastolic blood pressure, pulse, body temperature, and 
respiratory rate. Patient should be resting in a semi-supine position for at least 5 minutes prior to 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 56 of 101 
 
and while vital signs measurements are obtained. Orthostatic blood pressure and pulse (after 
standing for 1, 3, and 5 minutes) will be performed at selected time-points (Appendix 1. Overall 
Schedule of Assessments).  
 Safety Laboratory Tests  
All safety laboratory analysis will be performed by the clinical site’s certified laboratory, using 
the laboratory’s normal ranges. The investigator must review the laboratory report, document this 
review, and record any clinically relevant changes occurring during the study in the AE section of 
the CRF. The following clinical laboratory safety tests will be performed (Appendix 1. Overall 
Schedule of Assessments): 
Hematology 
Leukocytes, erythrocytes, hemoglobin, hematocrit, thrombocytes; (partial automated 
differentiation): lymphocytes, monocytes, eosinophils, basophils, neutrophils. 
Serum Chemistry 
Sodium, potassium, calcium, phosphate, blood urea nitrogen (BUN), serum creatinine, glucose, 
lactic acid dehydrogenase (LDH), alanine transferase (ALT), aspartate transferase (AST), total 
bilirubin, alkaline phosphatase, gamma glutamyl transferase (GGT), total proteins, albumin and 
urates.  
Lipid profile analysis: total cholesterol, LDL, HDL, non-HDL and triglycerides. 
Patients will be required to fast for at least 4 hours prior to the initial Serum Chemistry time-point 
sample collection. 
Coagulation 
Prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin 
time (aPTT). 
Urinalysis 
Urine samples for urinalysis will be collected at specified time points. The following urinalysis 
parameters will be assessed: hemoglobin, urobilinogen, ketones, bilirubin, glucose, protein, 
nitrite, leukocytes, pH, specific gravity.  
 Viral Serology 
Blood will be collected for screening for hepatitis B surface antigen, hepatitis C antibody and 
HIV at the screening visit only. 
 Pregnancy Test 
Female patients will be screened for pregnancy: serum human chorionic gonadotropin (hCG) at 
the screening visit and urine hCG test at selected subsequent visits. If the urine hCG test is 
positive, pregnancy will be confirmed by a serum hCG test. In instances of a positive pregnancy 
result prior to dosing, the patient will be replaced. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 57 of 101 
 
 Alcohol and Drugs of Abuse Screen 
Alcohol breath test will be conducted at screening and prior to first dose. Urine drug test will 
include screen for: Methamphetamines, Opiates, Cocaine, Phencyclidine, Benzodiazepines, 
Barbiturates, Methadone, Tricyclic Antidepressants and Amphetamines. 
 Ultrasound 
On visit Day 14 an ultrasound will be taken of the implant site to determine depth of device 
placement.  The ultrasound will be repeated at the visit prior to implant removal to determine if 
the depth has changed. 
 C-SSRS, CGI-1 and PANSS,  
C-SSRS will be administered at screening and each patient visit (at least biweekly).  CGI-I will be 
administered at least monthly and PANSS approximately every 3 months.  PANSS will be 
administered more frequently if the CGI-I worsens.  
 Columbia-Suicide Severity Rating Scale (C-SSRS)  
The Columbia Suicide Severity Rating Scale (C-SSRS) [7] is a suicidal ideation rating 
scale. The scale identifies behaviors and thoughts that are associated with an increased 
risk of suicidal actions in the future. The C-SSRS Baseline/Screening version will be 
conducted at Screening and the Since Last Visit version will be used for all subsequent 
visits per the Schedule of Events.  
 Positive and Negative Syndrome Scale (PANSS) 
The Positive and Negative Syndrome Scale (PANSS) measures positive and negative 
syndromes associated with schizophrenia.  The scale consists of 33 items, 30 of which 
contribute to the PANSS Total Score (i.e., the sum of the seven P, or positive, items with 
the seven N, or negative, items with the 16 G, or general pathology, items).  The PANSS 
Total Score ranges from 30 – 210, with higher scores indicating greater pathology.   
Individual PANSS items are scored from 1 – 7, as follows: 
1 = Absent 
2 = Minimal 
3 = Mild 
4 = Moderate 
5 = Moderate/ Severe  
6 = Severe 
7 = Extreme 
The PANSS is administered at screening, baseline, and at additional timepoints noted in 
the Schedule of Assessments.  Of note, for study eligibility, the PANSS Total Score at 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 58 of 101 
 
screening must be ≤ 80 and the following five individual items must be ≤ 4: 
Conceptual Disorganization; Suspiciousness; Hallucinatory Behavior; Unusual Thought 
Content; and Hostility.  Additionally, there must not be a ≥ 20% change in the PANSS 
Total Score from screening to baseline. Finally, should the PANSS Total Score worsen 
by ≥30% compared to baseline at subsequent study visits (confirmed at an additional 
visit 1 – 7 days later), the subject may be exhibiting signs of relapse and may meet 
stopping criteria.    
 CGI-S and CGI-I 
Clinical Global Impression of Severity (CGI-S) will be rated based upon the severity of 
schizophrenia symptoms at screening and Day -1 during the oral treatment period, 
immediately prior to the implant + oral period. 
Severity of illness will be assessed based on following ratings: 
0 = Not assessed 
1 = Normal, not at all symptomatic 
2 = Minimally symptomatic 
3 = Mildly symptomatic 
4 = Moderately symptomatic 
5 = Markedly symptomatic 
6 = Severely symptomatic 
7 = Among the most extremely symptomatic subjects 
Drug response on symptoms of schizophrenia will be evaluated by the Clinical Global 
Impressions – Improvement (CGI-I). The CGI-I will be performed according to the 
timepoints in the Schedule of Assessments. The CGI-I scores range from 1 to 7: 
0 = not assessed (missing), 
1 = very much improved, 
2 = much improved, 
3 = minimally improved, 
4 = no change, 
5 = minimally worse, 
 
6 = much worse, 
 
7 = very much worse 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 59 of 101 
 
 EPS 
EPS symptoms will be monitored by the Barnes akathisia rating scale (BARS), Simpson–Angus 
scale (SAS) and abnormal involuntary movement scale (AIMS) at the beginning and at the end of 
the study, and may be performed more frequently based on symptoms at the PI's discretion. 
 Barnes Akasthisia Rating Scale (BARS) 
The Barnes Akasthisia Rating Scale (BARS) is a rating scale administered by physicians 
to assess the severity of drug-induced akathisia. This scale includes objective and 
subjective items such as the level of restlessness and global clinical assessment of 
akathisia. The BARS assessment will be performed at the time points indicated in the 
Schedule of Assessments. 
 Abnormal Involuntary Movements Scale (AIMS) 
The Abnormal Involuntary Movement Scale (AIMS) is a clinician-administered scale 
used to detect tardive dyskinesia (TD) and to follow the severity of a person’s TD over 
time. This 12-item anchored scale is clinician administered and scored.   
Items 1 through 10 are rated on a 5-point anchored scale: 
0=None 
1=Minimal, may be extreme normal  
2=Mild  
3=Moderate  
4-Severe 
Items 1 through 4 assess orofacial movements. 
Items 5 through 7 assess extremity and truncal dyskinesia. 
Items 8 through 10 assess global severity as judged by the examiner and the person’s 
awareness of the movements and the distress associated with them. 
Items 11 and 12 are yes-no questions concerning problems with teeth and/or dentures, 
because such problems can lead to a mistaken diagnosis of dyskinesia.  
A positive AIMS examination is a score of 2 in multiple movements or a score of 3 or 4 
in a single movement. The AIMS assessment will be performed at the time points 
indicated in the Schedule of Assessments. 
 Simpson-Angus Scale (SAS) 
The Simpson-Angus Scale (SAS) is a clinician-administered 10-item rating scale 
assessing the presence of drug-related extrapyramidal signs.  The 10 performance tasks 
are rated on a scale of 0 – 4 (normal to severe, as relevant to the task assessed).  The 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 60 of 101 
 
SAS will be performed at the timepoints indicated in the Schedule of Assessments.  
 Signs of impending relapse 
Any of the following signs would call for withdrawing the patient from the study: 
 Hospitalization due to worsening of schizophrenia; 
 Increase (worsening) of the PANSS of ≥30% from baseline. PANSST score confirmed at a 
second visit conducted within 1-7 days; 
 Clinically significant emergent or worsening suicidal, homicidal, or aggressive behavior; 
 A CGI-I Improvement (CGI-I) score of 6 (much worse) or 7 (very much worse) after start 
of study; 
 A need for additional antipsychotic treatment, with the exception of protocol permitted 
short-term add-on therapy. 
 Video Recording 
Four of the first subjects enrolled in the DLP-114-03 trial will have their implant and explant 
procedure video recorded and uploaded to a central repository. Approved video-recording 
equipment and standardized instructions for videotaping will be provided to the site. Each video 
recording will be identified by subject number, date, and time (including no personal identifying 
information). The camera will be positioned in such a way that the subjects’ face will not be 
included in the recording to protect the identity of the subject. Subjects who do not wish to be 
video recorded will be allowed to participate in the study. 
The purpose of video-recording a small number of implant and explant procedures is to: 
 Assess the performed procedure to ensure that it is aligned with the instructions provided 
in the training. 
 Identify and assess any observed misuses. Assessments will help drive product design 
changes and/or label changes to alleviate the risk’s severity or occurrence of the misuse. 
14.4 Pharmacokinetics 
Blood will be collected for the determination of plasma concentrations of risperidone, 9-OH 
risperidone and active moiety (risperidone + 9 OH risperidone) at the end of oral risperidone 
treatment, throughout the duration of the DLP-114 implant treatment and following removal of 
the DLP-114 implant. 
Clinic staff are required to take the blood samples for PK analysis at the scheduled time points 
within the time windows indicated (Appendix 2. Pharmacokinetic Sample Collection Schedule). 
Actual sampling dates and times are to be recorded in the CRF. 
If a patient discontinues prior to completion of the study, all of the PK data collected prior to 
discontinuation will be included in the PK analysis as appropriate.  
Three (3) mL of blood will be obtained for each PK sampling time point.  
The clinical site PK manual provides detailed instructions on sample processing, storage and 
shipping. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 61 of 101 
 
14.5 Total Blood Sample Volumes 
Blood samples for clinical labs and PK analysis will be collected from each patient throughout the 
study. An approximate total of no more than 250 mL of blood will be collected in Group 1 
patients and 500 mL in Group 2 patients. 
15 STUDY CONDUCT SCHEDULES AND GUIDELINES 
15.1 Screening, Selection and Consent 
Screening will be conducted within a period of 28 days prior to the start of the conversion phase 
or unsupervised oral dosing risperidone 3 mg/day. Informed consent will be obtained following 
provision of the PICF at screening and prior to any study procedures being performed. Patients 
will have to meet all eligibility criteria before being enrolled in the study.  
All screening laboratory test values (including viral) used for study eligibility assessment may be 
derived from patient medical history/record if obtained within a 28-day window prior to 
commencement of dosing for this study. 
Documentation of each patient’s fulfillment of the eligibility criteria (for all patients considered 
for the study and subsequently included or excluded) is to be completed by the investigator, or 
medically qualified delegate, including documentation that the patient has been stable on oral 
risperidone (2-3 mg/day) for at least 2 weeks, as well as if they have completed the conversion 
phase.  Documentation of screening failure details may be recorded using eligibility screening 
forms or a patient screen failure log.  Eligible patients will be assigned to either Group 1 or 2.  
The following assessments/procedures will be performed at the screening visit: 
 Informed consent; 
 Review of eligibility criteria; 
 Demographics; 
 Medical history; 
 Height; 
 Body weight; 
 Calculation of BMI; 
 Review of prior medications; 
 Physical examination (complete); 
 Viral serology; 
 Alcohol breath test; 
 Urine drug screen (drugs of abuse); 
 Serum hCG pregnancy test (females only); 
 Safety laboratory tests (blood); 
 Safety laboratory tests (urine); 
 12-lead ECG; 
 Vital signs (includes orthostatic blood pressure and pulse). 
 CYP2D6 Genotype (if subject provides documentation of a previous CYP2D6 result that 
shows the subject is not a poor metabolizer, it does not need to be repeated) 
 CGI-S 
 PANSS 
 C-SSRS 
 BARS  
 SAS  

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 62 of 101 
 
 AIMS 
 AE monitoring 
15.2 Clinical Conduct (Day -7 to Day -5): Groups 1 and 2 
Eligible patients who are currently on oral risperidone therapy (2-3 mg/day) will begin 
unsupervised dosing with oral risperidone 3 mg/day, starting on Day -7, or as early as Day -10 at 
PI’s discretion, through Day -5. Subjects will notify the site if the experience any AEs during the 
unsupervised oral dosing period.  
15.3 Clinical Conduct (Weekly Visits for a minimum of 2 weeks through Day -14): Groups 
1 and 2 
Eligible patients who are stable on an antipsychotic other than oral risperidone (2-3 mg/day) will 
be required to begin the conversion phase starting a minimum of 2 weeks prior to implant at the 
PI’s discretion. During weekly visits in the conversion phase, subjects will cross-titrate, at the PI’s 
discretion, from other antipsychotic(s) to oral risperidone therapy. The objective of the oral 
conversion phase is for all subjects to achieve an oral risperidone dose of 3 mg by Day -14.  
The following assessments will be performed at each weekly visit during the conversion phase: 
 Review of prior medications;  
 Vital signs and pulse (pre-dose); 
 C-SSRS; 
 AE monitoring; 
 Update/review of concomitant medications 
In addition, the Investigator will document details of the cross-titration that may occur during the 
conversion phase to bring about a stable transition from previous antipsychotic treatment(s) to 
oral risperidone 3 mg. The Investigator will also document the subject’s compliance with 
medications taken during the conversion phase. 
15.4 Clinical Conduct (Days -4 to 4): Groups 1 and 2 
 DAY -4 (outpatient visit) 
Eligible patients will present at the clinical facility on the morning of Day -4 (start of supervised 
dosing with oral risperidone 3 mg/day). On arrival at the clinical facility on Day -4, the 
investigator, or delegate, will meet with patients to explain all study procedures and encourage 
patients to ask any questions. All patients shall undergo a check-in procedure during which 
questions will be asked regarding protocol compliance and safety monitoring.  
The following assessments will be performed on each patient: 
 Review of eligibility criteria; 
 Body weight/height (includes calculation of BMI in the CRF); 
 Review of prior medications;  
 Vital signs and pulse (pre-dose); 
 Self- administration of investigational product under supervision at the clinical 
facility (3 mg oral risperidone); 
 C-SSRS 
 Urine hCG pregnancy test (females only) 
 AE monitoring; 
 Update/review of concomitant medications 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 63 of 101 
 
 DAY -3 and DAY -2 (outpatient visits) 
The following assessments/procedures will be performed:  
 Update/review of concomitant medications; 
 Self- administration of investigational product under supervision at the clinical 
facility (3 mg oral risperidone); 
 AE monitoring; 
 Vital signs; 
 DAY -1 (confinement to the clinical facility) 
Patients will be admitted to the clinical facility on Day -1. 
Patients will be confined to the clinical facility overnight (Day -1 to Day 4). If patients experience 
any clinically significant adverse events during this study period, they may be required to remain 
in the clinical facility for further observation at the discretion of the investigator. 
The following assessments/procedures will be performed on Day -1: 
 Update/review of concomitant medications; 
 Vital signs (pre-dose); 
 Blood sampling for PK (within 10 min prior to dose administration); 
 Self- administration of investigational product under supervision at the clinical 
facility (3 mg oral risperidone) – fourth dose of oral risperidone; oral dose should be 
given at least 25 hours prior to implantation to allow for the Day 1 pre-implant PK 
sample to be collected at least 30 minutes after the Day -1 24 hours post-dose PK 
sample 
 Blood sampling for PK at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (Appendix 2. 
Pharmacokinetic sample collection schedule); 
 AE monitoring. 
 Urine drug screen 
 Alcohol breath test 
 Urine hCG pregnancy test (females only) 
 Safety laboratory tests (blood); 
 Safety laboratory tests (urine); 
 12-lead ECG; 
 CGI-S 
 PANSS 
 C-SSRS 
 BARS 
 SAS 
 AIMS 
 DAY 1 (DLP-114 implantation day, confinement to the clinical facility) 
The following assessments/procedures will be performed: 
 Update/review of concomitant medications; 
 Vital signs - includes orthostatic blood pressure and pulse measurement (pre-
implantation); 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 64 of 101 
 
 Self- administration of investigational product under supervision at the clinical 
facility (3 mg oral risperidone) (1 hour (± 30 min) prior to DLP-114 implantation)– 
fifth dose of oral risperidone; 
 Blood sampling for PK (1 hour (± 30 min) prior to DLP-114 implantation) (Appendix 2. 
Pharmacokinetic sample collection schedule); 
 DLP-114 implantation (two implant devices per patient, Group 1 α4, Group 2 α7); 
 Provide wound care instructions; 
 AE monitoring; 
 Implantation site is inspected; 
 Vital signs (every hour for the first 8 hours post-implantation) - includes orthostatic blood 
pressure and pulse measurement at 4 hours post-dose; 
 12-lead ECG (4 hours post-implantation);  
 Blood sampling for PK at 1, 2, 3, 4, 6, 8 and 12 hours post-implantation (Appendix 2. 
Pharmacokinetic sample collection schedule). 
 C-SSRS 
 DAY 2 (confinement to the clinical facility) 
The following assessments/procedures will be performed: 
 Update/review of concomitant medications; 
 Approximately 24 hours post-implantation: 
o Vital signs; 
o Implantation site is inspected; 
o 12-lead ECG;  
o Self- administration of investigational product under supervision at the 
clinical facility (3 mg oral risperidone) – sixth (final) dose of oral risperidone; 
 Blood sampling for PK, 4 samples are collected at 24, 28, 32 and 36 hours following 
implantation of DLP-114 (Appendix 2. Pharmacokinetic sample collection schedule); 
 AE monitoring. 
 DAY 3 (confinement to the clinical facility) 
The following assessments/procedures will be performed: 
 Update/review of concomitant medications; 
 Vital signs - includes orthostatic blood pressure and pulse measurement (approximately 48 
hours post-implantation); 
 AE monitoring; 
 Implantation site is inspected; 
 Blood sampling for PK - 2 samples are collected at 48 and 52 hours following 
implantation of DLP-114 (Appendix 2. Pharmacokinetic sample collection schedule); 
 DAY 4-6 (confinement to the clinical facility) 
The following assessments/procedures will be performed: 
 Vital signs; 
 AE monitoring; 
 Update/review of concomitant medications; 
 Implantation site is inspected; 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 65 of 101 
 
 One blood sample for PK (Appendix 2. Pharmacokinetic sample collection schedule).  If 
a serious adverse event is observed the active moiety concentration will be measured to 
evaluate the possibility of dose-dumping; 
Participants may be discharged as early as Day 4 upon consultation with the study’s medical 
monitor. If patients are discharged prior to Day 7, the assessments listed in 15.4.8 shall be 
performed on the day of discharge, and the assessments listed in 15.5.1 shall be performed on Day 
7. Additionally, if patients are discharged prior to Day 7, the Day 4-6 assessments/procedures are 
unnecessary. 
 DAY 7 (discharge) 
The following assessments/procedures will be performed: 
 Body weight; 
 Update/review of concomitant medications; 
 Vital signs; 
 CGI-I; 
 C-SSRS; 
 Safety laboratory tests (blood) (excludes coagulation, and lipid profile); 
 Safety laboratory tests (urine); 
 AE monitoring; 
 Implantation site is inspected; 
 12-lead ECG; 
 One blood sample for PK (Appendix 2. Pharmacokinetic sample collection schedule); 
Patients will be given a study card and/or safety alert bracelet upon discharge from the clinic. 
15.5  Clinical Conduct (Days 14 to End of Study) – Group 1 
 DAYS 14, 21, 28, 42, 56, 70, 84, 98, 112, 126, 140, 154, and 168 (outpatient visits) 
After study Day 7, all outpatient visits during the implant treatment period may be performed 
within a window of ± 1 day. 
The following assessments/procedures will be performed at every outpatient visit: 
 Body weight 
 Vital signs; 
 C-SSRS 
 AE monitoring; 
 Implantation site is inspected;  
 One blood sample for PK (Appendix 2. Pharmacokinetic sample collection schedule).  If 
a serious adverse event is observed the active moiety concentration will be measured to 
evaluate the possibility of dose-dumping; 
 Update/review of concomitant medications. 
The following assessments/procedures will be performed on selected outpatient visits (see 
Appendix 1, Overall Schedule of Assessments; assessments may be performed more frequently 
based on symptoms at the PIs discretion): 
 Urine Drug Screen; 
 Urine hCG pregnancy test (females only); 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 66 of 101 
 
 Safety Lab Test (Blood); 
 Safety Lab Test (urine); 
 12-lead ECG; 
 CGI-I; 
 PANSS; 
 BARS; 
 SAS; 
 AIMS; 
 Ultrasound. 
 DAY 183 (± 7 days) (confinement to the clinical facility) 
The following assessments/procedures will be performed: 
 Body weight 
 Update/review of concomitant medications. 
 Urine Drug Screen  
 Urine hCG pregnancy test (females only) 
 12-lead ECG 
 Vital Signs 
 CGI-I 
 PANSS 
 C-SSRS 
 AE monitoring; 
 Implantation site monitored  
 Ultrasound (to measure if the implant has migrated vertically; implant should be located 
through palpation before removal) 
 DLP-114 implants are removed; 
 Blood sampling for PK at 1, 2, 3 
 , 4, 6, 8- and 12-hours following removal of the DLP-114 implant (Appendix 2. 
Pharmacokinetic sample collection schedule). 
 Safety laboratory tests (blood) (excludes coagulation, includes lipid profile) (4 hours 
following removal of the DLP-114 implant); 
 Safety laboratory tests (urine) (4 hours following removal of the DLP-114 implant); 
 Vital signs (every hour for the first 4 hours following removal of the DLP-114 implant); 
 12-lead ECG (4 hours following removal of the DLP-114 implant);  
 
 DAY 184 (confinement to the clinical facility ) 
On Day 184 (or 1-day post implant removal) the following assessments/procedures will be 
performed: 
 Update/review of concomitant medications. 
 Approximately 24 hours following removal of the DLP-114 implant: 
o Vital signs; 
o Implantation site is inspected;  
 AE monitoring; 
 One blood sample for PK (collected at 24 hours following removal of the implant) 
(Appendix 2. Pharmacokinetic sample collection schedule). 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 67 of 101 
 
 
 DAY 185 (confinement to the clinical facility ends) 
On Day 185 (or 2-days post implant removal) the following assessments/procedures will be 
performed: 
 Update/review of concomitant medications. 
 Approximately 48 hours following removal of the DLP-114 implant: 
o Vital signs; 
o Implantation site is inspected;  
 C-SSRS 
 AE monitoring; 
 One blood sample for PK (collected at 48 hours following removal of the implant) 
(Appendix 2. Pharmacokinetic sample collection schedule). 
 Resume oral administration of patient’s original dose (2-3 mg)  
 Physical examination (complete); 
 Confinement ends 
 
 DAY 186 (outpatient visit) 
On Day 186 (or 3 days post implant removal) the following assessments/procedures will be 
performed: 
 Vital signs; 
 C-SSRS 
 AE monitoring; 
 Implantation site is inspected;  
 One blood sample for PK (Appendix 2. Pharmacokinetic sample collection schedule).  If 
a serious adverse event is observed the active moiety concentration will be measured to 
evaluate the possibility of dose-dumping; 
 Update/review of concomitant medications. 
 
 DAY 190 (End of Study, outpatient visit) 
On Day 190 (or 7 days post implant removal) the following assessments/procedures will be 
performed as the End of Study Visit: 
 Body weight 
 AE monitoring/review; 
 Implantation site is inspected;  
 Urine hCG pregnancy test (females only); 
 C-SSRS 
 Vital signs; 
 Update/review of concomitant medications. 
15.6 Clinical Conduct (Days 14 to End of Study) – Group 2 
 DAYS 14, 21, 28, 42, 56, 70, 84, 98, 112, 126, 140, 154, 168, 182, 196, 210, 224, 238, 
252, 266, 280, 294, 308, 322, 336, and 350 (outpatient visits) 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 68 of 101 
 
After study Day 7, all outpatient visits during the implant treatment period may be performed 
within a window of ± 1 day. 
The following assessments/procedures will be performed at every outpatient visit: 
 Body weight 
 Vital signs; 
 C-SSRS 
 AE monitoring; 
 Implantation site is inspected;  
 One blood sample for PK (Appendix 2. Pharmacokinetic sample collection schedule).  If 
a serious adverse event is observed the active moiety concentration will be measured to 
evaluate the possibility of dose-dumping; 
 Update/review of concomitant medications. 
The following assessments/procedures will be performed on selected outpatient visits (see 
Appendix 1, Overall Schedule of Assessments; assessments may be performed more frequently 
based on symptoms at the PIs discretion): 
 Urine Drug Screen; 
 Urine hCG pregnancy test (females only); 
 Safety Lab Test (Blood); 
 Safety Lab Test (urine); 
 12-lead ECG; 
 CGI-I; 
 PANSS; 
 BARS; 
 SAS; 
 AIMS; 
 Ultrasound. 
 DAY 364 (± 7 days) (confinement to the clinical facility) 
The following assessments/procedures will be performed: 
 Body weight 
 Update/review of concomitant medications. 
 Urine Drug Screen  
 Urine hCG pregnancy test (females only) 
 12-lead ECG 
 Vital Signs 
 CGI-I 
 PANSS 
 C-SSRS 
 AE monitoring; 
 Implantation site monitored  
 Ultrasound (to measure if the implant has migrated vertically; implant should be located 
through palpation before removal) 
 DLP-114 implants are removed; 
 Blood sampling for PK at 1, 2, 3, 4, 6, 8- and 12-hours following removal of the DLP-114 
implant (Appendix 2. Pharmacokinetic sample collection schedule). 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 69 of 101 
 
 Safety laboratory tests (blood) (excludes coagulation, includes lipid profile) (4 hours 
following removal of the DLP-114 implant); 
 Safety laboratory tests (urine) (4 hours following removal of the DLP-114 implant); 
 Vital signs (every hour for the first 4 hours following removal of the DLP-114 implant); 
 12-lead ECG (4 hours following removal of the DLP-114 implant);  
 
 DAY 365 (confinement to the clinical facility) 
On Day 365 (or 1-day post implant removal) the following assessments/procedures will be 
performed: 
 Update/review of concomitant medications. 
 Approximately 24 hours following removal of the DLP-114 implant: 
o Vital signs; 
o Implantation site is inspected;  
 AE monitoring; 
 One blood sample for PK (collected at 24 hours following removal of the implant) 
(Appendix 2. Pharmacokinetic sample collection schedule). 
 
 DAY 366 (confinement to the clinical facility ends) 
On Day 366 (or 2-days post implant removal) the following assessments/procedures will be 
performed: 
 Update/review of concomitant medications. 
 C-SSRS 
 Approximately 48 hours following removal of the DLP-114 implant: 
o Vital signs; 
o Implantation site is inspected;  
 AE monitoring; 
 One blood sample for PK (collected at 48 hours following removal of the implant) 
(Appendix 2. Pharmacokinetic sample collection schedule). 
 Resume oral administration of patient’s original dose (2-3 mg)  
 Physical examination (complete); 
 Confinement ends 
 
 DAY 367 (outpatient visit) 
On Day 367 (or 3 days post implant removal) the following assessments/procedures will be 
performed: 
 Vital signs; 
 C-SSRS 
 AE monitoring; 
 Implantation site is inspected;  
 One blood sample for PK (Appendix 2. Pharmacokinetic sample collection schedule).  If 
a serious adverse event is observed the active moiety concentration will be measured to 
evaluate the possibility of dose-dumping; 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 70 of 101 
 
 Update/review of concomitant medications. 
 
 DAY 371 (End of Study, outpatient visit) 
On Day 371 (or 7 days post implant removal) the following assessments/procedures will be 
performed as the End of Study Visit: 
 Body weight 
 AE monitoring/review; 
 Implantation site is inspected;  
 Urine hCG pregnancy test (females only); 
 C-SSRS 
 Vital signs; 
 Update/review of concomitant medications. 
 
15.7 Early Termination Procedures 
The following assessments/procedures will be performed on a patient at an early termination visit 
to the clinical facility: 
If early termination occurs during the DLP-114 implant treatment period: 
 One blood sample for PK prior to removal. 
 Implantation site is inspected, and the DLP-114 implant is removed; 
 Update/review of concomitant medications; 
 Physical examination; 
 Urine hCG pregnancy test (females only); 
 Safety laboratory tests (blood) (excludes coagulation, includes lipid profile) (4 hours 
following removal of the DLP-114 implant); 
 Safety laboratory tests (urine) (4 hours following removal of the DLP-114 implant); 
 Vital signs (every hour for the first 4 hours following removal of the DLP-114 implant); 
 12-lead ECG (4 hours following removal of the DLP-114 implant);  
 AE review; 
 CGI-I 
 PANSS 
 C-SSRS 
 Implantation site monitored  
 BARS 
 SAS 
 AIMS 
Patients will be requested to return to the clinic for a follow up visit 6 (±3) days following the 
removal of the implant, for implant site inspection and AE assessment. 
If early termination occurs during the oral risperidone treatment period: 
 Update/review of concomitant medications; 
 Urine hCG pregnancy test (females only); 
 Safety laboratory tests (blood) (excludes coagulation and lipid profile); 
 Safety laboratory tests (urine); 
 12-lead ECG;  

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 71 of 101 
 
 Vital signs; 
 AE review. 
15.8 Timing of Treatments and Procedures 
Clinical staff are required to perform assessments at the nominated time-points within the time 
windows indicated in this protocol. Actual times of procedures for each patient may vary 
depending on scheduling and will be recorded in the CRF. In the event of multiple procedures 
scheduled at the same time, the order will be: 
1. 12-lead ECG; 
2. Vital signs; 
3. Blood sampling for PK; 
4. Blood sampling for safety laboratory tests; 
5. Assessment of implantation site. 
16 ASSESSMENT AND MANAGEMENT OF ADVERSE EVENTS 
16.1 Adverse Event Definitions 
An Adverse Event (AE) is any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational/experimental) product, whether or not 
related to this product.  
A Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose: 
 Results in death; 
 Is life-threatening (the term ‘life-threatening’ in the definition of ‘serious’ refers to an 
event/reaction in which the patient was at risk of death at the time of the event/reaction; it 
does not refer to an event/reaction which hypothetically might have caused death, if it 
were more severe); 
 Requires inpatient hospitalization or prolongation of an existing hospitalization (only 
hospitalizations that are longer than expected based on Investigator judgment, will be 
considered prolonged hospitalizations); 
 Results in persistent or significant disability/incapacity (an AE that results in a substantial 
disruption of a person’s ability to conduct normal life functions); 
 Is a congenital anomaly/birth defect (a congenital anomaly/birth defect that occurs in the 
offspring of a patient exposed to the investigational product); 
 Is a medically important event or reaction (an AE that may not result in death, be life-
threatening, or require hospitalization may be considered an SAE when, based upon 
appropriate medical judgment, the event may jeopardize the patient and may require 
medical or surgical intervention to prevent one of the outcomes listed above). 
Medical and scientific judgment should be exercised in deciding whether other situations, should 
be considered serious such as important medical events that may not be immediately life 
threatening or result in death or hospitalization but might jeopardize the patient or might require 
medical or surgical intervention to prevent one of the other outcomes listed in the above 
definition. These should also be considered serious. Examples of such events are intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or drug 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 72 of 101 
 
abuse. 
A Suspected Unexpected Serious Adverse Reaction (SUSAR): is an AE that is believed to be 
related to the investigational product and is both unexpected and serious. An adverse event or 
suspected adverse reaction is considered "unexpected" if it is not listed in the investigator 
brochure or is not listed at the specificity or severity that has been observed; or, if an investigator 
brochure is not required or available, is not consistent with the risk information described in the 
general investigational plan or elsewhere in the current application. For example, under this 
definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the investigator 
brochure referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) if 
the investigator brochure listed only cerebral vascular accidents. "Unexpected," as used in this 
definition, also refers to adverse events or suspected adverse reactions that are mentioned in the 
investigator brochure as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug, but are not specifically mentioned as occurring with the 
particular drug under investigation. 
Abnormal laboratory findings (e.g. clinical chemistry, hematology, coagulation and urinalysis) 
or other abnormal assessments (e.g., ECG tracings for safety assessment, vital signs) that are 
judged by the investigator as clinically significant will be recorded as AEs or SAEs if they meet 
the definitions stated in above. Clinically significant abnormal laboratory findings or other 
abnormal assessments that are detected during the study or are present at baseline and 
significantly worsen following the start of the study will be reported as AEs or SAEs. The 
investigator will exercise his or her medical and scientific judgment in deciding whether an 
abnormal laboratory finding or other abnormal assessment is clinically significant. 
An Implant/Device Event (IDE) is defined as an expulsion, migration, or other device-related 
event that does not qualify as an adverse event. The evaluating physician will make the 
determination as to the root cause of the event and classify it accordingly. See section 14.3.2 for 
instructions on expulsion procedure.  
16.2 Evaluating AE and SAE 
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study. The assessment will be based on the investigator’s clinical judgment. The intensity of each 
AE and SAE will be graded using the most current version of the Common Terminology Criteria 
for Adverse Events (CTCAE) 5-point scale: 
 Mild (Grade I): Asymptomatic or mild symptoms: clinical or diagnostic observations 
only; intervention not indicated; 
 Moderate (Grade II): Minimal, local or non-invasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL); 
 Severe (Grade III): Severe or medically significant but not immediately life-threatening: 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL; 
 Life-threatening (Grade IV): Life-threatening consequences; urgent intervention 
indicated; 
 Death (Grade V): Death related to the event. 
If an AE has multiple aspects, the aspect with the highest severity will be graded. 
The term severe is a measure of severity. Thus, a severe AE is not necessarily serious. For 
example, itching for several days may be rated as severe, but may not be clinically serious. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 73 of 101 
 
 Assessment of Causality 
The investigator will make an assessment as to the relationship between investigational product 
effect and the occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine whether or not the AE/SAE is causally related to the investigational drug product. 
Alternative causes, such as natural history of the underlying diseases, concomitant therapy, other 
risk factors, and the temporal relationship of the event to the investigational product will be 
considered and investigated. The investigator will also consult the Investigator’s Brochure in the 
determination of his/her assessment. 
The causal relationship of the investigational product to an AE will be rated according to the 
following 5-point scale:  
 Unrelated: Clearly and incontrovertibly due only to extraneous causes, and does not meet 
criteria listed under unlikely, possible or probable; 
 Unlikely: Does not follow a reasonable temporal sequence from administration; may have 
been produced by the patient’s clinical state or by environmental factors or other therapies 
administered; 
 Possibly: Follows a reasonable temporal sequence from administration; may have been 
produced by the patient’s clinical state or by environmental factors or other therapies 
administered; 
 Probably: Clear temporal association with improvement on cessation of investigational 
product or reduction in dose. Reappears upon re-challenge or follows a known pattern of 
response to the investigational product; 
 Definitely: An AE that cannot be reasonably explained by an alternative explanation, e.g., 
concomitant drug(s), concomitant disease(s). The relationship in time is very suggestive. 
There may be situations when an SAE has occurred and the investigator has minimal information 
to include in the initial report to the sponsor. However, it is very important that the investigator 
always make an assessment of causality for every event prior to transmission of the SAE form to 
the sponsor. The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE form and the CRF accordingly. The causality assessment is one 
of the criteria used when determining regulatory reporting requirements. 
 Action Taken and Outcome 
For all AEs reported, the actions taken and outcomes will be specified. 
Actions taken may include any of the following: 
 No action; 
 Medication required; 
 Tests required; 
 Hospitalization required (or prolonged); 
 Investigational product administration interrupted/withdrawn; 
 Other (specify). 
The following terms and definitions are used in assessing the final outcome of an AE:  
 Recovered - The patient has fully recovered, or by medical or surgical treatment the 
condition has returned to the level observed at the first trial-related activity after the 
patient signed the informed consent. 
 Recovering - The condition is improving and the patient is expected to recover from the 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 74 of 101 
 
event. 
 Recovered with sequelae - The patient has recovered from the condition, but with lasting 
effect due to a disease, injury, treatment or procedure. If a sequelae meets an SAE 
criterion, the AE must be reported as an SAE. 
 Not recovered - The condition of the patient has not improved and the symptoms are 
unchanged, or the outcome is not known at the time of reporting. 
 Fatal - This term is only applicable if the patient died from a condition related to the 
reported AE. Outcomes of other reported AEs in a patient before he/she died should be 
assessed as “recovered”, “recovering”, “recovered with sequelae” or “not recovered”. An 
AE with fatal outcome must be reported as an SAE. 
 Unknown - This term is only applicable if the patient is lost to follow-up. 
16.3 Procedures and Time Period for Detecting Adverse Events 
The investigator or designee is responsible for detection, recording and reporting of events that 
meet the criteria and definition of AE.  
As a consistent method of soliciting AE, the patient shall be asked a non-leading question such as: 
"How do you feel?”. 
Any pre-existing conditions or signs and/or symptoms present in a patient prior to the start of the 
study (i.e., before informed consent) should be recorded as Medical/Surgical History. In addition, 
any change in health status, which is reported after informed consent is obtained but prior to 
starting study treatment will be documented as Medical/Surgical History. 
Any medical occurrence reported or observed after the informed consent form is signed until 
completion of the last study related procedure (includes follow-up for safety assessments) will be 
recorded as an AE.  
Any AEs already documented at a previous assessment and designated as ongoing, should be 
reviewed at subsequent assessments as necessary. If these have resolved, this should be 
documented. 
A post-study AE is defined as any event that occurs outside of the nominal AE study detection 
period. Investigators are not obligated to actively seek AE in former study patients. However, if 
the investigator learns of any SAE, including a death, at any time after a patient has completed the 
study and he/she considers the event reasonably related to the investigational product, the 
investigator will promptly notify the sponsor.  
Patients must be provided with a “study card” indicating the name of the investigational product, 
the study number, the investigator’s name, a 24-hour emergency contact number, and, if 
applicable, excluded concomitant medications. Patients will also be offered a safety alert bracelet 
bearing the same information, if desired, instead of or in addition to the study card. The study 
card and/or bracelet will be provided upon discharge from the clinic following the implant device 
administration. 
16.4 Recording of AEs and SAEs 
All AEs, regardless of seriousness, severity, or presumed relationship to study treatment, must be 
recorded using medical terminology in the CRF and/or other sources. Whenever possible, 
diagnoses should be given when signs and symptoms are due to a common etiology (e.g., cough, 
runny nose, sneezing, sore throat, and head congestion should be reported as “upper respiratory 
infection”). Investigators must record in the CRF their opinion concerning the relationship of the 
adverse event to study therapy. All measures required for adverse event management must be 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 75 of 101 
 
recorded in the CRF and reported according to sponsor instructions. 
16.5 Reporting of SAEs and SUSARs 
In accordance with ICH guidelines for GCP, a copy of the written report of any SAEs should 
promptly be sent to the study sponsor. The investigator must notify the study sponsor (and the 
designated study safety officer) within 24 hours of becoming aware of the occurrence of an SAE.  
Table 4. Contact details for transmission of SAE reporting forms to the sponsor and sponsor 
designated safety officer. 
Sponsor Contact 
Designated Safety Officer 
Dr. Frank Martin  
Chief Science Officer 
Delpor, Inc 
150 Hill Drive, Suite 25 
Brisbane, CA 94005 
Lawrence Frederick Blob, MD 
Chief Medical Officer 
CRC 
200 Central Avenue, Suite 1230 
Saint Petersburg, FL 33701 
Email: frank.martin@delpor.com 
lblob@cogres.com 
Fax: (415) 480 6871 
Fax: (727) 897-9009 
Phone: (415) 480 6872 
Office: (727) 897-9000 
Mobile: (650) 759 0155 
Mobile: (410) 262-1908 
Information regarding SAEs will be transmitted to the sponsor using a SAE Form (or Medical 
Device Incident Report form) as described in the study Safety Reporting Plan. The SAE Form 
must be completed and signed by a member of the investigational staff, and transmitted to the 
sponsor (and designated study safety officer) within 24 hours (Table 4). The initial and follow-up 
reports of an SAE should be made by facsimile (fax) or e-mail. 
The investigator must report SAEs to the appropriate IEC/IRB that approved the protocol unless 
otherwise required and documented by the IEC/IRB. 
It is the responsibility of the sponsor to determine whether a reported SAE fits the classification 
of a SUSAR. The investigator’s opinion regarding the assessment of expectedness (if provided) 
and causality will be taken into account in the sponsor’s determination of the SAE as a SUSAR. 
The causality assessment given by the investigator cannot be downgraded by the sponsor. 
SAEs (and SUSARs) will be reported to competent authorities in accordance with national 
requirements. The sponsor assumes responsibility for appropriate reporting of SAEs (and 
SUSARs) to the regulatory authorities.  
16.6 Follow-up of AE and SAE 
After the initial AE/SAE report, the investigator is required to proactively follow each patient and 
provide further information to the sponsor on the patient’s condition. 
All AEs and SAEs documented at a previous visit/contact and are designated as ongoing, will be 
reviewed at subsequent visits/contacts. SAEs that have not resolved by the end of the study, or 
that have not resolved upon discontinuation of the patient’s participation in the study, must be 
followed until any of the following occurs: 
 The event resolves; 
 The event stabilizes; 
 The event returns to Baseline, if a Baseline value is available; 
 The event can be attributed to agents other than the investigational product or to factors 
unrelated to study conduct; 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 76 of 101 
 
 It becomes unlikely that any additional information can be obtained (patient or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration 
of due diligence with follow-up efforts). 
The investigator will ensure that SAE follow-up includes any supplemental investigations as may 
be indicated to elucidate the nature and/or causality of the event. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals. 
The sponsor may request that the investigator perform or arrange for the conduct of supplemental 
measurements and/or evaluations to elucidate as fully as possible the nature and/or causality of 
the SAE. If a patient dies during participation in the study or during a recognized follow-up 
period, the sponsor will be provided with a copy of any post-mortem findings, including 
histopathology. 
New or updated information will be recorded on a new SAE form and the CRF. The updated SAE 
form should be sent to the sponsor.  
16.7 Exposure In Utero Management and Reporting 
In instances of pregnancies or suspected pregnancies (including a positive pregnancy test 
regardless of age) while the patient is on investigational product: 
 Female patient - dosing of the investigational product must be discontinued immediately. 
The pregnant patient should be advised to call her healthcare provider. 
 Partner of male patient - dosing of the investigational product to the male patient may 
continue at the discretion of the investigator. The pregnant partner of the male patient 
should be advised to call her healthcare provider. 
The investigator will notify the sponsor and designated study safety officer of this event and 
document the pregnancy on the Exposure in Utero Form as described in the study Safety 
Reporting Plan.  
The investigator shall obtain Informed Consent from the pregnant patient (or the pregnant partner 
of the male patient) in order to allow him/her (or delegate) to conduct follow-up throughout the 
gestational period and on the infant following delivery. The investigator shall follow-up newborn 
infants that have been exposed to investigational product in utero for a minimum of 6 months. 
Upon discovery of any congenital anomalies (or neonatal deaths) the investigator shall submit a 
follow-up report to the sponsor (and study safety officer) using an SAE Form (as per study Safety 
Reporting Plan) including information regarding the status of the newborn. A miscarriage or 
abortion shall also be reported by the investigator to the study Safety Officer (and the sponsor) 
using an SAE Form. 
17 PATIENTS LOST TO FOLLOW-UP AFTER IMPLANTATION 
When a subject is “lost to follow-up” (i.e., fails to return for study visits), a reasonable effort will 
be made to contact him/her to determine a reason for the failure to return and encourage the 
subject to return for removal of the implant. The detailed plan that the research center will follow 
in attempts to contact a subject that fails to return for a visit is listed below. 
In the event a subject misses a scheduled outpatient visit during the study, the following 
procedures will be conducted to locate the patient:   
 The study coordinator will attempt to contact the subject (e.g., phone, email, or text) for 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 77 of 101 
 
four consecutive weeks in an effort to locate the subject and coordinate his/her return to 
the research site. 
 If unsuccessful in contacting the subject the coordinator will contact the subject’s 
caregiver/emergency contact. 
 Once contact is established, the Investigator will assess the subject’s ability to continue in 
the study. 
 If the patient does not contact the site, the Sponsor will request for a third party to locate 
the patient to have the implant removed. 
All attempts to contact the subject must be documented in the source data.  The subject will be 
considered lost to follow up if the subject is not successfully located using the plan outlined above 
and should be identified as “lost to follow-up” in the CRF. However, the research site will request 
that all listed contacts continue to monitor for the subject and request that they call the emergency 
numbers if contact is made with the subject. The research site will also continue to monitor their 
psychiatric network in efforts to locate the subject. 
18 STATISTICS AND DATA ANALYSIS  
This section describes the general framework to be used for the analysis and presentation of data 
in this study. The information described in this section may be revised during the study to 
accommodate protocol amendments and to make changes to adapt to unexpected issues in study 
execution and data that could affect planned analyses. All available data will be included in data 
listings and tabulations. No imputation of values for missing data will be performed. A formal 
Statistical Analysis Plan will be issued prior to database lock. 
18.1 Sample Size Considerations 
The maximum sample size is 30. The primary objective of this study is to determine safety and 
tolerability of DLP-114 and as such the sample size for this study was based upon qualitative 
considerations. No formal sample size calculations were performed.  
18.2 Demographic Data 
For all patients who received at least 1 dose of study treatment, descriptive statistics (mean, 
standard deviation, median, minimum, maximum) will be performed for age, gender, body mass 
index, weight, and height.  
18.3 Safety/Tolerability Data 
All patients who receive at least 1 dose of study treatment will be included in the safety and 
tolerability analysis. Baseline for all vital signs, 12-lead ECG measurements, and clinical 
laboratory assessments will be defined as the last evaluation done before the start of study 
treatment administration on Day -4. 
Safety evaluations will be based on the incidence, intensity and type of AE and clinically 
significant changes in the patient’s physical examination findings, vital signs, 12-lead ECGs, and 
clinical laboratory results. Safety variables will be tabulated and presented for all patients who 
receive study treatment, i.e., the safety population. 
Abnormalities in clinical laboratory, vital signs, and ECG will be based on pre-defined normal 
ranges and will be tabulated by study treatment showing patient counts and percentages. 
The original terms used in the CRF by investigators to identify AEs will be coded using the 
current version of the Medical Dictionary of Regulatory Activities (MedDRA). The percentage of 
patients with treatment-emergent AEs will be summarized for each treatment. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 78 of 101 
 
Special attention will be given to those patients who have discontinued treatment due to an AE or 
who experienced a severe or a SAE. 
Laboratory data will be summarized by the type of laboratory test. Normal reference ranges and 
markedly abnormal results will be used in the summary of laboratory data. Raw data and change 
from baseline in clinical laboratory parameters will be summarized using descriptive statistics. A 
listing of patients with any laboratory results outside the reference ranges that are deemed 
clinically significant will be provided. 
18.4 Pharmacokinetic Data 
Plasma concentrations of plasma concentrations of risperidone, 9-OH risperidone and active 
moiety (risperidone + 9 OH risperidone) determined at specified time points will be used to 
calculate PK parameters. Data will be listed for all patients with available plasma concentrations 
of risperidone, 9-OH risperidone and active moiety (risperidone + 9 OH risperidone). All 
concentrations below the limit of quantification (LOQ) or missing data will be labeled as such in 
the concentration data listings. Concentrations designated as LOQ will be treated as 0 in the 
summary statistics and for the calculation of PK parameters.  
Reasons for exclusion of a patient or a sample from the analysis include, but are not limited, to 
the following: 
 
Vomiting within 6 hours after investigational product administration (oral risperidone 
only); 
 
Too few data (greater than 10% missing values for a patient); 
 
Noncompliance with study procedures affecting pharmacokinetics (e.g., concomitant 
medication). 
All patients and samples excluded from the analysis will be clearly documented in the PK study 
report. Pharmacokinetic parameters for risperidone, 9-OH risperidone and active moiety 
(risperidone + 9 OH risperidone) will be calculated using non-compartmental analysis. Only 
plasma concentrations greater than the LOQ for the assay will be used in the PK analysis. Actual 
sampling times will be used in all PK analyses. Per protocol times will be used to calculate mean 
plasma concentrations for graphical displays.  
Listing of individual patient plasma concentrations, actual blood sampling times, and PK 
parameters and graphs of concentration vs. time will be prepared by study treatment. Plasma 
concentrations and PK parameters will be summarized by and compared between study 
treatments using descriptive statistics. 
Statistical analysis will be performed on the pharmacokinetic parameters using validated 
statistical software. 
19 DATA HANDLING AND RECORDKEEPING 
19.1 Patient Identification and Enrolment Log and Patient Screening Log 
The investigator agrees to complete a patient identification and enrollment log to permit easy 
identification of each patient during and after the study. This document will be reviewed by the 
sponsor site contact for completeness. 
The patient enrollment log will be treated as confidential and will be filed by the investigator in 
the Investigator Site File (ISF). All reports and communications relating to the study will identify 
patients by initials and assigned number only. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 79 of 101 
 
The investigator must also complete a patient screening log, which reports on all patients who 
were seen to determine eligibility for inclusion in the study. 
19.2 Source Documentation 
Source documentation must be available to substantiate patient identification, eligibility, and 
participation; proper informed consent procedures; dates of visits; adherence to protocol 
procedures; records of safety parameters; adequate reporting and follow-up of adverse events; 
administration of concomitant medication; drug receipt/dispensing/return records; investigational 
product administration information; and date of patient completion, discontinuation from 
treatment, or withdrawal from the study, and the reason if appropriate. Specific items required as 
source documents will be reviewed with the investigator before the study. 
At a minimum the following data must be maintained in source documentation: patient 
identification, patient eligibility, exposure to investigational product, adverse events, and 
concomitant medication. It is recommended that the author of an entry in the source documents be 
identifiable. Worksheets may be used for the capture of some data to facilitate completion of the 
CRF. Any such worksheets will become part of the patients’ source documentation. 
Following the ICH-GCP guidelines, direct access to source documentation (medical records) must 
be allowed for the purpose of verifying that the data recorded in the CRF are consistent with the 
original source data. 
19.3 Case Report Form 
A CRF must be completed for each patient who has received at least 1 supervised dose of 3 
mg/day risperidone.  
For reasons of confidentiality, the name of the patient should not appear in the CRF. All CRF 
entries, corrections, and alterations must be made by the investigator or other authorized study-
site personnel. 
CRFs will be completed according to the sponsor’s (or designee) instructions and reviewed by the 
sponsor (or designee) to determine their accuracy and acceptability. If necessary, CRF queries 
will be raised by the sponsor (or designee) relating to CRF data entries. The investigator or 
authorized study site staff must address all CRF queries raised. 
20 ETHICS AND REGULATORY COMPLIANCE 
20.1 Investigator Responsibilities 
The investigator agrees to conduct the clinical study in accordance with the protocol, current 
International Council on Harmonization (ICH) guidelines for Good Clinical Practice (GCP), and 
applicable regulatory and legal requirements. GCP is an international ethical and scientific quality 
standard for designing, conducting, recording, and reporting studies that involve the participation 
of human patients. Compliance with this standard provides public assurance that the rights, safety, 
and well-being of study patients are protected, consistent with the principles that originated in the 
Declaration of Helsinki, and that the clinical study data are credible. 
20.2 Independent Ethics Committee or Institutional Review Board (IEC/IRB) 
This study protocol and any amendment(s) must be submitted to the appropriate regulatory 
authorities in each respective country, as required. The sponsor (or designee) is responsible for 
regulatory submissions. This clinical study may not be initiated until all local regulatory 
requirements are met. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 80 of 101 
 
Before the start of the study, a written favorable opinion or approval must be received from the 
IEC/IRB. To achieve this, the investigator or the sponsor will submit to the IEC/IRB, as required 
by local regulations, current and complete copies of relevant documents. 
The written favorable opinion or approval must be dated and must clearly identify the documents 
reviewed, which should include the final protocol and any amendments, the informed consent 
form, applicable recruiting materials, and any patient compensation program. 
During the study, the investigator or sponsor, as required, will submit the following for IEC/IRB 
review or opinion/approval: 
1. Revisions or updates of documents previously submitted to the IEC/IRB 
2. Relevant new information or documents, as required: 
a. Summaries of the status of the study (at least annually or at intervals stipulated in 
guidelines of the IEC/IRB); 
b. Reports of adverse events that are serious, unlisted, and associated with the 
investigational drug; 
c. Deviations from or changes to the study protocol to eliminate immediate hazards 
to the patients. 
When and where required by local regulations, before implementation of any change, study 
protocol amendments and revised documents must receive IEC/IRB favorable opinion or 
approval. 
The IEC/IRB will be given official notification of the study completion. 
20.3 Required Pre-study Documentation 
The study protocol and any amendment(s) signed and dated by the investigator, the completed 
investigator financial disclosure form from the investigator, and signed and dated statement of 
investigator (e.g., Form FDA 1572), if applicable, and any other documents specified by ICH-
GCP guidelines must be provided to the sponsor before the study is started at an investigational 
site. 
20.4 Clinical Laboratory Certification and Reference Ranges 
Before the initiation of this study, the investigator (or nominee) will obtain a copy of the 
certification form, with certification number and expiration date for all clinical laboratories used 
in the study. Reference ranges for each clinical laboratory test used in this study will be obtained 
from the appropriate laboratory, which will perform the test for the study. 
20.5 Informed Consent 
Each patient must give written consent according to local requirements after receiving a full 
explanation of the nature of the study. The consent form must be signed before performance of 
any study-related activity. The consent form that is used must be approved by both the sponsor 
and by the reviewing IEC/IRB. The informed consent process and form should be in accordance 
with principles that originated in the Declaration of Helsinki, current ICH-GCP guidelines, 
applicable regulatory requirements, and sponsor policy. 
Before a patient’s entry into the study, the investigator or an authorized member of the clinical 
staff must explain to the potential patient the aims, methods, and potential hazards of the study, 
and any discomfort it may entail. Patients will be informed that their participation is voluntary 
and that they may withdraw consent to participate at any time. They will be informed that 
choosing not to participate will not affect the care a patient will receive. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 81 of 101 
 
Finally, patients will be informed that the investigator will maintain a patient enrolment log for 
the purposes of long-term follow-up if needed and that their records may be accessed by health 
authorities and authorized sponsor staff without violating the confidentiality of the patient, to the 
extent permitted by the applicable law(s) or regulations. By signing the informed consent form the 
patient is authorizing such access, and agrees to be re-contacted after study completion, by health 
authorities and authorized sponsor staff, for the purpose of obtaining consent for additional safety 
evaluations if needed. 
Patients will be given sufficient time to read the informed consent form and the opportunity to ask 
questions. After this explanation and before entry into the study, consent should be appropriately 
recorded by means of the patient's personally dated signature. After the consent is obtained, a 
copy of the informed consent form must be given to the patient. 
20.6 Privacy of Personal Data 
In order to maintain patient privacy, all CRF, investigational product accountability records, study 
reports and communications will identify the patient by initials and the assigned patient number. 
The investigator will grant monitor(s) and auditor(s) from Delpor (or designee) and regulatory 
authorities access to the patient’s original medical records for verification of data gathered on the 
CRF and to audit the data collection process. The patient’s confidentiality will be maintained and 
will not be made publicly available to the extent permitted by the applicable laws and regulations. 
20.7 Study Completion/Site Closure 
The study is considered completed at the last visit of the last patient undergoing the study. The 
final data from the investigational site will be sent to the sponsor (or designee) in the time frame 
specified in the Clinical Trial Agreement. Investigational sites will be closed upon study 
completion. An investigational site is considered closed when all required documents and study 
supplies have been collected and a site closure visit has been performed. 
21 QUALITY CONTROL AND ASSURANCE 
21.1 Study Monitoring 
The sponsor will assign monitors who will perform on-site monitoring visits as frequently as 
necessary and in compliance with the ICH-GCP Section 5.18.4. 
Monitoring visits will include checking the CRF for completeness and clarity, cross-checking 
with source documents, and clarification of administrative matters. Findings from the review of 
CRF and source documents will be discussed with the clinical staff. 
The sponsor expects that, during monitoring visits, the relevant clinical staff will be available, the 
source documentation will be accessible, and a suitable environment will be provided for review 
of study-related documents. The monitor will meet with the investigator on a regular basis during 
the study to provide feedback on the study conduct. 
21.2 Audits, Inspections Study Quality Management 
To ensure compliance with ICH GCP and all applicable regulatory requirements, Delpor (or a 
designated third party), may conduct a quality assurance audit of the study site. Regulatory 
agencies may also conduct a regulatory inspection of this study. Such audits/inspections can occur 
at any time during or after completion of the study. If an audit or inspection occurs, the 
investigator and institution agree to notify the sponsor as soon as possible following awareness of 
an impending regulatory inspection. The investigator and Institution agree to allow the 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 82 of 101 
 
auditor/inspector direct access to all relevant documents and allocate his/her time and the time of 
his/her staff to the auditor/inspector to discuss findings and any relevant issues. 
The sponsor (or its designee) will perform the quality assurance and quality control activities of 
this study; however, responsibility for the accuracy, completeness, and reliability of the study data 
presented to the sponsor lies with the investigator (and delegate(s)) generating the data. 
Prior to the study initiation, the sponsor (or its designee) will explain the protocol, Investigator’s 
Brochure, and CRF to the investigator and clinical facility staff involved in this study. In addition, 
the assigned study monitor will be available to explain applicable regulations and to answer any 
questions regarding the conduct of the study. 
21.3 Data Quality Control 
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study centers, review of protocol procedures with the investigator 
and associated personnel before the study, and periodic monitoring visits by the sponsor (or 
designee). Written instructions will be provided for collection, preparation, and shipment of 
blood, plasma, and urine samples. CRF completion training will be conducted with study 
personnel before the start of the study. The sponsor’s monitor will review electronic data for 
accuracy and completeness during onsite monitoring visits and after his/her return to the 
sponsor’s office; any discrepancies will be resolved with the investigator or designee, as 
appropriate. The data will be entered into the clinical study database and verified for accuracy. 
21.4 Record Retention 
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all source 
documents that support the data collected from each patient, as well as all study documents as 
specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical Trial, and all 
study documents as specified by the applicable regulatory requirement(s). The 
investigator/institution will take measures to prevent accidental or premature destruction of these 
documents. 
Essential documents must be retained as per the applicable regulatory requirements for the 
country where the site is located or by an agreement with the sponsor. It is the responsibility of 
the sponsor to inform the investigator/institution as to when these documents no longer need to be 
retained. 
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The sponsor must be notified in writing of the name and address of the 
new custodian. 
Under no circumstance shall the investigator relocate or dispose of any study documents before 
having obtained written approval from the sponsor. 
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator must permit access to all study 
documentation. 
22 STUDY PROTOCOL GUIDELINES 
22.1 Protocol Amendments, Deviations and Violations 
Neither the investigator nor the sponsor will modify this protocol without a formal amendment. 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 83 of 101 
 
All protocol amendments must be issued by the sponsor, and signed and dated by the investigator. 
Protocol amendments must not be implemented without prior IEC/IRB approval, or when the 
relevant competent authority has raised any grounds for non-acceptance, except when necessary 
to eliminate immediate hazards to the patients, in which case the amendment must be promptly 
submitted to the IEC/IRB and relevant competent authority. When the amendment(s) involves 
only logistic or administrative aspects of the study, the IRB (and IEC where required) needs only 
to be notified. 
A protocol deviation is an accidental or unintentional change to, or non-compliance with this 
study protocol that does not increase risk or decrease benefit or; does not have a significant effect 
on the patient’s rights, safety or welfare; and/or on the integrity of the data. No deviations to this 
protocol are permitted, except in instances when an emergency occurs that requires a departure 
from the protocol to protect the safety of an individual.  
A protocol violation is an accidental or unintentional change to, or non-compliance with the 
IEC/IRB approved protocol (without prior sponsor and IEC/IRB approval), which increases the 
risk or decreases the benefit, affects the patient’s rights, safety, or welfare, or the integrity of the 
data. Reporting of protocol violations to IEC/IRB and in accordance with applicable Regulatory 
Authority mandates is an Investigator responsibility. 
In situations requiring a departure from the protocol, the investigator (or other physician) in 
attendance will contact the appropriate sponsor representative by fax or telephone or e-mail (see 
Contact Information pages provided separately). If possible, this contact will be made before 
implementing any departure from the protocol. In all cases, contact with the sponsor must be 
made as soon as possible to discuss the situation and agree on an appropriate course of action. 
The data recorded in the CRF and source document will reflect any departure from the protocol, 
and the source documents will describe this departure and the circumstances requiring it. 
23 USE OF INFORMATION AND PUBLICATION POLICY  
All information, including but not limited to information regarding DLP-114 or the sponsor’s 
operations (e.g., patent application, formulas, manufacturing processes, basic scientific data, prior 
clinical data, formulation information) supplied by the sponsor to the investigator and not 
previously published, and any data generated as a result of this study, are considered confidential 
and remains the sole property of the sponsor. The investigator agrees to maintain this information 
in confidence and to use this information only to conduct this study, and will not use it for other 
purposes without the sponsor’s prior written consent. 
The investigator understands that the information developed in the clinical study will be used by 
the sponsor in connection with the continued development of DLP-114, and thus may be 
disclosed as required to other clinical investigators or regulatory agencies. To permit the 
information derived from the clinical studies to be used, the investigator is obligated to provide 
the sponsor with all data obtained in the study. The results of the study will be reported in a 
Clinical Study Report generated by the sponsor (or designee) under the supervision of the sponsor 
and will contain all data from all investigational sites. Any work created in connection with 
performance of the study and contained in the data that can benefit from copyright protection 
(except any publication by the investigator as provided for below) shall be the property of the 
sponsor as author and owner of copyright in such work. The sponsor shall have the right to 
publish such data and information without approval from the investigator. If an investigator 
wishes to publish information from the study, a copy of the manuscript must be provided to the 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 84 of 101 
 
sponsor for review at least 60 days before submission for publication or presentation. Expedited 
reviews will be arranged for abstracts, poster presentations, or other materials. If requested by the 
sponsor in writing, the investigator will withhold such publication for up to an additional 60 days 
to allow for filing of a patent application. In the event that issues arise regarding scientific 
integrity or regulatory compliance, the sponsor will review these issues with the investigator. The 
sponsor will not mandate modifications to scientific content and does not have the right to 
suppress information. The investigator will recognize the integrity of a multi-center study by not 
publishing data derived from the individual site until the combined results from the completed 
study have been published in full, within 12 months after conclusion, abandonment, or 
termination of the study at all sites, or the sponsor confirms there will be no multi-center study 
publication. Authorship of publications resulting from this study will be based on generally 
accepted criteria for major medical journals. 
24 LIABILITY AND INSURANCE 
The investigator is required to have adequate current insurance to cover claims for negligence 
and/or malpractice. The sponsor will provide insurance coverage for the clinical study as required 
by national regulations. Delpor will be subscribed to an insurance policy covering, in its terms 
and provisions, its legal liability for injuries caused to participating persons and arising out of this 
research performed strictly in accordance with the study protocol as well as with applicable law 
and professional standards prior to the dosing of the first patient. 
25 REFERENCES 
1- FDA, Viadur (leuprolide acetate implant). Reference ID: 2888026 
[http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021088s025lbl.pdf], 2010. 
2- FDA, Vantas Prescribing Information. Reference ID: 2887911 
[http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021732s013lbl.pdf], 2010. 
3- Walsh, C.T., S.W. Haynes, and B.D. Ames, Aminobenzoates as building blocks for 
natural product assembly lines. Nat Prod Rep, 2012. 29(1): p. 37-59. 
4- Hanson, A.D. and J.F. Gregory, 3rd, Folate biosynthesis, turnover, and transport in plants. 
Annu Rev Plant Biol, 2011. 62: p. 105-25. 
5- Rea, W.J., Chemical Sensitivity. 1992, Lewis Publishers: Boca Raton. p. 266. 
6- USDA, What We Eat in America NHANES. 
7- Oquendo MA, Halberstam B, Mann JJ. Colombia Suicide Severity Rating Scale (C-SSRS) 
– Risk Factors for Suicidal Behavior: The Utility and Limitations of Research Instruments, 
in Standardized Evaluation in Clinical Practice. First MB, editor. American Psychiatric 
Publishing; Washington, DC: 2003: 103-131. 
 
 
 
 
 

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 85 of 101 
 
26 APPENDICES 
26.1 APPENDIX 1. Overall Schedule of Assessments 
 
Group 1 
  
Treatment Period 
Screening
Conversion 
Phase1
Follow 
Up
EOS
ET24
ET 
Oral
Study Day
Varies (28 day 
window)
Varies to ‐5
‐7
‐6
‐5
‐4
‐3
‐2
‐1
1
2
3
4
5
6
7
14
21
28
42
56
70
84
98
112
126
140
154
168
183
184
185
186
190
Confinement
X
X
X
X
X
X
X
X
X
Outpatient Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Cross titrate from other antipsychotic to 2-3 mg/day risperidone1
X
Informed Consent
X
Review of Eligibility Criteria
X
Demographics
X
Medical History
X
Height
X
X
Body Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Calculation of BMI
X
X
Review of Prior Medications
X
X
Physical Examination (Complete)
X
X
X
Viral Serology
X
Alcohol Breath Test4
X
X
Urine Drug Screen4
X
X
X
X
Serum hCG Pregnancy Test2
X
Urine hCG Pregnancy Test2,4
X
X
X
X
X
X
X
X
X
X
X
Safety Laboratory Tests (blood)4
X
X
X
X
X
X
X11
X11
X11
Safety Laboratory Tests (urine)4
X
X
X
X
X
X
X11
X11
X
12-lead ECG3,4
X
X
X7
X9
X
X
X
X
X11
X11
X
Vital Signs25
X
X
X5
X
X
X5
X6,8
X9
X10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X12
X13
X14
X
X
X12
X
CYP2D6 Genotype
X
CGI-S
X
X
CGI-I4
X
X
X
X
X
X
X
X
X
X
PANSS4
X
X
X
X
X
C-SSRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BARS4
X
X
X
X
SAS4
X
X
X
X
AIMS3
X
X
X
X
Self Administration of Investigational Product Under Supervision (Oral)
X
X
X
X
X19
X9
Self Administration of Investigational Product Not Under Supervision (Oral)
X
X
X
Adverse Event Monitoring
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Update/Review of Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sampling for PK16
X17,18
X19,20
X21
X22
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X23
X13
X14
X
X15
Implant Device Administration
X
Issuing of study card and/or safety alert bracelet
X
Implant Site Inspection
X
X9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X13
X14
X
X
X
Ultrasound4
X
X
Implant removal
X
X
ASSESSMENT
Implant Treatment Period
Oral Treatment Period 
(Unsupervised)
Oral Treatment Period 
(Supervised)
Implant + Oral 
Period
Recovery 
Period

 
Study Protocol 
Protocol No.: DLP-114-03 
 
 
Delpor Inc 
Page 86 of 101 
 
 
Group 2 
 
 
 
 
Treatment Period 
Screening
Conversion 
Phase1
Follow 
Up
EOS
ET24
ET Oral
Study Day
Varies (28 day 
window)
Varies to ‐5
‐7
‐6
‐5
‐4
‐3
‐2
‐1
1
2
3
4
5
6
7
14
21
28
42
56
70
84
98
112
126
140
154
168
182
196
210
224
238
252
266
280
294
308
322
336
350
364
365
366
367
371
Confinement
X
X
X
X
X
X
X
X
X
Outpatient Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Cross titrate from other antipsychotic to 2-3 mg/day risperidone1
X
Informed Consent
X
Review of Eligibility Criteria
X
X
Demographics
X
Medical History
X
Height
X
X
Body Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Calculation of BMI
X
X
Review of Prior Medications
X
X
Physical Examination (Complete)
X
X
X
Viral Serology
X
Alcohol Breath Test4
X
X
Urine Drug Screen4
X
X
X
X
X
Serum hCG Pregnancy Test 2
X
Urine hCG Pregnancy Test2,4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety Laboratory Tests (blood)4
X
X
X
X
X
X
X
X
X
X
X11
X11
X11
Safety Laboratory Tests (urine)3
X
X
X
X
X
X
X
X
X
X
X10
X11
X
12-lead ECG3,4
X
X
X7
X9
X
X
X
X
X
X
X
X
X11
X10
X
Vital Signs25
X
X
X5
X
X
X5
X57
X8
X10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X12
X13
X14
X
X
X12
X
CYP2D6 Genotype
X
CGI-S
X
X
CGI-I4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PANSS4
X
X
X
X
X
X
X
C-SSRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BARS4
X
X
X
X
X
X
X
X
SAS4
X
X
X
X
X
X
X
X
AIMS4
X
X
X
X
X
X
X
X
Self Administration of Investigational Product Under Supervision (Oral)
X
X
X
X
X19
X9
Self Administration of Investigational Product Not Under Supervision (Oral)
X
X
X
Adverse Event Monitoring
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Update/Review of Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Sampling for PK16
X17,18
X19,20
X21
X22
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X23
X13
X14
X
X15
Implant Device Administration
X
Issuing of study card and/or safety alert bracelet
X
Implant Site Inspection
X
X9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X13
X14
X
X
X
Ultrasound4
X
X
Implant removal
X
X
ASSESSMENT
Implant Treatment Period
Oral Treatment Period 
(Unsupervised)
Oral Treatment Period 
(Supervised)
Implant + Oral 
Period
Recovery 
Period

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 87 of 101 
 
Footnotes: Overall Schedule of Assessments (6-month arm and 12-month arm) 
 
1 Patients who are stable on an antipsychotic other than oral risperidone (2-3 mg/day) will 
have weekly visits during the conversion phase, during which they will cross-titrate, at the 
PI’s discretion, from the other antipsychotic(s) to oral risperidone therapy over a 
minimum of 2 weeks. The objective of the oral conversion phase is for all subjects to 
achieve an oral risperidone dose of 3 mg by Day -14 
2 Females only 
3 All ECGs should be obtained prior to vital signs and blood sampling when applicable. 
4 May be performed more frequently based on symptoms at the PI's discretion 
5 Pre-dose 
6 Pre-implantation 
7 4 hours post-implantation 
8 Every hour for the first 8 hours post-implantation 
9 Approximately 24 hours post-implantation 
10 Approximately 48 hours post-implantation 
11 4 hours following removal of the DLP-114 implant 
12 Every hour for the first 4 hours following removal of the DLP-114 implant 
13 24 hours following removal of the DLP-114 implant 
14 48 hours following removal of the DLP-114 implant 
15 Prior to removal 
16 See Appendix 2. Pharmacokinetic sample collection schedule 
17 Within 10 min prior to dose administration 
18 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose 
19 1 hour (± 30 min) prior to DLP-114 implantation 
20 1, 2, 3, 4, 6, 8 and 12 hours post-implantation 
21 24, 28, 32 and 36 hours following implantation of DLP-114 
22 48 and 52 hours following implantation of DLP-114 
23 1, 2, 3, 4, 6, 8- and 12-hours following removal of the DLP-114 implant 
24 Patients will be requested to return to the clinic for a follow up visit 6 (±3) days 
following the removal of the implant, for implant site inspection and AE assessment. 
25 Vital signs will include systolic and diastolic blood pressure, pulse, body temperature, 
and respiratory rate. In addition, orthostatic blood pressure and pulse will be collected 
after 1, 3, and 5 minutes standing at Screening, on Day 1 prior to the implant and 4 hours 
post-implantation, and on Day 3 approximately 48 hours post-implantation 
 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 88 of 101 
 
26.2 APPENDIX 2. Pharmacokinetic Sample Collection Schedule 
Group 1 
Treatment 
Day 
Study Event 
Hours 
Time Window 
Sample 
No. 
Oral 
Risperidone (3 
mg/day) 
‐1 
  
‐0.17 
Within 10 min prior to dosing 
1 
Dose (Oral Risperidone 3 mg) 
0 
  
  
  
0.5 
±2 min 
2 
  
1 
±5 min 
3 
  
2 
±15 min 
4 
  
3 
±15 min 
5 
  
4 
±15 min 
6 
  
6 
±15 min 
7 
  
8 
±15 min 
8 
  
12 
±15 min 
9 
0 
 
24 
±15 min 
10 
Co‐
administration 
of Oral 
Risperidone (3 
mg/day) and 
2X DLP‐114 
Implants 
1 
Dose (Oral Risperidone 3 mg)  
‐1 
±30 min 
11 
2 x DLP‐114 Device 
Implantation 
0 
  
  
  
1 
±5 min 
12 
  
2 
±15 min 
13 
  
3 
±15 min 
14 
  
4 
±15 min 
15 
  
6 
±15 min 
16 
  
8 
±15 min 
17 
  
12 
±15 min 
18 
2 
Dose (Oral Risperidone 3 
mg)   
24 
±15 min 
19 
  
28 
±15 min 
20 
  
32 
±15 min 
21 
  
36 
±15 min 
22 
2X DLP‐114 
Implants 
3 
  
48 
±15 min 
23 
  
52 
±15 min 
24 
4 
  
AM* 
±1 day 
25 
5 
 
AM* 
±1 day 
26 
6 
 
AM* 
±1 day 
27 
7 
  
AM* 
±1 day 
28 
14 
  
AM* 
±1 day 
29 
21 
  
AM* 
±1 day 
30 
28 
  
AM* 
±1 day 
31 
42 
  
AM* 
±1 day 
32 
56 
  
AM* 
±1 day 
33 
70 
  
AM* 
±1 day 
34 
84 
  
AM* 
±1 day 
35 
98 
  
AM* 
±1 day 
36 
112 
  
AM* 
±1 day 
37 
126 
  
AM* 
±1 day 
38 
140 
  
AM* 
±1 day 
39 
154 
  
AM* 
±1 day 
40 
168 
  
AM* 
±1 day 
41 
183 ± 
7 
days 
 
 ‐1 
 ±15 min 
42 
Recovery 
DLP‐114 Removal 
 0 
  
  
  
1 
±5 min 
43 
  
2 
±15 min 
44 
  
3 
±15 min 
45 
  
4 
±15 min 
46 
  
6 
±15 min 
47 
  
8 
±15 min 
48 
  
12 
±15 min 
49 
184 
  
24 
±60 min 
50 
185 
  
48 
±60 min 
51 
Follow‐Up 
186 
 
72 
±60 min 
52 
 
Early 
Termination 
ET 
 
‐1 
±45 min 
 
DLP‐114 Removal 
0 
 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 89 of 101 
 
Treatment 
Day 
Study Event 
Hours 
Time Window 
Sample 
No. 
 
* 8 AM‐12 Noon on the morning of the designated Study Day. 
 
Group 2 
Treatment 
Day 
Study Event 
Hours 
Time Window 
Sample 
No. 
Oral 
Risperidone (3 
mg/day) 
‐1 
  
‐0.17 
Within 10 min prior to dosing 
1 
Dose (Oral Risperidone 3 mg) 
0 
  
  
  
0.5 
±2 min 
2 
  
1 
±5 min 
3 
  
2 
±15 min 
4 
  
3 
±15 min 
5 
  
4 
±15 min 
6 
  
6 
±15 min 
7 
  
8 
±15 min 
8 
  
12 
±15 min 
9 
0 
 
24 
±15 min 
10 
Co‐
administration 
of Oral 
Risperidone (3 
mg/day) and 
2X DLP‐114 
Implants 
1 
Dose (Oral Risperidone 3 mg)  
‐1 
±30 min 
11 
2 x DLP‐114 Device 
Implantation 
0 
  
  
  
1 
±5 min 
12 
  
2 
±15 min 
13 
  
3 
±15 min 
14 
  
4 
±15 min 
15 
  
6 
±15 min 
16 
  
8 
±15 min 
17 
  
12 
±15 min 
18 
2 
Dose (Oral Risperidone 3 
mg)   
24 
±15 min 
19 
  
28 
±15 min 
20 
  
32 
±15 min 
21 
  
36 
±15 min 
22 
2X DLP‐114 
Implants 
3 
  
48 
±15 min 
23 
  
52 
±15 min 
24 
4 
  
AM* 
±1 day 
25 
5 
 
AM* 
±1 day 
26 
6 
 
AM* 
±1 day 
27 
7 
  
AM* 
±1 day 
28 
14 
  
AM* 
±1 day 
29 
21 
  
AM* 
±1 day 
30 
28 
  
AM* 
±1 day 
31 
42 
  
AM* 
±1 day 
32 
56 
  
AM* 
±1 day 
33 
70 
  
AM* 
±1 day 
34 
84 
  
AM* 
±1 day 
35 
98 
  
AM* 
±1 day 
36 
112 
  
AM* 
±1 day 
37 
126 
  
AM* 
±1 day 
38 
140 
  
AM* 
±1 day 
39 
154 
  
AM* 
±1 day 
40 
168 
  
AM* 
±1 day 
41 
182 
  
AM* 
±1 day 
42 
196 
 
AM* 
±1 day 
43 
210 
  
AM* 
±1 day 
44 
224 
 
AM* 
±1 day 
45 
238 
 
AM* 
±1 day 
46 
252 
 
AM* 
±1 day 
47 
266 
 
AM* 
±1 day 
48 
280 
 
AM* 
±1 day 
49 
294 
 
AM* 
±1 day 
50 
308 
 
AM* 
±1 day 
51 
322 
 
AM* 
±1 day 
52 
336 
 
AM* 
±1 day 
 53 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 90 of 101 
 
Treatment 
Day 
Study Event 
Hours 
Time Window 
Sample 
No. 
350 
 
AM* 
±1 day 
54 
364 ± 
7 
days 
 
 ‐1 
±45 min 
55 
Recovery 
DLP‐114 Removal 
 0 
  
  
  
1 
±5 min 
56 
  
2 
±15 min 
57 
  
3 
±15 min 
58 
  
4 
±15 min 
59 
  
6 
±15 min 
60 
  
8 
±15 min 
61 
  
12 
±15 min 
62 
365 
  
24 
±60 min 
63 
366 
  
48 
±60 min 
64 
Follow‐Up 
367 
 
72 
±60 min 
65 
 
Early 
Termination 
ET 
 
‐1 
±45 min 
 
DLP‐114 Removal 
0 
 
 
 
* 8 AM‐12 Noon on the morning of the designated Study Day. 
 
 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 91 of 101 
 
 
26.3 APPENDIX 3. Skin Irritation Scoring System 
(Kim, Choi et al, Drug Design and Therapy 2015, 8, 1419)[1] 
 
Dermal Response: 
0 = no evidence of irritation 
1 = minimal erythema, barely perceptible 
2 = definite erythema, readily visible; minimal edema or minimal popular response 
3 = erythema and papules 
4 = definite edema 
5 = erythema, edema, and papules 
6 = vesicular eruption 
7 = strong reaction spreading beyond test site 
 
Other Effects: 
A = slight glazed appearance 
B = marked glazing 
C = glazing with peeling and cracking 
F = glazing with fissures 
G = film of dried serous exudate covering all or part of the patch* site 
H = small petechial erosions and/or scabs 
 
*For this study this refers to the implantation site and surrounding area. 
 
 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 92 of 101 
 
26.4 APPENDIX 4. Risperdal® (risperidone) Product Information 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 93 of 101 
 
 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 94 of 101 
 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 95 of 101 
 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 96 of 101 
 
 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 97 of 101 
 
 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 98 of 101 
 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 99 of 101 
 
26.5 APPENDIX 5. Instructions for Use (IFU) 
 
 
 
 

INSTRUCTIONS FOR USE
DLP-114
Risperidone Implant
For Investigational Use Only
Instructions for Use
Risperidone Implant, DLP-114

Contents
About DLP-114……………………………………………………………………………......2
Safety Information………………………………………………….............................3
Symbols Glossary.......................................................................................5
Supplies…………………………………………………………………………………........... 6
Procedure Overview..................................................................................7
Implantation Procedure
	
1. Hydrate Implant…………………………………………………................ 9
	
	
Prepare saline vial
	
	
Fill hydration syringe
	
	
Inject saline into implant vial
	
	
Repeat for all implants
	
2. Prepare Implantation Site……………………………………...............11
	
	
Position patient
	
	
Mark implantation site
	
	
Clean the site
	
	
Wash hands
	
	
Put on latex-free gloves
	
	
Lay out surgical instruments
	
	
Clean implantation site
	
	
Apply anesthetic
	
	
Make incision at an angle
	
	
Use hemostat tip to deepen pocket
	
3. Load Implant Device.................................................................16
	
	
Pour contents from implant vial
	
	
Check implanter tool position
	
	
Load implant in implanter tool
	
4. Insert Implant............................................................................17
	
	
Insert cannula tip
	
	
Slide cannula through pocket
	
	
Deploy implant
	
	
Insert additional implants if needed
	
5. Complete Procedure.................................................................19
	
	
Dispose of implanter tool and vial(s)
	
	
Close incision
	
	
After-procedure care
Explant Procedure
	
1. Prepare Explant site……………………………………........................ 23
	
	
Wash hands
	
	
Put on latex-free gloves
	
	
Locate implant
	
	
Clean removal site
	
	
Apply anesthetic
	
2. Remove Implant Device……………………………………………......... 25
	
	
Make incision with forceps support
	
	
Remove implant with grasping forceps
	
	
Repeat for additional implants if needed
	
3. Complete Procedure.................................................................26
	
	
Dispose of implant(s)
	
	
Close incision
1

About DLP-114
DLP-114 Implant Device
DLP-114 Implanter Tool
DLP-114 Surgical Kit
DLP-114 is used for maintenance treatment of schizophrenia in adult patients.
DLP-114 Implant Device is a drug-
device combination product intended 
to deliver risperidone for 6 months 
following subcutaneous implantation 
in the abdomen. The device comes 
in a vacuum-sealed vial and requires 
hydration prior to implantation.
DLP-114 Implanter Tool is 
used to insert DLP-114 Implant 
Device subcutaneously into the 
abdomen.
DLP-114 Surgical Kit contains 
all the supplies necessary 
to perform the implantation 
and/or explantation 
procedure.
Placement 
Guide
Cannula with
beveled edge
Depth
Indicator
Implanter Tool in 
unlocked position
Actuator
Titanium Reservoir
Vacuum-sealed vial
Membrane
Membrane
2

ADVERSE REACTIONS
DRUG INTERACTIONS
For Investigational Use Only
Common adverse reactions include somnolence, appetite increased, fatigue, rhinitis, upper 
respiratory tract infection, vomiting, coughing, urinary incontinence, saliva increased, 
constipation, fever, Parkinsonism, dystonia, abdominal pain, anxiety, nausea, dizziness, dry 
mouth, tremor, rash, akathisia, and dyspepsia.
 
To report SUSPECTED ADVERSE REACTIONS, contact Delpor, Inc. at 1-800-718-8120, or the 
FDA at 1-800-FDA-1088, or www.fda.gov/medwatch
• Due to CNS effects, use caution when administering with other centrally-acting drugs. 
	
Avoid alcohol.
• Due to hypotensive effects, hypotensive effects of other drugs with this potential may be 
enhanced.
• Effects of levodopa and dopamine agonists may be antagonized.
• Cimetidine and ranitidine increase the bioavailability of risperidone.
• Clozapine may decrease clearance of risperidone.
• Fluoxetine and paroxetine increase plasma concentrations of risperidone.
• Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone.
INDICATIONS FOR USE
DLP-114 is maintenance treatment of schizophrenia in adults
CONTRAINDICATIONS
Known hypersensitivity to the product
Important Safety Information
USE IN SPECIFIC POPULATIONS
• Nursing mothers should not breast feed.
3
DOSAGE INFORMATION
Implant Version
Total Risperidone
Targeted Dose
Alpha 4
360 mg
1.0 mg/day
Alpha 7
435 mg
1.0 mg/day

DO NOT administer DLP-114 in patients with the following conditions:
  •   A body mass index (BMI) outside of the ≥18.5≤ 40 kg/m2 inclusive range.
  •   Known hypersensitivity to titanium
  •   Known hypersensitivity or allergy to lidocaine or any local anesthetic agent of the 	
      amid type (local anesthetic used during implant and explant procedures)
  •   History of abnormal scar formation or family history of keloid formation
  •   Previously defined hypersensitivity to risperidone
  •   Tested positive for hepatitis B, hepatitis C or HIV infection
  •   History of clinically significant hypersensitivity or allergic reactions
  •   Used an investigational drug or device within 3 months prior to first dosing
  •   Pregnant or nursing
Take additional precautions for patients with the following condictions:
  • Cerebrovascular events, including stroke, in elderly patients with dementia-related     	
    psychosis. Risperidone is not approved for use in patients with dementia-related 	    	
    psychosis.
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesis
  • Hyperglycemia and diabetes mellitus
  • Hyperprolactinemia
  • Orthostatic hypotension
  • Leukopenia, Neutropenia, and Agranulocytosis: has been reported with 	
	
	
     antipsychotic. Patients with a history of a clinically significant low white blood cell              	
     count (WBC) or a drug-induced leukopenia/neutropenia should have their complete    	
     blood count (CBC) monitored frequently during the first few months of therapy and    	
     discontinuation should be considered at the first sign of a clinically significant   	            	
     decline in WBC in the absence of other causative factors.
  • Potential for cognitive and motor impairment
  • Seizures
  • Dysphagia
  • Priapism
  • Disruption of body temperature regulation
  • Antiemetic Effect
  • Suicide
  • Increased sensitivity in patients with Parkinson’s disease or those with dementia 		
     with Lewy bodies
  • Diseases or conditions that could affect metabolism or 	hemodynamic responses
WARNINGS AND PRECAUTIONS
!
4

Ti
Indicates the manufacturer’s catalog number so 
that the medical device can be identified.
Indicates the manufacturer’s batch code so that 
the batch or lot can be identified.
Indicates the manufacturer’s serial number so 
that a specific medical device can be identified.
Indicates the date after which the medical device 
is not to be used.
Indicates the number of units in the associated 
packaging.
Indicates a medical device that has been sterilized 
using radiation.
Requires a prescription to use in the United 
States.
Indicates the need for the user to consult the 
instructions for use.
Indicates a medical device that is non-pyrogenic
Indicates the product contains titanium
Indicates a medical device that is intended for 
one use, or for use on a single patient during a 
single procedure
Indicates the temperature to which the medical 
device can be safely exposed
Indicates a medical device that should not be 
used if package has been damaged or opened
Indicates a medical device that needs to be 
protected from moisture
Indicates the need for the user to consult the 
instructions for use for important cautionary 
information such as warnings and precautions
Indicates the medical device manufacturer
5
Catalog Number
Batch Code
Serial Number
Use By
Quantity
Sterilized using 
irradiation
Prescription only
Consult instructions 
for use
Non pyrogenic
Contains titanium
Do not reuse
Storage temperature 
range
Do not use if package 
is damaged
Keep dry
Attention: read all pre­
cautions and warnings in 
instructions for use
Manufacturer
ISO 15223-1, 
Clause 5.1.6 
ISO 15223-1
Clause 5.1.5 
ISO 15223-1
Clause 5.1.7 
ISO 15223-1
Clause 5.1.4 
ISO 15223-1
ISO 15223-1
Clause 5.2.4 
21 CFR 801.15 
(c)(1)(i)(F)
ISO 15223-1
Clause 5.4.3 
ISO 15223-1
Clause 5.6.3 
ISO 15223-1
ISO 15223-1
Clause 5.4.2 
ISO 15223-1
Clause 5.3.7 
ISO 15223-1
Clause 5.2.8
ISO 15223-1
Clause 5.3.4
ISO 15223-1
Clause 5.4.4
ISO 15223-1
Clause 5.1.1
Symbols Glossary
Standard 
Reference
Symbol Title
Explanatory Text
Symbol

6
Supplies
Box 1
Box 2
Box 3
Marking pen
Marking stencil
Alcohol prep swabs
Non-fenestrated drape
ChloraPrep Triple Swabstick
Fenestrated drape
20 Ga x 0.5” needle
Syringe, 30mL
Lidocaine hydrochloride USP 2%
25 Ga x 1.5” needle
Scalpel (size 15)
Adson tissue forceps
Hemostat forceps
Gauze sponges
Suture with needle
Needle driver
Transparent field dressing
Liquid adhesive
Wound Closure Strips
Allis grasping forceps
Implant Device in vacuum-sealed vial
50 mL saline vial
Alcohol swabs
60 mL syringe
20G x 0.5” needle
Venting needle
Implanter tool
a.
b.
c.
d.
e.
f.
g.
h.
i.
j.
k.
l.
m.
n.
o.
p.
q.
r.
s.
t.
a.
b.
c.
d.
e.
f.
a.
a.
g.
n.
s.
a.
a.
b.
c.
d.
e.
t.
o.
p.
q.
r.
h.
i.
j.
k.
l.
m.
b.
c.
d.
e.
f.
One box needed for each implant inserted
Implanter Tool
f.

Supplies: Box 2
Supplies: Box 1
Supplies: Box 3 and Hydrated Implant from Step 1
Supplies: Loaded Implanter Tool from Step 3
Supplies: Box 2
1. Hydrate Implant Device(s)
2. Prepare Implantation Site
3. Load Implanter Tool with Implant
4. Insert Implant(s)
5. Complete Procedure
Implant Device needs to be hydrated with sterile 
saline at least 10 minutes and up to 4 hours before 
implantation. This step activates the release of the drug.
Below is a high level overview of the steps you will take when implanting the device. Please follow the 
Implantation Procedure detailed instructions starting on page 9.
Implant Device is implanted under the skin in 
the abdomen greater than 5 cm away from the 
midline and greater than 5 cm below the ribcage 
(either on the right of left side of the patient).
The hydrated Implant Device is removed from the 
vial and placed in the cannula of the implanter tool.
The loaded Impanter Tool is used to insert the implant 
device subcutaneously in the abdomen. Multiple implants 
must be inserted in a fan shape through a single incision.
Sutures are used to close the incision after the 
implant(s) have been inserted. 
Implantation Procedure Overview
7

IMPLANTATION PROCEDURE 
Delpor

IMPLANTATION PROCEDURE 
1.1   Prepare saline vial
1.2   Fill hydration syringe
1 Hydrate Implant
a.  Carefully open the Implant Device kit
     (Box 2) and remove all contents from
     the box.
b.  Remove flip cover on saline vial to
     expose vial septum.
c.   Swab septum with alcohol prep swab.
a.  Insert venting needle into saline vial.
b.  Use included needle and syringe to
     draw 50 mL of saline from the
     swabbed vial.
c.  Ensure no air bubbles in syringe
     by tapping syringe with needle
      pointed up to loosen bubbles, and
      depress syringe plunger until fluid
     comes out.
9
a.
a.
50 mL
b.
c.
b.
i
SUPPLIES NEEDED FOR THIS STEP (BOX 2):
- 50 mL saline vial
- Implant Device in vacuum-sealed vial
- 60 mL syringe
- 20G x 0.5needle
- Alcohol swabs
- Venting needle

1.3   Inject saline into implant vial
1.4   Repeat for all implants
a.  Lay the DLP-114 implant vial on a flat
     surface so that the device inside is
     horizontal.
b.  Penetrate the vial’s septum with the
     saline filled syringe, taking care not to
     strike the device with the needle. Allow
     the saline to be drawn into the vial.
c.  Once no more saline is being drawn into
      the vial, pull needle out of implant vial.
a.  Confirm patient’s dosage and
     repeat implant hydration steps
     (1.1- 1.3) for the total number of
     implants the patient requires.
d.  Check implant is properly submerged.
      Make sure air bubble is no bigger than 
     the red window on vial label.
e.  Stand vial upright for at least 10
     minutes, but no more than 4 hours.
CAUTION: The implant device has 
white membranes at either end, which 
should remain undamaged for proper 
drug delivery. Hydrate the implant 
vial in a horizontal position to ensure 
that the needle cannot reach the 
membrane 
CAUTION: To ensure proper vacuum 
and seal integrity, DO NOT use vial if 
there is a bubble that exceeds the red 
outline on the vial label OR if implant 
is not fully submerged in saline.
!
!
10
b.
d.
e.
Air bubble should 
not be bigger than 
red window
Inject while horizontal
Do not hit 
membrane
Repeat Steps 
1.1 - 1.3 for 
all implants
10+ minutes
Delpor

IMPLANTATION PROCEDURE 
2.1   Position the patient
2.2   Mark implantation site
2 Prepare Implantation Site
a.  Have patient lie on back. 
a.  Use marking pen and stencil to draw
     lines to indicate the implantation site(s)
     and incision. Stencil should be placed
     greater than 5 cm away from the ribs and
     greater than 5 cm from the midline.
b.  Up to 3 implants, each represented by a
      solid line, can be implanted through a
     single incision in a fan-shaped layout as
     described by the stencil.
CAUTION: Take care to implant 
greater than 5 cm away from the 
midline to avoid damaging superficial 
epigastric arteries. Consider patient 
lifestyle habits (such as belt line) for 
additional implant location guidance.
!
Possible Implantation Areas - Implant 
either to the left or right of midline
Implantation Site
Incision
11
i
SUPPLIES NEEDED FOR THIS STEP (BOX 1):
- Marking pen
- Marking Stencil
- Alcohol swabs
- 30 mL syringe
- Hemostat forceps
- Adson tissue forceps
- Scalpel
- ChloraPrep swabstick
- Non-fenestrated drape
- Lidocaine HCl 2%
   with epinephrine
- Fenestrated drape
- 25G x 1.5” needle
- 20G x 0.5” needle

2.4   Wash hands
2.6    Lay out surgical instruments
i
NOTE: Assistance is required to remove packaging as needed throughout the 
procedure. Have the assistant open any packaging, and use sterile technique to 
retrieve the contents.
2.5   Put on latex-free sterile gloves
a.  Perform proper surgical hand scrub.
a.  Perform appropriate hand hygiene
     technique and put sterile gloves on
      both hands. 
a.  Using proper aseptic technique, remove remaining items from surgical kit (Box 1)
     and arrange on sterile field drape. 
CAUTION: Surgical kit box and all packaging are NOT sterile and SHOULD NOT 
be placed onto sterile field drape.
!
12
Delpor
2.3   Clean site
Antiseptic
a.  Use alcohol swab or other antiseptic to
     perform first cleaning of implantation site.

IMPLANTATION PROCEDURE 
2.7   Clean implantation site
a.  Using repeated back-and-forth strokes, swab
the implantation site with a Chloraprep
swabstick for  30 seconds before letting
the site air dry for 30 seconds. If the
implantation site is moist, increase swab
time to 2 minutes and air dry for 1 minute.
b.  Drape patient’s abdomen with fenestrated
      drape.
a.
b.
13

2.8   Apply anesthetic
i
RECOMMENDATION: It is recommended that local anesthesia is applied following the 
procedure described below, but the method of application is at the discretion of the 
health care provider.
a.  At the end of the marked line(s) closer to
     the patient’s midline, use scalpel to make
     a single 5mm incision. Take care to cut
     only through the dermis.
a.  Starting at one end of the marked line,
      insert entire length of needle along the 
      marked line.
c.  Determine that anesthesia is adequate.
      10mL of lidocaine is recommended for
      complete anesthetization of each
      marked track.
d.  Repeat steps for each implant
b.  Slowly pull the needle out while depressing
     syringe to inject lidocaine. Anesthetization 
     of the implantation site(s) and incision site
     may be performed with two or three 
     needle reentries.
2.9   Make incision at an angle
14
Inject Lidocaine along
implantation path
Make incision at 
an angle
cross-sectional view
Delpor
b.
CAUTION: Check for any known allergies to lidocaine before injecting anesthetic. 
i
NOTE: Up to 3 implants can be inserted 
through a single incision, following the 
fan-shaped pattern described by the 
provided stencil.
!

IMPLANTATION PROCEDURE 
i
NOTE: Use a technique called tenting to visibly raise the skin when performing 
pocket-making or insertion procedures to ensure correct subcutaneous 
placement of the implant, “just under the skin”. 
a.  Lift the edge of the incision with Adson
      tissue forceps. Use blunt end of closed
     hemostat forceps (curved end up) to
     create pocket (about 1 to 3 mm) using
     blunt dissection - keeping curved end of
     forceps up. Slide hemostat forceps back
     and out of the pocket.
b.  Repeat 2.10 as needed to create
     additional pockets for each additional
     implant.
2.10   Use hemostat tip as dilator to deepen the pocket.
15
Repeat step 2 for all implants

16
3 Load Implant Device
b.  Confirm that cannula of implanter tool is
     fully extended, and that actuator is in its
     most forward position.
a.  Remove implanter tool from packaging
      (Box 3) and place on sterile field drape.
3.2   Check implanter tool position
a.  After implant has been hydrating in 
     vial for 10 minutes, remove vial’s 
     rubber stopper.
b.  Pour implant onto gauze pad
      within sterile field. The implant can
      then be handled with sterile gloves
      or forceps.
3.1   Pour contents of implant vial onto 
        sterile area and retrieve implant
Gauze pad
Sterile field drape
a.  Use forceps to insert and slide 
implant into end of cannula.
c.  Set aside within sterile field while
     preparing insertion site.
b.  Push implant until it stops. The 
beveled end of the cannula will 
prevent the membrane from 
being punctured. 
3.3   Load implant in cannula using
        aseptic techniques
Implant
Cannula
a.
b.
Delpor
i
SUPPLIES NEEDED FOR THIS STEP (BOX 1, BOX 3):
- Gauze pads
- Hydrated Implant Device from Step 1
- Implanter Tool (Box 3)

IMPLANTATION PROCEDURE 
4.1 Insert cannula tip
4
Implant Insertion into Site
a.  Grasp handle of implanter
     tool and rest index finger on
     back of actuator.
b.  Make sure cannula bevel is
      up. While lifting edge of
      incision with Adson forceps,
      insert cannula tip with a slight
      twist.
17
i
RECOMMENDATION: Use your 
free hand to palpate and guide the 
insertion.
Cannula bevel
Depth indicator
Actuator
i
SUPPLIES NEEDED FOR THIS STEP:
- Loaded Implanter Tool from Step 3
- Adson tissue forceps
4.2  Slide cannula through the pocket 
CAUTION: Keep implanter steady.
DO NOT push implant into muscle tissue.
!
a.  The cannula tip should be slightly tilted upward
     so that the skin will be visibly raised (tented)
     at all times during insertion. This ensures
     deployment is in the subcutaneous space.
b.  Use other hand to stretch skin in the same
      direction as the intended insertion path
      Advance cannula subcutaneously along
      implantation line until cannula depth indicator
      reaches incision.
Depth indicator

4.3  Deploy implant
a.  Hold implanter tool in position and
     slide actuator back until it stops with
      a click. Ensure the implant is
      released fully from the cannula. 
b.  Gently press on deployed implant 
     and carefully withdraw implanter 
     tool from incision.
c.  Palpate the marked track site
     to ensure the implant has been
     placed correctly under the skin. 
CAUTION: DO NOT move implanter 
tool until actuator is fully retracted 
with a click, to ensure correct 
positioning of the implant.
!
i
NOTE: When the cannula is retracted and 
in the locked position, the sharp protection 
feature is deployed (safe mode).
Sharp 
protection 
feature
a.
b.
18
Delpor

19
IMPLANTATION PROCEDURE 
4.4  Insert additional implants if required:
a.  Fully extend cannula and ensure that
      actuator is titled in its most forward position.
b.  Repeat the prior two steps for each
      additional implant (Step 9 - Load Cannula,
      and Step 10 - Implant Insertion into site).
i
RECOMMENDATION: The second or 
third implant can be inserted through 
the same incision and positioned in a 
fan-shaped layout.
To insert second implant, 
repeat Steps 4.
Additional Implant
First Implant

20
5.2   Close incision
a.  After removing implanter tool,
     press sterile gauze to the wound to
      stop the bleeding.
b.  Clean insertion area using aseptic
     technique.
c.  Close incision using the provided
     sutures and needle driver.
d.  Cover incision with transparent field
      dressing and gauze sponges.
e.  Wait a few minutes before leaving
     patient’s bedside to make sure
     there are no signs of bleeding.
a.
b.
c.
d.
Delpor
5.1  Discard implanter tool and vial
           in biohazard container.
5
Complete Procedure
- 20G x 0.5” needle
i
SUPPLIES NEEDED FOR THIS STEP (BOX 1):
- Gauze sponges
- Liquid adhesive
- Suture
- Needle driver
- Transparent field dressing
- Wound closure strips

21
IMPLANTATION PROCEDURE 
5.3   After-procedure care
a.  Patient should keep insertion site clean
     and dry for 24 hours.
b.  Patient should avoid heavy lifting and
      strenuous physical activity for 48 hours.
c.  Make follow-up appointment to
     check the incision site after 14 days. 
     If the incision has healed, remove
     sutures and apply liquid adhesive.
     After 30 seconds of drying the liquid
     adhesive, apply wound closure strips.
d.  Inform patient to call their healthcare
      provider for any questions or concerns.

EXPLANT PROCEDURE 
i
Delpor
NOTE: A new surgical kit will be used to 
perform explant and replacement procedures.

EXPLANT PROCEDURE 
1.1   Wash hands
1.2   Put on latex-free gloves
1.3  Locate implant
1
Prepare Explant Site
a.  Perform proper surgical hand scrub.
a.  Inspect site by palpating location of implant
b.  Mark position of the implant(s) with marking
     pen.
a.  Perform appropriate hand hygiene
     technique and put sterile gloves on
     both hands
CAUTION: If unable to palpate the
implant(s) prior to removal, do not
attempt removal. Refer to a radiologist 
to help locate the implant. Attempt 
removal only after the depth and
location of the implant can be 
determined.
!
23
i
SUPPLIES NEEDED FOR THIS STEP (BOX 1):
- Marking pen
- 20G x 0.5” needle
- Lidocaine HCl 2% with epinephrine
- 25G x 1.5” needle
- Antiseptic
- Fenestrated drape
- 30 mL syringe

1.4  Clean removal site
1.5 Apply anesthetic
a.  Using repeated back-and-forth strokes, swab
     the implantation site with ChloraPrep for 30
     seconds before letting the site air dry for 30
      seconds. If the implantation site is moist, 
     increase swab time to 2 minutes and air dry 
     for 1 minute.
b.  Drape patient’s abdomen with fenestrated drape.
Inject Lidocaine along
implantation path
a.
b.
b.
c.
24
Delpor
i
RECOMMENDATION: It is recommended that local anesthesia is applied following the 
procedure described below, but the method of application is at the discretion of the 
health care provider.
a.  Starting at one end of the marked line,
      insert entire length of needle along the 
      marked line.
c.  Determine that anesthesia is adequate.
      10mL of lidocaine is recommended for
      complete anesthetization.
d.  Repeat steps for each implant.
b.  Slowly pull the needle out while depressing
     syringe to inject lidocaine. Anesthetization 
     of the implantation site(s) and incision site
     may be performed with two or three 
     needle reentries.
CAUTION: Take care not to puncture the 
implant membranes when inserting needle.
!
CAUTION: Check for any known allergies to lidocain before injecting anesthetic. 
!

EXPLANT PROCEDURE 
2.1   Make incision with forceps support
2.2   Remove Implant with grasping forceps
2
Remove Implant Device
a.  Using the flat face of the tip of the
     hemostat forceps, depress the skin just in
     front of the end of the implant device.
a.  Continue to push the implant towards
      the forceps. 
b.  Allis forceps may be used to pull out the
      implant. Be sure not to damage the
      membrane at the end of the implant to
      avoid additional exposure to drug.
b.  Use fingers from one hand to gently
      depress the forceps into the skin and use
      the thumb from the same hand to push
      the implant towards and over the forceps
      tenting the skin under the raised tip of
     the device. 
c.  Using the other hand make an incision at
     the tented end until the device is visible
     (the titanium/metallic finish makes it 
     easily distinguishable from tissue). Cut
     through the fibrous capsule if needed to
     release the end of the device.
CAUTION: Be careful not to nick the
implant membrane
!
25
b.
c.
i
SUPPLIES NEEDED FOR THIS STEP (BOX 1):
- Hemostat forceps
- Scalpel
- Allis grasping forceps

3.2   Following proper wound closing method, close the
       incision. The method of wound closing is at the
       discretion of the health care provider.
3
Complete Procedure
26
Delpor
3.1  Discard implant device in biohazard container.

For Investigational Use Only
Instructions for Use 
Risperidone Implant, DLP-114

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 100 of 101 
 
26.6 APPENDIX 6. DLP-114 Labels 
 

 
Study Protocol 
 
                                                                                     Protocol No.: DLP-114-03 
 
 
 
Delpor Inc 
Page 101 of 101