Clinical trial NCT04507204
Conditions: Attention-Deficit/Hyperactivity Disorder
Keywords: ADHD Methylphenidate Adhansia XR MPH OROS Phase IV
Sponsor: Purdue Pharma LP
Start date: 2020-07-30; Completion date: 2022-01-31
Enrollment: 267 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to investigate the treatment effectiveness of Adhansia XR at month-2 after initiation, and the effectiveness of Adhansia XR overall and when compared with the active comparator group (Concerta) over time.

Detailed description:
This phase IV study is a prospective, open-label, randomized, pragmatic study to investigate the treatment effectiveness of Adhansia XR at Month-2 after initiation, and the effectiveness of Adhansia XR overall and when compared with the active comparator group (OROS MPH or Concerta) over time. Additional outcome assessments for both treatment arms include Health-Related Quality of Life (HRQoL) during the 6-month follow-up period. The burden of illness (BOI) will be investigated by collecting additional measures such as healthcare resource utilization (HCRU), broader treatment patterns, and comorbidities.

Arms: arm 1: Adhansia XR capsules taken orally once daily with or without food. arm 2: Concerta tablets taken orally once daily in the morning and swallowed whole with the aid of liquids, with or without food.
Interventions: intervention 1: Adhansia XR intervention 2: Concerta
Intervention descriptions: intervention 1: Methylphenidate extended-release capsules taken once daily (25 mg, 35 mg, 45 mg, 55 mg, 70 mg, and 85 mg) intervention 2: An osmotic-controlled oral release delivery system (OROS) of methylphenidate HCl (MPH) extended-release tablets taken once daily (18 mg, 27 mg, 36 mg, and 54 mg)

Protocol documents:
Prot_SAP_002.pdf: 
Official Title: Real-world Evidence of Duration of Adhansia XR for Treatment of ADHD (RE-
DAX): An Open-label Pragmatic Study to Assess the Real-world Effectiveness of Adhansia XR 
in Treatment of Adult and Adolescent Patients with ADHD in the United States 
 
NCT #: NCT04507204 
 
Date of Document: April 14, 2020 




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Adhansia XR RE-DAX Study 
v2.0 dated 14 APRIL 2020 
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ADHD. Thus, the RE-DAX study plans to investigate the treatment effectiveness of Adhansia XR at 
Month-2 after initiation, and the effectiveness of Adhansia XR overall and when compared with the 
active comparator group (OROS MPH or Concerta) over time. Additional outcome assessments for 
both treatment arms include Health-Related Quality of Life (HRQoL) during the 6-month follow-up 
period. The burden of illness (BOI) will be investigated by collecting additional measures such as 
healthcare resource utilization (HCRU), broader treatment patterns, and comorbidities. 
Objectives: 
Primary Objectives 
•
To assess the real-world (RW) effectiveness of Adhansia XR among adolescent and adult patients
diagnosed with ADHD, by comparing the total score results of the ADHD-Rating Scale 5 (ADHD-
RS-5) at Month-2 to the baseline visit among patients receiving Adhansia XR
Secondary Objectives 
•
To compare the effectiveness of Adhansia XR with the active comparator group among adolescent
and adult patients diagnosed with ADHD, measured by the Time-Sensitive ADHD Symptom Scale
(TASS), completed at the end of waking hours (14 – 16 hours post-dosing) at Month-2 after the
baseline visit
•
To describe the RW effectiveness of Adhansia XR among adolescent and adult patients diagnosed
with ADHD, measured by the Clinical Global Impression-Severity (CGI-S), Clinical Global
Impression-Improvement (CGI-I), and Treatment Satisfaction Questionnaire for Medication
(TSQM); including results from the TASS and ADHD-RS-5 at other collected time points
compared to the baseline visit
•
To describe the RW effectiveness of the active comparator medication among adolescent and adult
patients diagnosed with ADHD, measured by the CGI-S, CGI-I, TSQM, and ADHD-RS-5;
including results from the TASS at other collected time points compared to the baseline visit
•
To describe the safety events and safety event rates related to Adhansia XR and the active
comparator
•
To describe HCRU between patients in the Adhansia XR and active comparator groups
•
To describe HRQoL outcomes between patients in the Adhansia XR and active comparator groups,
measured by the Adult ADHD QoL (AAQoL-R) - Revised 


Adlon Therapeutics L.P., a subsidiary of Purdue Pharma L.P. 
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•
To describe the treatment patterns for ADHD patients in this study, including but not limited to
dose modifications of study treatment or changes in concomitant medications
•
To describe the BOI of patients in the Adhansia XR and active comparator groups
•
To describe patient sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) in the
Adhansia XR and active comparator groups
Study design: The RE-DAX study is a phase IV, prospective, randomized, open-label pragmatic study 
comparing outcomes of adolescent and adult patients diagnosed with ADHD treated with Adhansia 
XR or the active comparator (OROS MPH or Concerta). The RE-DAX study will be conducted in 
approximately 34 sites in the US, with approximately 200 patients (100 adults, 100 adolescents) 
randomized (1:1) to each treatment group. The enrollment period will be approximately 6 months, and 
per patient follow-up will also be approximately 6 months, from the study enrollment date of the last 
patient until treatment discontinuation, lost to follow-up, withdrawal of consent, death, or end of 
follow-up (whichever occurs first). After the patients are screened for eligibility and provide consent 
(and assent, if appropriate), they will be randomized 1:1 to the Adhansia XR or the active comparator 
group, and baseline questionnaires and assessments will be collected. The titration period (conducted 
per standard of care [SoC]), is estimated to take place over 8 weeks or less to achieve optimal ER 
MPH dosing; hence the primary comparisons occurring at Month-2 compared to baseline. Patients will 
receive prescriptions for study treatment for up to 6 months to be obtained from a retail pharmacy per 
SoC. Both the data from healthcare provider (HCP) visits and patient-reported outcomes (PROs) will 
be collected and recorded in an electronic data capture (EDC) system. PROs will be completed by the 
patient or parent/guardian approximately every 1 month during follow-up, while HCP study visits 
should occur at screening/baseline, and through follow-up at Month-2, -4, and -6.  
Study population: Patients who fulfill the following eligibility criteria will be asked to provide 
informed consent (and assent, if appropriate): 
Inclusion criteria 
1. Patient with a physician-confirmed diagnosis of ADHD per Diagnostic and Statistical Manual of
Mental Disorders (DSM-5) criteria, and the HCP has made the decision to prescribe an ER MPH
product to the patient for potential improvement of symptoms throughout and later in the day,
independent of this study


Adlon Therapeutics L.P., a subsidiary of Purdue Pharma L.P. 
Adhansia XR RE-DAX Study 
v2.0 dated 14 APRIL 2020 
Protocol/Study No.: ADA4003 
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•
Note: The specific DSM-5 criteria satisfied by each patient enrolling will be collected, in addition
to the primary reason for starting on an ER MPH treatment.
2. Patient must be 12 years of age or older
3. Patient must be an appropriate patient to receive Adhansia XR or OROS MPH (or Concerta)
according to the US product labels; a patient must be appropriate and willing to receive either drug,
as randomization will assign them to a specific treatment group. Patient may be treatment-
experienced or naïve to pharmacological therapy for ADHD, so long as all inclusion and no
exclusion criteria are met.
4. Patient must be willing to take only the assigned study medication per HCP instructions based on
FDA label guidance for treatment of their ADHD for the first 2 months of the study (i.e., full
titration period). Subjects should not be on any other medication, or starting any new non-
medication treatment, proven to have effect on ADHD in the first two months of the study.
Exclusion criteria 
1. Concurrent participation in an investigational study in which patient assessment and/or treatment
may be dictated by a protocol
2. Patient with a true allergy to MPH, amphetamines (AMP) or sympathomimetic amines, history of
serious adverse reactions to MPH or AMP or be known to be non-responsive to MPH or AMP
treatment
3. Patient is adequately treated for ADHD on current treatment, and change to a long-acting
methylphenidate does not offer a predictable benefit
4. Female patients of child bearing potential who are pregnant, planning on becoming pregnant or
breastfeeding
5. Patient with any known conditions that are contraindicated for either Adhansia XR or OROS MPH
(or Concerta) use, as documented in the US Full Prescribing Information, including patients with
any known serious structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmias, or
coronary artery disease
•
Refer to the US label/prescription insert for more details on contraindications.
6. Patients with a known sensitivity to the food dye tartrazine (Federal Food, Drug, and Cosmetic
Yellow No. 5)


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v2.0 dated 14 APRIL 2020 
Protocol/Study No.: ADA4003 
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7. Suicidal Ideation
•
The Columbia-Suicide Severity Rating Scale (C-SSRS) will be administered at screening and
at Month-2, Month-4, and Month-6 but also depends on the judgment of the HCP.
8. Inability or unwillingness of the patient (or parent/guardian if patient is a minor) to complete the
study-required electronic questionnaires and provide required information through electronic
means
Data collection/Data Sources: The RE-DAX study will collect baseline medical history information 
and prospectively collect primary data from both healthcare providers (HCPs) and patients/parents using 
an electronic platform via a website-based system. The RE-DAX study sites will be responsible for 
enrolling patients, obtaining informed consent, administering HCP questionnaires, and entering data. 
An electronic case report form (eCRF) will be used to collect data required to address the study 
objectives. All RE-DAX study data collected from the HCPs will be entered into the eCRF by the site 
Investigator, or designee. The site Investigator, or designee, will be responsible for ensuring that the 
required retrospective data (e.g., comorbidities, ADHD treatment history) from the medical chart is 
extracted and all the prospective data for each patient is collected and all data is entered into the EDC 
system correctly. Once a patient has been screened and consents (and assents, if appropriate) to 
participate in the RE-DAX study, there will be a baseline assessment prior to starting study drug at the 
randomization visit (baseline). After the baseline assessment, HCPs will continue to treat and clinically 
manage patients according to SoC; study visits have been aligned with expected HCP encounters. PROs 
will be completed by the patient outside of the HCP visit schedule on an approximately monthly basis 
using a mobile application or website-based system; however, some PROs may be administered more 
(or less) often and are shown in the schedule of assessments (SoAs). Follow-up will continue for 6 
months until treatment discontinuation, patient withdrawal, lost to follow-up, death or end of study 
(whichever is first).  
Data Management and Quality Assurance: 
A data management plan will be created before data collection begins and will describe all functions, 
processes, and specifications for data collection, cleaning and validation. High data quality standards 
will be maintained, and processes and procedures utilized to repeatedly ensure that the data are as clean 
and accurate as possible when presented for analysis. Data quality will be enhanced through a series of 
programmed data quality checks that automatically detect out-of-range or anomalous data. Remote and 
on-site monitoring will be performed to examine compliance with the protocol and adherence to the data 


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collection procedures, to assess the accuracy and completeness of submitted clinical data, and to verify 
that records and documents are being properly maintained for the duration of the study. The monitor 
will perform source data verification by review of original patient records. 
Safety: All adverse events (AEs), regardless of relationship to the study treatment or intervention, will 
be monitored and reported throughout the entire course of the study. The AE reporting period begins 
when the patient is included into the study (date of first signature of informed consent and assent, if 
appropriate) and continues through the follow-up period. All AE verbatim terms will be recorded and 
coded using the Medical Dictionary for Regulatory Activities (MedDRA). AEs assessed as non-serious 
will be reported through the 7 days following the patient’s last study drug dose. Serious AEs (SAEs) 
that are ongoing at the patient’s last study visit must be followed until resolution or for 30 days after the 
patient’s last study drug dose, whichever comes first. Additional details will be described in the study 
Safety Monitoring Plan (SMP). 
Statistical Considerations: All computations and generation of tables, listings and data for figures 
will be performed using SAS® version 9.2 or higher (SAS Institute, Cary, NC, USA). Adult and 
adolescent patient treatment groups will be analyzed separately, but pooling of the age groups may be 
considered if appropriate. Descriptive analyses will be performed to gain an understanding of the 
qualitative and quantitative nature of the data collected, and the characteristics of the sample studied. 
Primary Objective Analysis: 
Primary treatment effectiveness will be determined by the mean improvement in ADHD symptoms 
based on the ADHD-RS-5 total score at Month-2 compared to baseline for Adhansia XR-treated 
patients. Note that the ADHD-RS-5 will also be collected for patients in the active comparator arm at 
the same time points but will be used for analysis of secondary objectives only. 
Secondary Objective Analyses: 
The key secondary purpose of the RE-DAX study is to compare effectiveness at Month-2 after the 
baseline visit between Adhansia XR and the active comparator, using the TASS questionnaire. The 
TASS will be completed at the end of waking hours (14 – 16 hours post-dosing) on a once monthly 
basis starting at Month-2. Patients will have the opportunity to complete the TASS each month within 
a 5-day window (excluding weekend days or holidays). A longitudinal regression approach such as 
linear mixed-model (LMM) or general estimating equation (GEE) will be used and fully described in 
the statistical analysis plan (SAP). Assessments of comparative effectiveness utilizing TASS will be 
performed at Month-2 through Month-6 during follow-up. Month-2 will be the key/primary 
comparison, with Month-3 through Month-6 as part of the secondary study objectives. 


Adlon Therapeutics L.P., a subsidiary of Purdue Pharma L.P. 
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v2.0 dated 14 APRIL 2020 
Protocol/Study No.: ADA4003 
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Further secondary outcomes will be analyzed to compare treatment groups, with appropriate 
prespecified tests of statistical significance. The analysis plan will be fully described in a written and 
approved SAP. 
Sample size 
The sample size is calculated for the key secondary purpose (effectiveness at Month-2 after the baseline 
visit between Adhansia XR and active comparator group, using the TASS questionnaire) to ensure 
adequate power for non-inferiority and superiority testing. A total sample size of 400 patients has been 
planned, with 200 patients in each treatment group and 200 patients within each age group. 
Randomization will be stratified by age group, with 100 adults and 100 adolescents per treatment group. 
Treatment group sizes of 80 patients per treatment group would be needed to achieve 81% power to 
detect non-inferiority using a one-sided, Mann-Whitney test assuming that the actual distribution is 
normal. The margin of non-inferiority is 6.60 points. The true difference between the score means is 
assumed to be null, with a significance level (alpha) of 0.05. The data are drawn from populations with 
Standard deviation (SD) of 16.0 points in each treatment group (calculated by PASS 11.0.4 Statistical 
Software. NCSS, LLC. Kaysville, Utah, USA. 2016). 
Thus, within each age category (adolescents and adults), 80 patients are needed in each treatment arm, 
plus 20% additional patients enrolled to account for assumed supplemental ADHD medication use 
after Month-2 and attrition. This results in a total of 96 patients in each treatment arm and each age 
category, or a total of 384 patients for the entire study. The planned sample size of 400 patients is 
adequately planned for 10% anticipated attrition, 10% exclusion for supplemental ADHD medication 
use after Month-2, and to sufficiently power the comparative analysis. 
Interim and Final Analyses: An abbreviated interim data look may be performed to assess overall 
data quality and completeness; it will not estimate primary or secondary outcomes. A final analysis 
report will be prepared at closure of the study database, when all data collection procedures are 
completed. The final report will encompass all planned analyses, including a description of the 
complete RE-DAX study population and patient outcomes, as described in the written SAP.  
Ethical and Regulatory Considerations: The RE-DAX study will be conducted in accordance with 
the protocol and all applicable laws and regulations including, but not limited to Good Clinical 
Practices (GCP), Good Pharmacoepidemiology Practices (GPP), the ethical principles that have their 
origins in the Declaration of Helsinki and applicable privacy laws. Data protection and privacy 
regulations will be strictly observed in capturing, forwarding, processing, and storing patient data. 
Every effort will be made to protect participant confidentiality according to the Directive 95/46/EC on 


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v2.0 dated 14 APRIL 2020 
Protocol/Study No.: ADA4003 
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the protection of individuals, and in compliance with Safe Harbor privacy principles. An Institutional 
Review Board/Independent Ethics Committee (IRB/IEC) must review and approve the protocol and 
informed consent form before any patients are enrolled. Before any protocol-directed data collection is 
performed, the patient must sign and date the IRB/IEC-approved informed consent form.