An Open-label Study of NRP104 in Adults With Attention Deficit Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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The purpose of this study is to assess the long-term safety and efficacy of three NRP104 doses of 30 mg, 50 mg, or 70 mg, administered at the same time daily, in the treatment of adults with ADHD.

Detailed Description
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This is a multi-center, open-label, and single-arm study to assess the safety of three NRP104 doses (30 mg, 50 mg, or 70 mg per day) for up to one (1) year in the treatment of adults with ADHD. Subjects who were randomized and met all inclusion/exclusion criteria in Protocol NRP104.303 are eligible for participation in this protocol. The study will consist of three periods: a screening/baseline period, a 4-week dose titration, and a long-term maintenance of up to 11 months. There are three possibilities for subjects that rollover from the NRP104.303 protocol. They are: Subjects that rollover at the final visit of the NRP104.303 study (on the same day): The screening and baseline procedures from this open label study will coincide with the final study visit of Protocol NRP104.303. Subject data from final study visit will be transferred and utilized for the open label study. On this same day, the subject will be consented for NRP104.304, inclusion/exclusion criteria will be assessed, the subject will be enrolled, and study medication will be dispensed. Subjects that rollover not on the same day but within seven days of the NRP104.303 study: If the subject returns to enroll into the NRP104.304 study within seven days of the final NRP104.303 study visit and has not taken any excluded medications for which a washout is required, the final study visit procedures and data from the NRP104.303 study will be transferred and utilized for the screening and baseline visit procedures of this study, where applicable. When the subject returns to the site, they will be consented, inclusion and exclusion criteria will be assessed, the subject will be enrolled, and study medication will be dispensed. Subjects will require a full screening visit if more than 7 days have elapsed since they completed the NRP104.303 study: After screening results have been received by the site, the site personnel will contact the subject via telephone to inform them of continued study eligibility. During this call the subject will be instructed to stop all medications for the treatment of ADHD, if any. This call starts the washout of all psychoactive medications, which should last 7 (±2) days. During the Washout Phone Contact, the visit dates for the Baseline visit (Visit 01) and Visits 02 through 05 should be scheduled at 7-day intervals as calculated from Baseline. After the washout is complete, subjects will return to the clinic for the baseline visit (Visit 01) to have the baseline procedures performed and to receive study medication. Dose Titration All subjects will initiate treatment at NRP104 30 mg for the 1st week. At the subsequent 4 weekly visits (Visits 02, 03, 04, and 05), the subject's daily dose of NRP104 may be increased or decreased by 20 mg at weekly intervals to achieve the optimal efficacy and tolerability, if deemed appropriate by the Investigator. In this study, the maximum daily dose of NRP104 that can be received by the subject is 70 mg, and the minimum daily dose of NRP104 the subject must take to continue the treatment is 30 mg. Monthly Maintenance At the end of the initial 4-week dose titration (Visit 05), subjects will enter the long-term maintenance of up to 11 months. Monthly visits, starting with Visit 06, will have a window of ±4 days. All visits will be scheduled relative to the Baseline Visit date. The last scheduled visit of the protocol is Visit 16 at Month 12. During the long-term maintenance, the subject's dose may be increased or decreased by 20 mg at any visit, if deemed appropriate by the Investigator, to maintain optimal treatment in terms of efficacy and tolerability. All reasons for dose changes should be well documented by the investigator during the maintenance period. Subjects who cannot maintain the minimum daily dose of NRP 30 mg due to intolerance will be withdrawn from the study. Safety and Efficacy Assessments ADHD Rating Scale (ADHD-RS) performed using adult prompts and Clinical Global Impression (CGI) will be assessed by the Investigator. The Pittsburgh Sleep Quality Index (PSQI) will be assessed once every three months following baseline. Adverse events and concomitant medications will be recorded at each visit starting from the baseline visit. Vital signs will be measured at each visit from the screening visit. Physical exam and clinical laboratory tests (including pregnancy tests) will be assessed at Screening, Visit 10 and the final visit. Weight will be measured at the screening visit, baseline visit, and every month thereafter. Height will be measured at the screening visit and final visit. ECG parameters will be assessed at the screening visit, baseline visit, and every 3 months thereafter.

Official Title
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A Long-Term, Open-Label, and Single-Arm Study of NRP104 30 mg, 50 mg, or 70 mg Per Day in Adults With Attention Deficit Hyperactivity Disorder (ADHD)

Conditions
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Attention Deficit Hyperactivity Disorder, Attention Deficit Disorders With Hyperactivity, Attention Deficit Hyperactivity Disorders

Intervention / Treatment
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* Drug: Vyvanse (lisdexamfetamine dimesylate), NRP104


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be 18-55 years of age, inclusive, at the time of consent of the NRP104.303 study. Subject must have been randomized and must have met all inclusion/exclusion criteria in the NRP104.303 study. Subject must be male or non-pregnant female. Females of childbearing potential (FOCP) must comply with contraceptive restrictions noted in the protocol. Subject must have a satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, PE, clinical and laboratory evaluation. In the opinion of the investigator, the subject understands and is able, willing, and likely to fully comply with the study procedures and restrictions. Subject must have given written, personally signed and dated informed consent to participate in the study in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines and applicable regulations before completing any study specific procedures. Subject experienced no adverse events in a previous study of NRP104 or elsewhere that would preclude continued exposure to NRP104. Exclusion Criteria: Subject has any concurrent chronic or acute illness or unstable medical condition that could confound the results of safety assessments, increase risk to the subject or lead to difficulty complying with the protocol. Subjects who have a history of mental retardation or a severe learning disability are excluded. Subject has a known cardiac structural abnormality or any other condition that may affect cardiac performance. Subject has any clinically significant ECG or laboratory abnormality known to the investigator prior to dispensation of study medication. Subject has a resting sitting systolic blood pressure or diastolic blood pressure deemed clinically significant by the investigator. Subject has used any prohibited prescription medication except for medications used to treat ADHD within 30 days of screening visit. Hormonal contraceptives are acceptable. Subject has a positive urine drug result at Screening (with the exception of subject's current stimulant therapy, if any). Subject has taken an investigational drug or taken part in a clinical trial within 30 days prior to Screening (except for participating in an NRP104 study). The female subject is pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Vyvanse (lisdexamfetamine dimesylate), NRP104<br>* NRP104 capsule once-a-day orally beginning at 30mg/day and titrated by 20 mg per day at weekly intervals up to a maximum daily dose of 70 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ADHD-RS-IV Total Score From Baseline at Up to One Year | Change in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth edition (ADHD-RS-IV) total score from baseline. The ADHD-RS-IV consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54. | up to one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Improvement on CGI-I | Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement includes 1 and 2 on the scale. | Up to 1 year | 
| Change in PSQI Total Score From Baseline at Up to One Year | Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire consisting of 18 items which generates seven component scores on a scale from 0 (better sleep) to 3 (worse sleep) resulting in a global score of 0-21, where a higher number reflects worse sleep quality. | up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Attention Deficit Hyperactivity Disorder, Attention Deficit Disorders with Hyperactivity, Attention Deficit Hyperactivity Disorders