Study to Assess the Safety and Efficacy of NRP104 in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)

A Phase III, Randomized, Double-Blind, Multi-Center, Placebo-Controlled, Parallel-Group, Forced Dose Titration, Safety and Efficacy Study of NRP104 in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)

The purpose of this study is to evaluate the safety and effectiveness of NRP104 administered as a daily morning dose (30, 50, and 70mg/day) compared to placebo in adults (18-55 years of age inclusive) diagnosed with moderate to severe Attention Deficit Hyperactivity Disorder (ADHD).

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder; Attention Deficit Disorders With Hyperactivity; Attention Deficit Hyperactivity Disorders
• Intervention / Treatment: Drug: NRP104

Detailed Description

This study is a randomized, phase III, multi-center, placebo-controlled, parallel-group, forced dose titration in which adult subjects (18-55 years of age inclusive) with ADHD will be randomized to NRP104 (30, 50, or 70 mg) or placebo for four weeks of double-blind evaluation of safety and efficacy.

The study will have three phases: (1) screening and washout; (2) baseline; and (3) 4-week double-blind evaluation of NRP104 and placebo. The double-blind period will include a forced dose titration phase followed by a fixed dose phase. Subjects will be required to visit the site up to 6 times over a 5-8 week period, or longer in cases requiring a 28-day wash out.

Screening and Washout: Subjects will be screened to establish eligibility for study participation. The Screening Visit (Visit 1) may take place over multiple days if needed to accommodate the subject's schedule. Those subjects who meet eligibility requirements will undergo medication washout, if applicable. The length of the ADHD medication washout period will range from 7-28 days.

Baseline: Following medication washout, subjects will return to the clinic for reassessment of eligibility criteria and establishment of baseline measures. The interval between the first day of the Screening Visit (informed consent date) and the Baseline Visit (Visit 2) must not exceed 35 days. Eligible subjects with a baseline ADHD-RS score greater than or equal to 28 (performed using adult DSM-IV prompts) will be randomized to treatment.

Double-blind treatment: Eligible subjects will be randomly assigned (in a 2:2:2:1 ratio of each of the three active doses vs. placebo) to a daily morning dose of NRP104 or placebo for 4 weeks. All NRP104 groups will start at a dose of 30 mg/day. Subjects randomized to 70 mg will be titrated to that dose over a 2-week period; those randomized to 50 mg will be titrated to that dose over a 1-week period; and those randomized to 30 mg will begin dosing on 30 mg per day during week one and will remain on that dose throughout the study. Double-blind assessment of the safety and efficacy of NRP104 will proceed for 4 weeks with weekly clinic visits scheduled for evaluations and medication disbursement.

Follow-up period: Subjects who have completed at least 2 weeks of double-blind participation, will have the option to continue participation in an open-label extension study (Protocol NRP104.304: one-year safety study). Subjects who are not eligible or who choose not to participate in the extension study will continue to be followed for thirty days following their last dose of study drug. A telephone contact (or contact in person) will be initiated by the research site to collect any new or ongoing SAEs and to follow-up on any unresolved or related AEs from the Final Study Visit or Early Termination (ET) Visit (Visit 6). If the Principal Investigator determines AEs are not acceptably resolved, appropriate follow-up should continue until all safety concerns, in the opinion of the Investigator, are resolved.

• Study Type: Interventional
• Enrollment (Actual): 420
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Study Centers, LLC
  • California
    • El Centro, California, United States, 92243
      • Valley Clinical Research, Inc.
    • Irvine, California, United States, 92612
      • University of California, Irvine Child Development Center
    • LaFayette, California, United States, 94549
      • Bay Area Research Institute
    • Rolling Hills Estate, California, United States, 90274
      • Peninsula Research Associates
    • San Francisco, California, United States, 94143
      • University of California, San Francisco, Dept. of Psychiatry
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Alpine Clinical Research Center
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University School Of Medicine
    • New London, Connecticut, United States, 06320
      • Psychiatric Medicine Center
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Clinical Research Center
    • Miami, Florida, United States, 33173
      • Miami Research Associates
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc.
    • Tampa, Florida, United States, 33606
      • Meridien Research
    • West Palm Beach, Florida, United States, 33407
      • Janus Center for Psychiatric Research LLC
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Northwest Behavioral Research Center
    • Smyrna, Georgia, United States, 30080
      • Carman Research
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Psychiatric Associates
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Johns Hopkins at Green Spring Station
    • Rockville, Maryland, United States, 20852
      • Marc Hertzman, MD
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02138
      • Massachusetts General Hospital
  • Michigan
    • Flint, Michigan, United States, 48507
      • Summit Research Network (Michigan) Inc.
    • Rochester Hills, Michigan, United States, 48307
      • Rochester Center for Behavioral Medicine
  • Missouri
    • St Charles, Missouri, United States, 63301
      • St Charles Psychiatric Associates-Midwest Research
    • St. Louis, Missouri, United States, 63141
      • Mercy Health Research
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center for Psychiatry and Behavioral Medicine
  • New Jersey
    • Clementon, New Jersey, United States, 08021
      • CNS Research Institute (CRI)
  • New York
    • New York, New York, United States, 10010
      • VA NY Harbor Healthcare System
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University ADHD Program
    • Raleigh, North Carolina, United States, 27609
      • Richard Weisler and Associates
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland, Case Western Reserve University
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
  • Oregon
    • Portland, Oregon, United States, 97210-2659
      • Oregon Center for Clinical Investigations, Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19149
      • Cns Research Institute, P.C.
  • Texas
    • Austin, Texas, United States, 78756
      • FutureSearch Trials
    • Bellaire, Texas, United States, 77401
      • Claghorn-Lesem Research Clinic
    • Houston, Texas, United States, 77007
      • Bayou City Research
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates, P.A.
    • Lake Jackson, Texas, United States, 77566
      • R/D Clinical Research, Inc.
    • Lubbock, Texas, United States, 79423
      • John M. Turnbow, MD, PA
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The Clinical Study Center
    • Woodstock, Vermont, United States, 05091
      • Neuropsychiatric Associates
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Psychiatric Alliance of the Blue Ridge Clinical Research
    • Herndon, Virginia, United States, 20170
      • Neuroscience, Inc.
    • Virginia Beach, Virginia, United States, 23452
      • Brighton Research Group
  • Washington
    • Seattle, Washington, United States, 98104
      • Summit Research Network LLC (Seattle)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be 18-55 years of age, inclusive.
• Must be male or non-pregnant female. Females of childbearing potential (FOCP) must use contraception.
• Must have a medical assessment with no clinically significant or relevant abnormalities as determined by medical history, PE, clinical and lab evaluation.

• Must have 12-lead ECGs defined by the following parameters:

  1. QT/QTcF interval < 450 msec for males and < 470 msec for females
  2. Resting heart rate is between 40 and 100 beats per minute
  3. P-R interval < 200 msec
  4. QRS interval <110 msec.
• Meets Diagnostic and Statistical Manual of Mental Disorders Fourth Edition; Text Revision (DSM-IV-TR™) criteria for a primary diagnosis of ADHD (diagnostic code 314.00 and 314.01) established by a psychiatric evaluation that reviews DSM-IV-TR™ criteria with at least 6 of the 9 subtype criteria met. The Adult ADHD Clinical Diagnostic Scale (ACDS v1.2) will be utilized as the diagnostic tool.
• Has a baseline ADHD-RS score greater than or equal to 28 assessed using adult DSM-IV prompts.
• Understands and is able, willing, and likely to fully comply with the study procedures and restrictions.
• Has given written 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 procedures.

Exclusion Criteria:

• In the opinion of the investigator, the subject is significantly underweight [e.g., Body Mass Index (BMI) < 18.5] or morbidly obese.
• Has any comorbid psychiatric diagnosis with significant symptoms such as any severe comorbid Axis II disorders or severe Axis I disorders including Post Traumatic Stress Disorder (PTSD), psychosis, bipolar illness, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder or other symptomatic manifestations that will contraindicate NRP104 treatment or confound efficacy or safety assessments. Specifically, subjects with mild to moderate forms of Axis I disorders including social phobia and dysthymia may be included while subjects with a lifetime history of psychosis or bipolar disorder will be excluded from participation. Comorbid psychiatric diagnoses will be established by a psychiatric evaluation that includes the Structured Clinical Interview for DSM-IV-TR™ disorders (SCID-I) interview at the screening visit.
• 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 with mental retardation or a severe learning disability are excluded.
• Has a history of seizure (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or family history of Tourette's Disorder.
• Has a known cardiac structural abnormality or any other condition that may affect cardiac performance.
• Has any clinically significant ECG or laboratory abnormality at Screening or Baseline.
• Subject has a history of hypertension or has a resting sitting systolic blood pressure > 139mmHg or diastolic blood pressure > 89mmHg.
• Has used any prohibited medication except for ADHD medications within 30 days of screening visit. Hormonal contraceptives are acceptable.
• Has a documented allergy, intolerance, or documented history of non-responsivity to methylphenidate or amphetamine.
• Currently has (or had a history within the last 6 months of) a drug dependence or substance abuse disorder according to DSM-IV-TR™ criteria (excluding nicotine) as established by a SCID-I at the screening visit.
• Has a positive urine drug result at Screening (with the exception of subject's current stimulant therapy, if any) or at Baseline.
• Has taken an investigational drug or taken part in a clinical trial within 30 days prior to Screening.
• The female subject is pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinician-administered ADHD-rating scale (ADHD-RS) performed using adult DSM-IV prompts	weekly over a period of 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The Clinical Global Impression of Improvement (CGI-I)	4 times over a period of 4 weeks
Self-report of the Pittsburgh Sleep Quality Index (PSQI) measured at Baseline and at the Final Study Visit	twice over a period of 4 weeks
Occurrence of treatment-emergent adverse events and specific evaluation of blood pressure, heart rate, electrocardiogram (ECG), laboratory findings, and physical examination (PE)	4 weeks

Collaborators and Investigators

• Sponsor: New River Pharmaceuticals

Publications and helpful links

General Publications

• Surman CB, Roth T. Impact of stimulant pharmacotherapy on sleep quality: post hoc analyses of 2 large, double-blind, randomized, placebo-controlled trials. J Clin Psychiatry. 2011 Jul;72(7):903-8. doi: 10.4088/JCP.11m06838.
• Adler LA, Goodman DW, Kollins SH, Weisler RH, Krishnan S, Zhang Y, Biederman J; 303 Study Group. Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2008 Sep;69(9):1364-73. doi: 10.4088/jcp.v69n0903. Epub 2008 Sep 9.
• Mattingly GW, Weisler RH, Young J, Adeyi B, Dirks B, Babcock T, Lasser R, Scheckner B, Goodman DW. Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. BMC Psychiatry. 2013 Jan 29;13:39. doi: 10.1186/1471-244X-13-39.
• Babcock T, Dirks B, Adeyi B, Scheckner B. Efficacy of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder previously treated with amphetamines: analyses from a randomized, double-blind, multicenter, placebo-controlled titration study. BMC Pharmacol Toxicol. 2012 Dec 19;13:18. doi: 10.1186/2050-6511-13-18.
• Waxmonsky JG, Waschbusch DA, Glatt SJ, Faraone SV. Prediction of placebo response in 2 clinical trials of lisdexamfetamine dimesylate for the treatment of ADHD. J Clin Psychiatry. 2011 Oct;72(10):1366-75. doi: 10.4088/JCP.10m05979pur.
• Adler LA, Weisler RH, Goodman DW, Hamdani M, Niebler GE. Short-term effects of lisdexamfetamine dimesylate on cardiovascular parameters in a 4-week clinical trial in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2009 Dec;70(12):1652-61. doi: 10.4088/JCP.09m05335pur.
• Adler LA, Goodman D, Weisler R, Hamdani M, Roth T. Effect of lisdexamfetamine dimesylate on sleep in adults with attention-deficit/hyperactivity disorder. Behav Brain Funct. 2009 Aug 3;5:34. doi: 10.1186/1744-9081-5-34.

Helpful Links

• FDA Recall Information
• FDA-approved Label

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Study Completion (Actual): November 1, 2006

Study Registration Dates

• First Submitted: June 7, 2006
• First Submitted That Met QC Criteria: June 7, 2006
• First Posted (Estimate): June 8, 2006

Study Record Updates

• Last Update Posted (Estimate): July 2, 2009
• Last Update Submitted That Met QC Criteria: July 1, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: Attention Deficit Hyperactivity Disorder; Attention Deficit Disorders with Hyperactivity; Attention Deficit Hyperactivity Disorders
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Disease; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: NRP104.303