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Study to Assess the Safety and Efficacy of NRP104 in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)
This study has been completed.
First Received: June 7, 2006   Last Updated: July 1, 2009   History of Changes
Sponsor: New River Pharmaceuticals
Information provided by: New River Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00334880
  Purpose

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).


Condition Intervention Phase
Attention Deficit Hyperactivity Disorder
Attention Deficit Disorders With Hyperactivity
Attention Deficit Hyperactivity Disorders
Drug: NRP104
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by New River Pharmaceuticals:

Primary Outcome Measures:
  • Clinician-administered ADHD-rating scale (ADHD-RS) performed using adult DSM-IV prompts [ Time Frame: weekly over a period of 4 weeks ]

Secondary Outcome Measures:
  • The Clinical Global Impression of Improvement (CGI-I) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 4 weeks ]

Enrollment: 420
Study Start Date: May 2006
Study Completion Date: November 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00334880

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

Additional Information:
Publications:
Study ID Numbers: NRP104.303
Study First Received: June 7, 2006
Last Updated: July 1, 2009
ClinicalTrials.gov Identifier: NCT00334880     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by New River Pharmaceuticals:
Attention Deficit Hyperactivity Disorder
Attention Deficit Disorders with Hyperactivity
Attention Deficit Hyperactivity Disorders

Additional relevant MeSH terms:
Signs and Symptoms
Pathologic Processes
Disease
Attention Deficit Disorder with Hyperactivity
Mental Disorders
Nervous System Diseases
Mental Disorders Diagnosed in Childhood
Neurologic Manifestations
Attention Deficit and Disruptive Behavior Disorders
Hyperkinesis
Dyskinesias

ClinicalTrials.gov processed this record on November 30, 2009