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

Attention Deficit Hyperactivity Disorder Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00334880
• Other study ID #: NRP104.303
• Status: Completed
• Phase: Phase 3
• First received: June 7, 2006
• Last updated: July 1, 2009
• Start date: May 2006
• Est. completion date: November 2006

Study information

• Verified date: July 2009
• Source: New River Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: November 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Disorders With Hyperactivity
• Attention Deficit Hyperactivity Disorder
• Attention Deficit Hyperactivity Disorders
• Disease
• Hyperkinesis

Intervention

Drug:
• NRP104

Locations

Country	Name	City	State
United States	FutureSearch Trials	Austin	Texas
United States	Claghorn-Lesem Research Clinic	Bellaire	Texas
United States	Alpine Clinical Research Center	Boulder	Colorado
United States	The Clinical Study Center	Burlington	Vermont
United States	Massachusetts General Hospital	Cambridge	Massachusetts
United States	Psychiatric Alliance of the Blue Ridge Clinical Research	Charlottesville	Virginia
United States	CNS Research Institute (CRI)	Clementon	New Jersey
United States	University Hospitals of Cleveland, Case Western Reserve University	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Duke University ADHD Program	Durham	North Carolina
United States	Valley Clinical Research, Inc.	El Centro	California
United States	Summit Research Network (Michigan) Inc.	Flint	Michigan
United States	Gulfcoast Clinical Research Center	Fort Myers	Florida
United States	NeuroScience, Inc.	Herndon	Virginia
United States	Bayou City Research	Houston	Texas
United States	Red Oak Psychiatry Associates, P.A.	Houston	Texas
United States	University of California, Irvine Child Development Center	Irvine	California
United States	Bay Area Research Institute	LaFayette	California
United States	R/D Clinical Research, Inc.	Lake Jackson	Texas
United States	Center for Psychiatry and Behavioral Medicine	Las Vegas	Nevada
United States	Clinical Study Centers, LLC	Little Rock	Arkansas
United States	John M. Turnbow, MD, PA	Lubbock	Texas
United States	Johns Hopkins at Green Spring Station	Lutherville	Maryland
United States	Miami Research Associates	Miami	Florida
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Psychiatric Medicine Center	New London	Connecticut
United States	VA NY Harbor Healthcare System	New York	New York
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Clinical Neuroscience Solutions, Inc.	Orlando	Florida
United States	Psychiatric Associates	Overland Park	Kansas
United States	Vince and Associates Clinical Research	Overland Park	Kansas
United States	CNS Research Institute, P.C.	Philadelphia	Pennsylvania
United States	Oregon Center for Clinical Investigations, Inc.	Portland	Oregon
United States	Richard Weisler and Associates	Raleigh	North Carolina
United States	Rochester Center for Behavioral Medicine	Rochester Hills	Michigan
United States	Marc Hertzman, MD	Rockville	Maryland
United States	Peninsula Research Associates	Rolling Hills Estate	California
United States	Northwest Behavioral Research Center	Roswell	Georgia
United States	University of California, San Francisco, Dept. of Psychiatry	San Francisco	California
United States	Summit Research Network LLC (Seattle)	Seattle	Washington
United States	Carman Research	Smyrna	Georgia
United States	Encompass Clinical Research	Spring Valley	California
United States	St Charles Psychiatric Associates-Midwest Research	St Charles	Missouri
United States	Mercy Health Research	St. Louis	Missouri
United States	Meridien Research	Tampa	Florida
United States	Brighton Research Group	Virginia Beach	Virginia
United States	Janus Center for Psychiatric Research LLC	West Palm Beach	Florida
United States	Neuropsychiatric Associates	Woodstock	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
New River Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Cl — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinician-administered ADHD-rating scale (ADHD-RS) performed using adult DSM-IV prompts		weekly over a period of 4 weeks
Secondary	The Clinical Global Impression of Improvement (CGI-I)		4 times over a period of 4 weeks
Secondary	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
Secondary	Occurrence of treatment-emergent adverse events and specific evaluation of blood pressure, heart rate, electrocardiogram (ECG), laboratory findings, and physical examination (PE)		4 weeks

External Links

•   FDA recall information