Clinical trial NCT00337285: An Open-label Study of NRP104 in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Attention Deficit Hyperactivity Disorder
Attention Deficit Disorders With Hyperactivity
Attention Deficit Hyperactivity Disorders
Keywords: Attention Deficit Hyperactivity Disorder
Attention Deficit Disorders with Hyperactivity
Attention Deficit Hyperactivity Disorders
Lead sponsor: New River Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Shire
First posted: 2006-06-15
Enrollment: 349
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in ADHD-RS-IV Total Score From Baseline at Up to One Year
timeFrame: up to one year
Secondary outcomes:
measure: Number of Participants With Improvement on CGI-I
timeFrame: Up to 1 year
measure: Change in PSQI Total Score From Baseline at Up to One Year
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Clinical Study Centers, LLC
state: Arkansas
city: El Centro
country: United States
facility: Valley Clinical Research, Inc.
state: California
city: Irvine
country: United States
facility: University of California, Irvine Child Development Center
state: California
city: LaFayette
country: United States
facility: Bay Area Research Institute
state: California
city: Rolling Hills Estate
country: United States
facility: Peninsula Research Associates
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco, Dept. of Psychiatry
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Boulder
country: United States
facility: Alpine Clinical Research Center
state: Colorado
city: New London
country: United States
facility: Psychiatric Medicine Center
state: Connecticut
city: Fort Myers
country: United States
facility: Gulfcoast Clinical Research Center
state: Florida
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: West Palm Beach
country: United States
facility: Janus Center for Psychiatric Research LLC
state: Florida
city: Roswell
country: United States
facility: Northwest Behavioral Research Center
state: Georgia
city: Smyrna
country: United States
facility: Carman Research
state: Georgia
city: Overland Park
country: United States
facility: Psychiatric Associates
state: Kansas
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Lutherville
country: United States
facility: Johns Hopkins at Green Spring Station
state: Maryland
city: Rockville
country: United States
facility: Marc Hertzman, MD
state: Maryland
city: Cambridge
country: United States
facility: Masschusetts General Hospital
state: Massachusetts
city: Flint
country: United States
facility: Summit Research Network (Michigan) Inc.
state: Michigan
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine
state: Michigan
city: St Charles
country: United States
facility: St Charles Psychiatric Associates-Midwest Research
state: Missouri
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine
state: Nevada
city: Clementon
country: United States
facility: CNS Research Institute (CRI)
state: New Jersey
city: New York
country: United States
facility: VA New York Harbor Healthcare System
state: New York
city: Durham
country: United States
facility: Duke University ADHD Program
state: North Carolina
city: Raleigh
country: United States
facility: Richard Weisler and Associates
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Portland
country: United States
facility: Oregon Center for Clinical Investigations, Inc.
state: Oregon
city: Philadelphia
country: United States
facility: CNS Research Institute, P.C.
state: Pennsylvania
city: Austin
country: United States
facility: FutureSearch Trials
state: Texas
city: Bellaire
country: United States
facility: Claghorn-Lesem Research Clinic
state: Texas
city: Houston
country: United States
facility: Bayou City Research
state: Texas
city: Houston
country: United States
facility: Red Oak Psychiatry Associates, P.A.
state: Texas
city: Lake Jackson
country: United States
facility: R/D Clinical Research, Inc.
state: Texas
city: Lubbock
country: United States
facility: John M. Turnbow, MD, PA
state: Texas
city: Burlington
country: United States
facility: The Clinical Study Center
state: Vermont
city: Woodstock
country: United States
facility: Neuropsychiatric Associates
state: Vermont
city: Charlottesville
country: United States
facility: Psychiatric Alliance of the Blue Ridge Clinical Research
state: Virginia
city: Herndon
country: United States
facility: NeuroScience, Inc.
state: Virginia
city: Virginia Beach
country: United States
facility: Brighton Research Group
state: Virginia
city: Seattle
country: United States
facility: Summit Research Network LLC (Seattle)
state: Washington
Study officials:
affiliation: Massachusetts General Hospital
name: Joseph Biederman, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ginsberg L, Katic A, Adeyi B, Dirks B, Babcock T, Lasser R, Scheckner B, Adler LA. Long-term treatment outcomes with lisdexamfetamine dimesylate for adults with attention-deficit/hyperactivity disorder stratified by baseline severity. Curr Med Res Opin. 2011 Jun;27(6):1097-107. doi: 10.1185/03007995.2011.567256. Epub 2011 Mar 28.
citation: Mattingly G, Weisler R, Dirks B, Babcock T, Adeyi B, Scheckner B, Lasser R. Attention deficit hyperactivity disorder subtypes and symptom response in adults treated with lisdexamfetamine dimesylate. Innov Clin Neurosci. 2012 May;9(5-6):22-30.