Clinical trial NCT02139111: PRC-063 in Adolescent ADHD
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm, Multi-Center Study Measuring the Efficacy and Safety of PRC-063 in Adolescent ADHD Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ADHD
Lead sponsor: Rhodes Pharmaceuticals, L.P.
Sponsor class: INDUSTRY
Collaborators: name: Purdue Pharma LP
First posted: 2014-05-15
Enrollment: 360
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this randomized, placebo-controlled, double-blind, parallel group study is to evaluate the clinical efficacy and safety of PRC-063 in adolescents with ADHD.

Detailed description: This study is a randomized, phase III, multicenter, placebo-controlled, parallel-group, forced-dose titration in which adolescent subjects (12 to 17 years of age inclusive) with ADHD will be randomized to PRC-063 (25, 45, 70 or 85 mg) or placebo for four weeks of double-blind evaluation of safety and efficacy. The study will have four phases: (1) screening and 1-week washout; (2)baseline and double-blind, forced-dose titration over a 2-week period; (3) double-blind evaluation over a 2-week period; and (4) a 14-day safety follow-up. Subjects will be required to visit the site 6 times over a 5 week period.

Screening and Washout: Subjects will be screened to establish eligibility for study participation. Subjects who meet eligibility requirements will undergo ADHD medication washout, if applicable.

Eligibility criteria: Inclusion Criteria:

* Must be male or non-pregnant female at least 12 years of age and less than 18 years of age.
* Must have an ADHD diagnosis, in attentive, hyperactive/impulsive or combined, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) based on clinician assessment using multiple informants and a structured interview.
* Must be unsatisfied with his or her current pharmacological therapy for treatment of ADHD or not currently receiving pharmacological therapy for ADHD. Inclusion of subjects naïve to pharmacological therapy for ADHD is permitted.
* Female subjects must be one of the following: a. surgically sterile prior to screening; b. if of childbearing potential, abstinent or willing to use a reliable method of contraception, such as oral contraceptive, two barrier methods, a barrier method plus a spermicidal agent.
* Female subjects of Child-Bearing Potential (FOCP) must be a negative serum β-hCG pregnancy test at screening.
* Must have a minimum level of intellectual functioning, as determined by an Intelligence Quotient (IQ) score of 80 or above based on the WASI or the KBIT.
* Mentally and physically competent to sign an informed assent document, in the case of the subject, and an informed consent document, in the case of the parent/guardian, indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
* Able and willing to comply with the study procedures for the entire length of the study, including a successful swallow test of an empty 85 mg capsule.
* Total score of 24 or greater on the clinician-rated ADHA-5-RS, as assessed at Visit 2

Exclusion Criteria:

* Having an allergy to methylphenidate or amphetamines or a history of serious adverse reactions to methylphenidate.
* Known to be non-responsive to methylphenidate treatment. Non-response is defined as methylphenidate use at various doses for a phase of at least four weeks at each dose with little or no clinical benefit.
* Being diagnosed with or having a history of strokes, epilepsy, migraine headaches (greater than 1 instance every two months), glaucoma, thyrotoxicosis, tachyarrhythmias or severe angina pectoris or have serious or unstable medical illness. Subjects with controlled or stable asthma or diabetes will be permitted.
* Elevated blood pressure, defined as any values above 89 diastolic or 139 systolic, as assessed at Visit 1.
* Clinically significant ECG abnormalities, as assessed at Visit 1.
* Clinically significant laboratory abnormalities, as assessed at Visit 1.
* Currently receiving guanethidine, pressor agents, MAO inhibitors, coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), phenylbutazone, tricyclic antidepressants (e.g., imipramine, desipramine), selective serotonin reuptake inhibitors (SSRIs) or herbal remedies (unless on a stable dose for 4 weeks).
* Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary heart disease, transient ischemic attack or stroke or other serious cardiac problems that may place the subject at increased vulnerability to the sympathomimetic effects of a stimulant drug.
* Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
* Subjects who are currently considered a suicide risk by the investigator.
* Having a primary diagnosis of schizophrenia, schizoaffective disorder, primary affective disorder, schizotypal personality, major depression, bipolar disorder, generalized anxiety, borderline personality disorder, antisocial personality or another unstable psychiatric condition requiring treatment, as assessed by the structured interview conducted at Visit 1.
* Having a history or suspected physiological dependence (excluding nicotine) on narcotic analgesics or other psychoactive drugs (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines).
* Excessive consumption of alcohol (consumes alcohol in quantities greater than 15 drinks per week; 1 drink is defined as 360 mL/12 oz. of beer, 120 mL/4 oz. of wine, or 30 mL/1 oz. of hard liquor), or history (within previous 6 months) of alcohol abuse.
* Currently (or within 30 days before the planned start of treatment) receiving an investigational drug or using an experimental medical device.
* Homeless.

Primary outcomes:
measure: Change from Baseline in Clinician-administered ADHD-5-Rating Scale
timeFrame: Baseline week 2, weeks 3-6
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: National City
country: United States
facility: Synergy Clinical Research
state: California
city: Newport Beach
country: United States
facility: Newport Beach Clinical Research Associates, Inc.
state: California
city: Orange
country: United States
facility: Orange County Neuro Phychiatry Research Centre
state: California
city: Bradenton
country: United States
facility: Florida Clinical Research Center
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Research
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: CNS Healthcare Jacksonville
state: Florida
city: Maitlin
country: United States
facility: Florida Clinical Research Center
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: Boise
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine Inc.
state: Nevada
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions Inc.
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Clinical Trials, L.P.
state: Texas
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, L.P.
state: Texas
city: Houston
country: United States
facility: Bayou City Research Ltd
state: Texas
city: Houston
country: United States
facility: Red Oak Psychiatry Associates
state: Texas
city: Houston
country: United States
facility: Houston Clinical Trials
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: Clinton
country: United States
facility: Ericksen Research
state: Utah
city: Salt Lake City
country: United States
facility: Physiciatric and Behavioral Solutions
state: Utah
city: Herndon
country: United States
facility: NeuroScience
state: Virginia
city: Bellvue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Kirkland
country: United States
facility: Eastside Therapeutic Resource
state: Washington
city: Calgary
country: Canada
facility: Mathison Centre for Mental Health Research and Education
state: Alberta
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Chokka Center for Integrative Health
state: Alberta
city: Vancouver
country: Canada
facility: Dr. Margaret Weiss
state: British Columbia
city: Dartmouth
country: Canada
facility: Atlantic ADHD Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Niagra Falls
country: Canada
facility: Doctors Jackiewicz Professional Medical Corporation
state: Ontario
city: Ottawa
country: Canada
facility: Dr. Judy van Stralen
state: Ontario
city: Toronto
country: Canada
facility: Stress, Trauma, Anxiety, Rehabilitation and Treatment (START) in the Mood and Anxiety Disorders Clinic
state: Ontario
city: Whitby
country: Canada
facility: The Kids Clinic
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital Saskatoon
state: Saskatchewan
Study officials:
affiliation: Purdue Pharma LP
name: Joseph Reiz
role: STUDY_DIRECTOR
References:
citation: Weiss MD, Surman C, Khullar A, Owens J, He E, Cataldo M, Donnelly G. Effect of a Multilayer, Extended-Release Methylphenidate Formulation (PRC-063) on Sleep in Adolescents with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Fixed-Dose, Placebo-Controlled Trial Followed by a 6-Month Open-Label Follow-Up. J Child Adolesc Psychopharmacol. 2021 Nov;31(9):623-630. doi: 10.1089/cap.2021.0087. Epub 2021 Oct 28.
citation: Weiss MD, Cutler AJ, Kollins SH, Donnelly GAE. Efficacy and Safety of a Long-Acting Multilayer-Release Methylphenidate Formulation (PRC-063) in the Treatment of Adolescent Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Clinical Trial with a 6-Month Open-Label Extension. J Child Adolesc Psychopharmacol. 2021 Nov;31(9):610-622. doi: 10.1089/cap.2021.0034. Epub 2021 Oct 8.