A Study to Test the Safety and Efficacy of MK0249 in Patients With ADHD (0249-018)(COMPLETED)

A Phase IIa, Randomized, Double-Blind, Placebo-Controlled, Incomplete Block, Two-period, Crossover Clinical Trial to Study the Safety and Efficacy of MK0249, 10 mg, for Adult Patients, Ages 18 to 55, With Attention Deficit Hyperactivity Disorder (ADHD)

The purpose of this study is to investigate the safety and efficacy of an investigational treatment for Attention Deficit Hyperactivity Disorder (ADHD) when compared to placebo.

Study Overview

• Status: Completed
• Conditions: Attention-Deficit/Hyperactivity Disorder (ADHD)
• Intervention / Treatment: Drug: MK0249; Drug: Concerta (methylphenidate); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

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:

• Patient is between 18 and 55 years of age (inclusive)
• Patient is an adult with a current DSM-IV diagnosis of ADHD of inattentive or combined subtype, as assessed via a structured interview using the ACDS and AISRS
• Females of child-bearing potential must use acceptable methods of birth control during the study and for 1 month post-therapy

Exclusion Criteria:

• Patient has a history of a neurological disorder resulting in ongoing impairment
• Patient has a lifetime history of a psychotic disorder, bipolar disorder, or post-traumatic stress disorder
• Patient has evidence of ongoing depression
• Patient is sensitive or allergic to methylphenidate
• Patient has glaucoma
• Patient has a previous history of narrowing or blockage of the GI tract
• Patient has a history of a sleep disorder (e.g., insomnia, sleep apnea, nightmares, or night terrors) within 6 months prior to screening
• Patient has a history of a cardiovascular disorder within 6 months prior to screening
• Patient has moderate or severe persistent asthma
• Patient has a history of substance abuse or dependence not in sustained full remission for at least one year according to DSM-IV
• Patient has taken part in a research study within the past 30 days of signing informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-0249; Total time in the study will be ~10 weeks.	Drug: MK0249; MK-0249, 10 mg per day was taken orally daily. If patients were unable to tolerate 10 mg per day, they were allowed to titrate down to 5 mg per day.
Active Comparator: Concerta; Total time in the study will be ~10 weeks.	Drug: Concerta (methylphenidate); Titration of Concerta began with two 18-mg capsules (36 mg) for 3 consecutive days, followed by three 18-mg capsules (54 mg) for another 3 consecutive days, ending with four 18-mg capsules (72 mg) for the remainder of the treatment period. If patients were unable to tolerate 72 mg per day, they were allowed to titrate down to 54 mg per day. Concerta was taken orally once daily.; Other Names: CONCERTA®
Placebo Comparator: Placebo; Total time in the study will be ~10 weeks.	Drug: Placebo; For 4 of the 6 treatment sequences, patients had one 4-week treatment period with placebo of MK-0249 (tablets) and placebo of Concerta (capsules). For patients assigned to active treatments of MK-0249 or Concerta, in order to preserve the blind, placebo of the non-active component was provided, ie, if MK was assigned (tablets), then placebo of Concerta (capsules) was also provided. Each patient was to dose with tablets and capsules, either active or placebo. Placebo was taken orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in the Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (AISRS) Total Score After 4 Weeks of Treatment	The AISRS total score consists of 18 items from the original Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) which were derived based on Diagnostic and Statistical Manual-4 (DSM-IV) criteria for ADHD. The ADHD-RS include 9 items that address symptoms of inattention and 9 items that address symptoms of impulsivity and hyperactivity. Each item is rated from 0 to 3. The AISRS total score can range from 0 to 54. A higher score corresponds to a worse severity of ADHD.	after 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in the AISRS Inattentive Subscale Score After 4 Weeks of Treatment	The AISRS inattentive subscale score consists of 9 items from the original ADHD-RS which address inattention. Each item is rated from 0 to 3. The AISRS inattentive subscale score can range from 0 to 27. A higher score corresponds to a worse severity of ADHD inattentiveness. Data not reported due to failure of primary hypothesis and program termination.	after 4 weeks of treatment
>/= 30% AISRS Total Score Responder Rate After 4 Weeks of Treatment;	The AISRS total score consists of 18 items from the original ADHD-RS which were derived based on DSM-IV criteria for ADHD. The ADHD-RS include 9 items that address symptoms of inattention and 9 items that address symptoms of impulsivity and hyperactivity. Each item is rated from 0 to 3. The AISRS total score can range from 0 to 54. A higher score corresponds to a worse severity of ADHD. Data not reported due to failure of primary hypothesis and program termination.	after 4 weeks of treatment
>/=1-point Improvement in the CGI-S Score	The Clinical Global Impression - Severity of Illness Scale (CGI-S) is administered by a trained investigator who rates the severity of a patient's illness at the time of assessment, relative to the investigator's past experience with patients who have an ADHD diagnosis. The scores range from 1 to 7. Higher numbers correspond to more severe illness. Data not reported due to failure of primary hypothesis and program termination.	4 weeks of treatment
Mean Change From Baseline in the AISRS Hyperactive/Impulsive Subscale Score	The Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (AISRS) hyperactive/impulsive subscale score consists of 9 items from the original Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) which address hyperactivity and impulsivity. Each item is rated from 0 to 3. The AISRS hyperactive/impulsive subscale score can range from 0 to 27. A higher score corresponds to a worse severity of ADHD hyperactivity/impulsivity. Data not reported due to failure of primary hypothesis and program termination	4 weeks of treatment
Mean Change From Baseline in the Conners' Adult ADHD Rating Scale - Observer Screening Version (CAARS-O:SV) Total ADHD Symptom Score.	Conners' Adult ADHD Rating Scale - Observer Screening version (CAARS-O: SV) evaluates DSM-IV-oriented inattention, impulsivity and hyperactivity as well as measures of self-concept. It is a 30-item scale administered by a trained investigator or rater with "cue" questions. Each item is scored from 0 to 3 with higher scores corresponding to worse symptoms. The total score can range from 0 to 90. Data not reported due to failure of primary hypothesis and program termination.	4 weeks of treatment
Mean Change From Baseline in the Clinical Global Impressions-severity of Illness Scale(CGI-S) Score	The Clinical Global Impression - Severity of Illness Scale (CGI-S) is administered by a trained investigator who rates the severity of a patient's illness at the time of assessment, relative to the investigator's past experience with patients who have an ADHD diagnosis. The scores range from 1 to 7. Higher numbers correspond to more severe illness. Data not reported due to failure of primary hypothesis and program termination.	4 weeks of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline AISRS	Baseline values for all treatment groups are equal because the constrained longitudinal data analysis (cLDA) model was used (Liang and Zeger, 2000, Sankhyā: The Indian Journal of Statistics, Series B 62, 134-148).	Baseline

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Herring WJ, Wilens TE, Adler LA, Baranak C, Liu K, Snavely DB, Lines CR, Michelson D. Randomized controlled study of the histamine H3 inverse agonist MK-0249 in adult attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2012 Jul;73(7):e891-8. doi: 10.4088/JCP.11m07178.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: May 17, 2007
• First Submitted That Met QC Criteria: May 17, 2007
• First Posted (Estimate): May 21, 2007

Study Record Updates

• Last Update Posted (Estimate): July 28, 2015
• Last Update Submitted That Met QC Criteria: July 21, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; 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; Methylphenidate
• Other Study ID Numbers: 0249-018; 2007_519