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

Attention-Deficit/Hyperactivity Disorder (ADHD) Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00475735
• Other study ID #: 0249-018
• Secondary ID: 2007_519
• Status: Completed
• Phase: Phase 2
• First received: May 17, 2007
• Last updated: July 21, 2015
• Start date: July 2007
• Est. completion date: April 2008

Study information

• Verified date: July 2015
• Source: Merck Sharp & Dohme Corp.
• 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 investigate the safety and efficacy of an investigational treatment for Attention Deficit Hyperactivity Disorder (ADHD) when compared to placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention-Deficit/Hyperactivity Disorder (ADHD)
• Hyperkinesis

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Baseline AISRS	Baseline values for all treatment groups are equal because; the constrained longitudinal data analysis (cLDA) model was used; (Liang and Zeger, 2000, Sankhya: The Indian Journal of Statistics, Series B 62, 134-148).	Baseline	No
Primary	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	No
Secondary	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	No
Secondary	>/= 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	No
Secondary	>/=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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No