Randomized controlled study of the histamine H3 inverse agonist MK-0249 in adult attention-deficit/hyperactivity disorder.
BACKGROUND
It has been suggested that the histamine subtype 3 receptor inverse agonists such as MK-0249 might be effective in treating attention-deficit/hyperactivity disorder (ADHD). We evaluated the effects of MK-0249 in adults with ADHD.


METHODS
A randomized, double-blind, placebo-controlled, incomplete block, 2-period crossover study of MK-0249 5-10 mg/d and osmotic-release oral system (OROS) methylphenidate 54-72 mg/d (active comparator) was performed in 72 men and women aged ≥ 18 to ≤ 55 years who met DSM-IV criteria for ADHD of either inattentive or combined subtype and who had a chronic course of behavior disorder. The study was conducted from August 2007 through April 2008 at 6 US sites. Primary efficacy was assessed by the mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score after 4 weeks of treatment.


RESULTS
Change from baseline in AISRS at week 4 for MK-0249 was not different from placebo (P = .341), whereas a significant benefit was seen for OROS methylphenidate versus placebo (P < .001). Analysis of secondary end points, including the Conners Adult ADHD Rating Scales, showed results consistent with the AISRS. A similar percentage of patients reported adverse events for MK-0249 compared with placebo (73% versus 69%, respectively). However, a greater percentage of patients reported insomnia as an adverse event with MK-0249 treatment compared with placebo (32% versus 11%, respectively).


CONCLUSIONS
MK-0249 10 mg/d is not effective for the treatment of adult ADHD.


BACKGROUND
ClinicalTrials.gov identifier: NCT00475735.
Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, USA. william.herring@merck.com
W Joseph
WJ
Herring
Timothy E
TE
Wilens
Lenard A
LA
Adler
Christine
C
Baranak
Kenneth
K
Liu
Duane B
DB
Snavely
Christopher R
CR
Lines
David
D
Michelson
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D017442:Histamine Agonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008774:Methylphenidate / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D010552:Personality Assessment; D010865:Pilot Projects; D052999:Quinazolinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D055815:Young Adult
D017442:Histamine Agonists; C574738:MK-0249; D052999:Quinazolinones; D008774:Methylphenidate