Early-stage comparative effectiveness: Randomized controlled trial with histamine inverse agonist mk-7288 in excessive daytime sleepiness patients

Hong Sun, Catherine MacLeod, Kate Mostoller, Chantal Mahon, Lingling Han, John J. Renger, Junshui Ma, Kevin R. Brown, Valerie Schulz, Gary G. Kay, W. Joseph Herring, Christopher Lines, Laura B. Rosen, M. Gail Murphy, John A. Wagner

Research output: Contribution to journalArticlepeer-review

Abstract

Histaminergic neurons are regulators of the sleep.wake cycle. We evaluated the alerting effects of MK]7288 (10, 20 mg), a novel histamine]3 receptor inverse agonist (H3RIA), along with modafinil (200 mg), a standard treatment, in a randomized, double]blind, placebo controlled, crossover study of 56 patients with excessive daytime sleepiness (EDS). Efficacy was assessed using maintenance of wakefulness tests (MWT) and car driving simulation tests. MK]7288 and modafinil significantly prolongedMWTsleep latency (improvements vs. placebo of 8.1 to 8.2 min for MK]7288 and 10.2 min for modafinil), and improved car driving simulation standard deviation of lane position (reduction vs. placebo of 0.1m for each treatment). MK]7288 was associated with more insomnia (29%) than modafinil (9%) and placebo (6%). The study demonstrated the potential of the H3RIA mechanism for treating EDS, but did not show efficacy differentiation from modafinil. Early]stage comparative effectiveness can help prevent late]stage failure and increase the costeffectiveness of drug development.

Original languageEnglish (US)
Pages (from-to)1294-1302
Number of pages9
JournalJournal of Clinical Pharmacology
Volume53
Issue number12
DOIs
StatePublished - Dec 2013
Externally publishedYes

Keywords

  • Excessive daytime sleepiness
  • Histamine subtype-3 receptor
  • MK-7288, modafinil
  • Obstructive sleep apnea
  • Randomized trial

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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