PMID- 23920422
OWN - NLM
STAT- MEDLINE
DCOM- 20140519
LR  - 20181202
IS  - 1878-5506 (Electronic)
IS  - 1389-9457 (Linking)
VI  - 14
IP  - 10
DP  - 2013 Oct
TI  - Alertness and psychomotor performance effects of the histamine-3 inverse agonist 
      MK-0249 in obstructive sleep apnea patients on continuous positive airway 
      pressure therapy with excessive daytime sleepiness: a randomized adaptive 
      crossover study.
PG  - 955-63
LID - S1389-9457(13)00150-0 [pii]
LID - 10.1016/j.sleep.2013.04.010 [doi]
AB  - OBJECTIVES: We aimed to evaluate the efficacy of the selective H3 receptor 
      inverse agonist MK-0249 to treat excessive daytime sleepiness (EDS). METHODS: In 
      this three-period, double-blind, crossover study, 125 patients (100 men, 25 
      women; mean age, 48.6 years) with obstructive sleep apnea receiving nasal 
      continuous positive airway pressure therapy who had refractory EDS were 
      randomized to 2 weeks each of daily MK-0249 (5, 8, 10, or 12 mg, adaptively 
      assigned), modafinil 200 mg, and placebo. At baseline and after each treatment 
      period, six maintenance of wakefulness tests (MWT) and Psychomotor Vigilance 
      Tasks (PVT) were conducted at 2-h intervals, beginning 1h postdose ( approximately 09:00). The 
      Epworth sleepiness scale (ESS), Clinical Global Impression of Severity (CGIS) and 
      Digit Symbol Substitution Test (DSST) also were assessed. The primary end point 
      was MWT sleep latency averaged over the first four time points (MWT-early). 
      RESULTS: MWT-early mean change from baseline sleep latency at week 2 was 1.2 min 
      for placebo, 2.1 min for MK-0249 (top two doses pooled; P>.05 vs. placebo), and 
      5.9 min for modafinil (P < or = .001 vs. placebo). MK-0249 showed improvements vs 
      placebo on secondary and exploratory end points of ESS, CGIS, PVT, and DSST. 
      Insomnia adverse events (AEs) were greater for MK-0249 (combined doses, 17.5%) 
      than for placebo (0.9%) or modafinil (1.8%). CONCLUSION: MK-0249 did not 
      significantly affect MWT sleep latency. However, the pattern of improvement on 
      subjective ratings and psychomotor performance end points suggested that MK-0249 
      was associated with changes in aspects of cognition and performance not captured 
      by the MWT.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Herring, W Joseph
AU  - Herring WJ
AD  - Merck Sharp and Dohme Corp., Whitehouse Station, NJ, USA. Electronic address: 
      william.herring@merck.com.
FAU - Liu, Kenneth
AU  - Liu K
FAU - Hutzelmann, Jill
AU  - Hutzelmann J
FAU - Snavely, Duane
AU  - Snavely D
FAU - Snyder, Ellen
AU  - Snyder E
FAU - Ceesay, Paulette
AU  - Ceesay P
FAU - Lines, Christopher
AU  - Lines C
FAU - Michelson, David
AU  - Michelson D
FAU - Roth, Thomas
AU  - Roth T
LA  - eng
SI  - ClinicalTrials.gov/NCT00620659
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130803
PL  - Netherlands
TA  - Sleep Med
JT  - Sleep medicine
JID - 100898759
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Histamine Agonists)
RN  - 0 (MK-0249)
RN  - 0 (Quinazolinones)
RN  - 0 (Wakefulness-Promoting Agents)
RN  - R3UK8X3U3D (Modafinil)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Benzhydryl Compounds/administration & dosage
MH  - Combined Modality Therapy
MH  - *Continuous Positive Airway Pressure
MH  - Cross-Over Studies
MH  - Disorders of Excessive Somnolence/*drug therapy/therapy
MH  - Double-Blind Method
MH  - Female
MH  - Histamine Agonists/*administration & dosage
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Modafinil
MH  - Psychomotor Performance/*drug effects
MH  - Quinazolinones/*administration & dosage
MH  - Sleep Apnea, Obstructive/*drug therapy/therapy
MH  - Treatment Outcome
MH  - Wakefulness/*drug effects
MH  - Wakefulness-Promoting Agents/administration & dosage
MH  - Young Adult
OTO - NOTNLM
OT  - Excessive daytime sleepiness
OT  - Histamine subtype-3 receptor
OT  - MK-0249
OT  - Modafinil
OT  - Obstructive sleep apnea
OT  - Randomized trial
EDAT- 2013/08/08 06:00
MHDA- 2014/05/20 06:00
CRDT- 2013/08/08 06:00
PHST- 2012/11/08 00:00 [received]
PHST- 2013/03/20 00:00 [revised]
PHST- 2013/04/11 00:00 [accepted]
PHST- 2013/08/08 06:00 [entrez]
PHST- 2013/08/08 06:00 [pubmed]
PHST- 2014/05/20 06:00 [medline]
AID - S1389-9457(13)00150-0 [pii]
AID - 10.1016/j.sleep.2013.04.010 [doi]
PST - ppublish
SO  - Sleep Med. 2013 Oct;14(10):955-63. doi: 10.1016/j.sleep.2013.04.010. Epub 2013 
      Aug 3.