TY  - JOUR
PY  - 2013//
TI  - Early-stage comparative effectiveness: randomized controlled trial with histamine inverse agonist MK-7288 in excessive daytime sleepiness patients
JO  - Journal of clinical pharmacology
A1  - Sun, Hong
A1  - MacLeod, Catherine
A1  - Mostoller, Kate
A1  - Mahon, Chantal
A1  - Han, Lingling
A1  - Renger, John J.
A1  - Ma, Junshui
A1  - Brown, Kevin R.
A1  - Schulz, Valerie
A1  - Kay, Gary G.
A1  - Herring, W. Joseph
A1  - Lines, Christopher
A1  - Rosen, Laura B.
A1  - Murphy, M. Gail
A1  - Wagner, John A.
SP  - 1294
EP  - 1302
VL  - 53
IS  - 12
N2  - 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 prolonged MWT sleep 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 -0.1 m 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 cost-effectiveness of drug development.<p />  <p>Language: en</p>
LA  - en
SN  - 0091-2700
UR  - http://dx.doi.org/10.1002/jcph.182
ID  - ref1
ER  -