Randomized controlled trial of the CGRP receptor antagonist telcagepant for prevention of headache in women with perimenstrual migraine.
OBJECTIVE
The aim of this article is to evaluate the safety and efficacy of perimenstrual telcagepant, a CGRP receptor antagonist, for headache prophylaxis.


METHODS
We conducted a randomized, double-blind, placebo-controlled, six-month trial in women with migraine for ≥ 3 months who experienced perimenstrual headaches. Women were randomized to telcagepant 140 mg or placebo (2:1 ratio) for seven consecutive days perimenstrually. Safety was assessed by adverse events and laboratory tests. The primary efficacy endpoint was mean monthly headache days in the subset of women reporting perimenstrual migraine (-2 days to +3 days of menses onset) and ≥ 5 moderate or severe migraines per month prior to entering the trial.


RESULTS
Telcagepant was generally well tolerated: 66/2660 (2.5%) on telcagepant and 36/1326 (2.7%) on placebo discontinued because of a clinical adverse event. The percentages of patients with clinical adverse events, laboratory adverse events, or discontinuation because of a laboratory adverse event were also similar between treatments. Alanine aminotransferase elevations ≥ 3x normal occurred in 0.6% of women on telcagepant and 0.4% on placebo. Three women on telcagepant vs none on placebo had alanine aminotransferase elevations ≥ 8× normal. In the efficacy subset there was no significant effect of telcagepant (n = 887) vs placebo (n = 447) in mean monthly headache days (treatment difference -0.5 day (95% CI: -1.1, 0.1)). However, telcagepant was associated with a reduction in on-drug headache days (treatment difference -0.4 day (95% CI: -0.5, -0.2), nominal p < 0.001).


CONCLUSIONS
Telcagepant 140 mg taken perimenstrually for seven days was generally well tolerated, but was associated with transaminase elevations. Telcagepant did not reduce monthly headache frequency, but did reduce perimenstrual headaches.
Merck & Co. Inc, Department of Clinical Research, USA.
Tony W
TW
Ho
Merck & Co. Inc, Department of Clinical Research, USA.
Andrew P
AP
Ho
Merck & Co. Inc, Department of Clinical Research, USA.
Yang Joy
YJ
Ge
Merck & Co. Inc, Department of Clinical Research, USA.
Christopher
C
Assaid
Merck & Co. Inc, Department of Clinical Research, USA.
Regina
R
Gottwald
Barts Sexual Health Centre, St Bartholomew's Hospital, UK; Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, UK.
E Anne
EA
MacGregor
Headache Associates, USA.
Lisa K
LK
Mannix
Leiden University Medical Center, the Netherlands.
Willebrordus P J
WP
van Oosterhout
Merck & Co. Inc, Department of Clinical Research, USA.
Janelle
J
Koppenhaver
Merck & Co. Inc, Department of Clinical Research, USA.
Christopher
C
Lines
Leiden University Medical Center, the Netherlands.
Michel D
MD
Ferrari
Merck & Co. Inc, Department of Clinical Research, USA david.michelson@merck.com.
David
D
Michelson
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001381:Azepines / Q000627:therapeutic use*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008881:Migraine Disorders / Q000209:etiology / Q000517:prevention & control*; D011293:Premenstrual Syndrome / Q000150:complications*
D001381:Azepines; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007093:Imidazoles; C525458:telcagepant; D000410:Alanine Transaminase; D015740:Calcitonin Gene-Related Peptide
CGRP; Telcagepant; headache; menstrual; migraine; prophylaxis