WHITEHOUSE STATION, N.J., Sept. 6, 2008 -
Merck & Co., Inc. today announced that in a Phase III clinical trial telcagepant (formerly known as MK-0974) – an investigational oral calcitonin gene-related peptide (CGRP) receptor antagonist – significantly relieved moderate-to-severe migraine attacks, including migraine pain and migraine-associated symptoms, compared to placebo.In addition, the overall rates of adverse events in this trial were similar for telcagepant and placebo.The new data were presented in London, England at the European Headache/Migraine Trust International Congress.
"These data build on the clinical program for telcagepant as a potential treatment for acute migraines," said Tony W. Ho, senior director, Clinical Research, Merck Research Laboratories. "We look forward to presenting additional data in the future."
More than 1200 patients treated for migraine attack in this trial
The reported findings are from a worldwide, multicenter, randomized, placebo-controlled clinical trial in adult patients with acute migraine.A total of 1,703 patients were randomized into the study and 1,294 administered study treatment.The 1,294 patients who experienced one moderate-to-severe migraine attack, as defined by the International Headache Society International Classification of Headache Disorders II, were treated with telcagepant at doses of either 300 mg (n=371), 150 mg (n=381), 50 mg (n=177) or placebo (n=365).
Overall treatment effect was assessed by analyzing five primary endpoints at two hours post-dose: pain freedom (reduction to no pain), pain relief (reduction to mild or no pain), absence of photophobia (sensitivity to light), absence of phonophobia (sensitivity to sound), and absence of nausea.Telcagepant (300 mg) met all five primary endpoints in the study.Secondary endpoints were: two to 24 hours sustained pain freedom (pain-free from two to 24 hours post-dose without recurrence, use of an optional second dose or rescue medication), total migraine freedom from two to 24 hours post-dose, and total migraine freedom at two hours post-dose.
Telcagepant relieved migraine pain and migraine associated symptoms in study
The treatment effect of the 300 mg and 150 mg doses of telcagepant was significantly greater than placebo for all five primary endpoints in the study (p<0.001 for both doses on all endpoints with the exception of p<0.050 for 150 mg dose on phonophobia):
- Two-hour pain relief: 55.6 percent and 53.9 percent of patients who received telcagepant 300 mg and 150 mg respectively reported their pain had been reduced at two hours compared to 32.9 percent for placebo;
- Two-hour pain freedom: 23.8 percent and 23.2 percent of patients who received telcagepant 300 mg and 150 mg respectively reported being pain-free at two hours compared to 10.7 percent for placebo;
- Absence of phonophobia: 55.8 percent and 50.5 percent of patients who received telcagepant 300 mg and 150 mg respectively reported they did not experience sensitivity to noise at two hours compared to 41.6 percent for placebo;
- Absence of photophobia: 48.5 percent and 46.3 percent of patients who received telcagepant 300 mg and 150 mg respectively reported they did not experience sensitivity to light at two hours compared to 32.6 percent for placebo; and
- Absence of nausea: 69.9 percent and 68.6 percent of patients who received telcagepant 300 mg and 150 mg respectively reported they did not experience nausea at two hours compared to 53.7 percent for placebo.
The 50 mg dose of telcagepant was included in this trial to further explore efficacy on the primary endpoints at the lower end of the dose range; it is not as effective as 150 mg and 300 mg dose and no statistical analysis was applied.
For the sustained pain freedom from two to 24 hours post-dose endpoint, the response rate was greater in patients who received telcagepant 300 mg compared to those receiving placebo (17.3 percent versus 7.2 percent, respectively; p<0.001).A similar pattern was observed for the measures of total migraine freedom at two hours and total migraine freedom at two to 24 hours post-dose. Responses to sustained pain freedom at two to 48 hours, an exploratory endpoint, also were reported and showed that more patients who received telcagepant reported being free of migraine pain up to 48 hours compared to those receiving placebo (p<0.001, not adjusted for multiplicity).
Telcagepant adverse event rates
In this trial, rates of overall adverse events observed (within 14 days post-dose) in patients treated with telcagepant 300 mg (36.2 percent) or 150 mg (32.0 percent) were similar to placebo (32.2 percent).The most common side effects reported in patients treated with telcagepant were fatigue (6.8 percent/300 mg and 3.9 percent/150 mg vs. 3.8 percent/placebo), dizziness (5.4 percent/300 mg and 2.4 percent for 150 mg vs. 3.3 percent/placebo), dry mouth (5.1 percent/300 mg and 4.5 percent for 150 mg vs. 5.2 percent/placebo), nausea (5.1 percent/300 mg and 3.4 percent/150 mg vs. 5.5 percent/placebo), upper abdominal pain (3.2 percent/300 mg and 1.0 percent/150 mg vs.1.6 percent/placebo) and somnolence (2.7 percent/300 mg and 3.7 percent/150 mg vs. 3.0 percent/placebo).There were no reports of serious drug-related adverse events in the study.
Merck continues to anticipate filing a New Drug Application (NDA) for telcagepant with the U.S. Food and Drug Administration in 2009.
Telcagepant is a CGRP receptor antagonist, potentially a new mechanism to treat acute migraine attacks
Telcagepant is a novel, oral CGRP receptor antagonist without direct vasoconstriction in development for treatment of acute migraine.It is an antagonist of the receptor for CGRP, a potent neuropeptide thought to play a central role in the underlying pathophysiology of migraine.CGRP and its receptors are found in many areas of the brain that are important for the transmission of migraine pain. During migraine attacks, CGRP binds to and activates CGRP receptors, which help transmit pain impulses.Telcagepant blocks CGRP from binding to its receptors within the nervous system and thereby is believed to inhibit the transmission of the pain signals that lead to migraine headaches.
About migraine
Migraine is a disabling disorder of the brain that affects 35 million Americans.Unlike a bad headache, migraines are characterized by attacks of intense, usually one-sided, throbbing head pain that can last from four to 72 hours.The pain associated with migraine is frequently accompanied by other symptoms, including nausea, vomiting and increased sensitivity to light and sound.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first.Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs.The Company devotes extensive efforts to increase access to medicines throughout far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them.Merck also publishes unbiased health information as a not-for-profit service.For more information, visit www.merck.com.
Forward-Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995.These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements.The forward-looking statements may include statements regarding product development, product potential or financial performance.No forward-looking statement can be guaranteed, and actual results may differ materially from those projected.Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2007 and in any risk factors or cautionary statements in the Company's periodic reports on form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.
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