Oral CGRP Receptor Antagonist Showed Statistically Significant Improvement In Migraine Relief Versus Placebo

Main Category: Headache / Migraine
Also Included In: Clinical Trials / Drug Trials
Article Date: 08 Sep 2008 - 8:00 PDT

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Merck Sharp & Dohme Limited 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 at the European Headache and Migraine Trust International Congress 2008 in London.1

"These data build on the clinical programme for telcagepant as a potential treatment for acute migraines," said Tony W. Ho, senior director, Clinical Research, Merck Research Laboratories, US. "We look forward to presenting additional data in the future."

More than 1,200 patients treated for migraine attack in this trial

The reported findings are from a worldwide, multicentre, randomised, placebo-controlled clinical trial in adult patients with acute migraine. A total of 1,703 patients were randomised 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 analysing 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 hour 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 sensitivity to light 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 150mg and 300mg 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, were also 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).

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/300mg 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/300mg 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 Sharp & Dohme Limited anticipates filing telcagepant for approval 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 the most common neurological condition in the developed world. It is more prevalent than diabetes, epilepsy and asthma combined - eight million people in the UK have migraine.2 Unlike a bad headache, migraines are characterised 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 Sharp & Dohme Limited

Merck Sharp & Dohme Limited (MSD) is the UK subsidiary of Merck & Co., Inc., of Whitehouse Station, New Jersey, USA, a leading research-based pharmaceutical company that discovers, develops, manufactures and markets a wide range of innovative pharmaceutical products to improve human health. Merck Sharp & Dohme Limited

Forward-Looking Statement

This press release contains "forward-looking statements" about product development, product potential or about financial performance based on current expectations of the management of Merck & Co., Inc. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck & Co., Inc. undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

References

1. Connor, et al. Efficacy and Safety of telcagepant (MK-0974), a Novel Oral CGRP Receptor Antagonist, for Acute Migraine Attacks. Poster, European Headache and Migraine Trust International Congress, London, England, September 2008.

2. The Migraine Trust . Website last accessed in August 2008.

Merck Sharp & Dohme Limited