So, und hier mal aktuelle Studienergebnisse zu Telcagepant, die ich im Netz gefunden habe. Leider auf Englisch und sehr lang. Aber wen es interessiert, der kann sich ja mal durchackern. Knappes Fazit: Wann es
zur Zulassung kommt, ist weiter offen, aber die Untersuchungsergebnisse sind positiv und wir dürfen weiter hoffen!
“July 02, 2010 – Elsevier Global Medical News
By Sherry Boschert
LOS ANGELES (EGMN) – The experimental drug telcagepant for acute migraine therapy appears to be tolerated by patients with stable coronary artery diseaseand consistently effective in various subgroups of patients, several analyses of randomized, double-blind, placebo- or active-controlled studies show.
The results, presented in fiveposters at the annual meeting of the American Headache Society, suggest that acute treatment with the drug is safe in migraineurs with stable cardiovascular disease and effective in patients with or without aura, with migraines that are or are not associated with menstruation, or who have a history of opioid treatment.
A separate study found that telcagepant appeared to be unappealing to recreational polydrug users and thus to have no abuse potential. In another analysis, the addition of ibuprofen or acetaminophen to telcagepant therapy produced a statistically insignificant improvement in efficacy.
The studies were led by employees of Merck, which is developing telcagepant and which funded the studies.
Previous studies have shown that telcagepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist, is effective in acute treatment of migraine (Neurology 2009;73:970-7; Lancet 2008;372:2115-23; Neurology 2008;70:1304-12).
Merck also had been developing the drug for migraine prophylaxis, but stopped those trials when some patients taking twice-daily doses for 3 months developed elevated liver enzyme levels, a company spokeswoman said in an e-mail interview after the meeting. Following discussions with the U.S. Food and Drug Administration at the end of 2009, Merck is conducting an additional safety study this year before regulators consider the drug further –a 6-month study of 4,500 females with menstrually associated migraine who will take 140 mg of telcagepant or placebo once daily for 7 consecutive days on a monthly basis.
In a double-blind, crossover study, patients with migraines and stable coronary artery disease (CAD) were randomized to one of two treatment groups. Patients in the first group treated up to 12 moderate to severe migraines with telcagepant in a 280-mg tablet plus a 300-mg capsule during a 6-week period, then treated 12 more migraines in the next 6-week period with acetaminophen 1,000 mg. Patients in the second group got placebo for the first moderate to severe migraine attack, then acetaminophen for up to 11 more migraines in the first 6-week period; in the second 6 weeks, up to 12 migraines were treated with the telcagepant regimen.
Final data were available to analyze safety in 184 patients and efficacy in 105 patients.
Adverse events were reported within 48 hours of treatment by 17 of 98 patients on telcagepant (17%) and 9 of 86 patients on acetaminophen (10%), reported Dr. Tony Ho, senior director of clinical research at Merck Research Laboratories, North Wales, Pennsylvania, and his associates. Drug-related adverse events were reported by eight patients (8%) on telcagepant and four (5%) on acetaminophen. No patients stopped treatment because of adverse events.
Three serious vascular events –two reports of chest pain after telcagepant and one report of renal artery stenosis after acetaminophen –were sent for adjudication by a blinded independent expert committee. The committee declared all to be non-thromboembolic events, and each occurred longer than 48 hours after migraine treatment. No patients had transaminase elevations three times the upper limit of normal or higher.
The study did not find significant differences in efficacy, perhaps because of the small number of patients, the investigators suggested. No pain was reported in 13 (25%) of 52 patients 2 hours after taking telcagepant, compared with 10 (19%) of 53 patients on placebo.
When asked about those findings, Dr. Leslie Kelman, medical director of the Headache Center of Atlanta, said in an interview that it appears that the investigators showed in one of the studies that “there isn’t any significant risk from using telcagepant in patients” with CAD. “That’s a huge plus,” said Dr. Kelman, pointing out that clinicians do not prescribe triptans for patients who have had CAD because of the risks. “This could be an alternative for patients who can’t use triptans.”
A pooled analysis of single-attack data from three randomized, double-blind, placebo-controlled studies involving a total of 3,829 patients compared the efficacy of 140 mg or 150 mg of telcagepant, 280 mg or 300 mg of the drug, or placebo.
For migraine with aura, 21% of 230 patients on the lower doses of telcagepant and 28% of 222 patients on the higher doses were pain-free 2 hours after treatment, compared with 10% of 233 patients on placebo. For migraine without aura, 21% of 1,020 patients on lower-dose telcagepant, 24% of 1,019 patients on higher doses, and 10% of 996 patients on placebo were pain-free after 2 hours. Rates were higher for pain relief at 2 hours but similar between aura and no-aura subgroups.
For menstrually associated migraines, 52% of 216 patients on lower doses and 56% of 209 on higher doses were pain-free after 2 hours, compared with 29% of 221 patients on placebo. For non-menstrual migraines, 54% of 571 patients on lower doses, 60% of 557 on higher doses, and 33% of 557 on placebo were pain-free at 2 hours, Dr. Ho and his associates reported.
Among patients who reported that previous migraine treatment with a triptan was of “no use,” 62% of 343 patients on the lower doses of telcagepant and 56% of 339 on the higher doses were pain-free after 2 hours, compared with 39% of 346 patients on placebo.
Among patients who reported that previous treatment with a non-steroidal anti-inflammatory drug was of “no use,” 53% of 443 patients on lower-dose telcagepant, 57% of 418 on higher doses, and 26% of 484 patients on placebo were free of pain after 2 hours.
The investigators in this study “analyzed the sort of things we want to know,” said Dr. Kelman, who was not involved in the telcagepant studies but has been a speaker of Merck – the developer of telcagepant. “What sort of results do you get using telcagepant? But even more so, what are the results if you break down the data by certain groups – patients with aura, without aura, patients who have menstrual migraine versus those who don’t have menstrual migraine, or patients who have used a triptan before?
“The conclusion was that basically, no matter which group you look at, the results are very similar.”
A post-hoc analysis of data from a randomized, double-blind placebo-controlled trial suggests that patients with or without a prior response to opioid treatment for migraines might respond similarly to telcagepant. Among 111 patients who reported at least a 75% response to prior opioid therapy, 64% of those who took telcagepant 140 mg for a migraine attack and 69% on 280 mg were pain-free after 2 hours, compared with 54% on placebo.
Among 243 patients who reported less than a 75% response to prior opioid therapy, telcagepant brought pain relief at 2 hours in 54% of patients who received 140 mg and in 55% of patients on 280 mg, compared with 26% of patients on placebo. Among 1,163 patients with no history of opioid use for migraine, freedom from pain at 2 hours was reported by 60% on 140 mg telcagepant, 56% on 280 mg telcagepant, and 32% on placebo, Dr. Ho and his associates reported.
The findings require confirmation in prospective studies with larger numbers of patients, they suggested.
Thirty-six healthy recreational polydrug users were randomized in a double-blind, six-period crossover study to evaluate their liking for single doses of placebo or telcagepant 280 mg, 560 mg, 1,120 mg, or 1.5 mg or 3 mg of alprazolam as a positive control known to have abuse potential. Patient ratings on a Drug Liking visual analogue scale showed no significant differences between telcagepant and placebo, while alprazolam was ranked significantly higher than telcagepant or placebo, reported Rebecca Blanchard, Ph.D., also of Merck Research Laboratories, and her associates.
Combining telcagepant with ibuprofen or acetaminophen did not significantly change efficacy in a pilot randomized, double-blind, placebo-controlled study, reported Dr. David J. Hewitt of Merck Research Laboratories and his associates.
Pain freedom at 2 hours was reported by 35% of 145 patients who took telcagepant 280 mg plus ibuprofen 400 mg, 38% of 133 patients who took the same telcagepant dose plus acetaminophen 1,000 mg, 31% who got telcagepant alone, and 11% who received placebo.
Previous studies have suggested that adding naproxen or acetaminophen to sumatriptan or rizatriptan, respectively, significantly improved efficacy compared with triptan monotherapy, they noted.”
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