telcagepant and Pain

Endpoints used to evaluate the efficacy of acute anti-migraine drugs do not measure the tolerability. Sustained pain-free response with no adverse events has been recommended as a composite endpoint which measures the efficacy and tolerability attributes that patients desire.. The aim of this study was to evaluate new composite efficacy-plus-tolerability endpoints based on a post-hoc analysis of patient-level data from a previous randomized, placebo-controlled trial of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, and zolmitriptan in the acute treatment of migraine. Endpoints were 2-24-hour sustained pain freedom and no adverse events from 0-24 hours (SPF24NAE), 2-24 hour sustained pain relief and no adverse events from 0-24 hours (SPR24NAE), pain freedom at 2 hours and no adverse events from 0-24 hours (PF2NAE), and pain relief at 2 hours and no adverse events from 0-24 hours (PR2NAE).. Compared with placebo, both telcagepant 300 mg and 150 mg achieved nominal superiority (p values <.05) for SPF24NAE, SPR24NAE, PF2NAE and PR2NAE. Zolmitriptan 5 mg showed nominal superiority versus placebo for SPF24NAE, SPR24NAE and PF2NAE, but not PR2NAE. Telcagepant 300 mg showed nominal superiority versus zolmitriptan for SPF24NAE, SPR24NA and PR2NAE.. Composite efficacy-plus-tolerability endpoints may be useful for facilitating comparisons between treatments.

Topics: Adult; Analgesics; Azepines; Calcitonin Gene-Related Peptide Receptor Antagonists; Double-Blind Method; Female; Humans; Imidazoles; Male; Migraine Disorders; Oxazolidinones; Pain; Research Design; Serotonin 5-HT1 Receptor Antagonists; Tryptamines

To evaluate whether the same or different patients respond to triptans and telcagepant.. Telcagepant is an oral calcitonin gene-related peptide receptor antagonist with acute antimigraine efficacy comparable to oral triptans. It is currently unknown whether migraine patients who cannot be adequately helped with triptans might benefit from treatment with telcagepant.. Post-hoc analysis of data from a randomized, controlled trial of telcagepant (150 mg, 300 mg) zolmitriptan 5 mg, or placebo for a moderate/severe migraine. Responder rates were analyzed according to patients' self-reported historical triptan response (HTR): (1) good HTR (N = 660): response in 75-100% of attacks; (2) intermediate HTR (N = 248): response in 25-74% of attacks; (3) poor HTR/no use (N = 407): response in < 25% of attacks, or patient did not take triptans. A limitation of the analysis is that the last subgroup comprised mainly (91%) patients who reported that they did not take triptans, but it was not known whether these patients were triptan-naïve or had previously used triptans and stopped taking them.. For zolmitriptan, 2-hour pain relief rates were higher in the good HTR subgroup (116/162, 72%) than in the intermediate (29/62, 47%) and poor/no use (44/111, 40%) HTR subgroups. The 2-hour pain relief rates were similar across HTR subgroups for telcagepant 150 mg (48-58%), 300 mg (52-58%), and placebo (26-31%). In the poor/no use HTR subgroup, more patients receiving telcagepant 300 mg (56/98, 57.1%) had 2-hour pain relief than those receiving zolmitriptan (44/111, 39.6%; odds ratio = 2.11 [95% CI: 1.20,3.71], P = .009); the percentage for telcagepant 150 mg (57/119, 47.9%) was not significantly different from zolmitriptan (odds ratio = 1.41 [95% CI: 0.82, 2.40], P = .211).. This suggests that different patients may respond to triptans or telcagepant 300 mg. Caution should be exercised in interpreting the results because of the post-hoc nature of the analysis (clinical trial registry: NCT00442936).

Topics: Adult; Azepines; Calcitonin Gene-Related Peptide Receptor Antagonists; Double-Blind Method; Female; Humans; Imidazoles; Male; Migraine Disorders; Oxazolidinones; Pain; Surveys and Questionnaires; Tryptamines

Topics: Azepines; Clinical Trials as Topic; Humans; Imidazoles; Migraine Disorders; Pain; Treatment Outcome