Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine

Cephalalgia ◽  
2011 ◽  
Vol 31 (6) ◽  
pp. 712-722 ◽  
Author(s):  
David J Hewitt ◽  
Sheena K Aurora ◽  
David W Dodick ◽  
Peter J Goadsby ◽  
Yang (Joy) Ge ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Interim Analysis ◽  
Acute Treatment ◽  
Adaptive Design ◽  
Controlled Trial ◽  
Optimal Dose ◽  
Design Decision ◽  
Cgrp Receptor ◽  
Double Blind ◽  
Cgrp Receptor Antagonist

Background: This study evaluated the CGRP receptor antagonist MK-3207 for acute treatment of migraine. Methods: Multicenter, double-blind, randomized, placebo-controlled, parallel-group, two-stage adaptive study with two interim efficacy analyses to facilitate optimal dose selection. Migraine patients were initially randomized to MK-3207 2.5, 5, 10, 20, 50 and 100 mg or placebo to treat a moderate/severe migraine. One or more doses were to be discontinued based on the first interim analysis and a lower or higher dose could be added based on the second interim analysis. The primary endpoint was two-hour pain freedom. Results: A total of 547 patients took study medication. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5 mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100 mg) were continued into the second stage. After the second interim efficacy analysis, a 200 mg dose was added due to insufficient efficacy at the top three (20, 50, 100 mg) doses. A positive dose-response trend was demonstrated when data were combined across all MK-3207 doses for two-hour pain freedom ( p < .001). The pairwise difference versus placebo for two-hour pain freedom was significant for 200 mg ( p < .001) and nominally significant for 100 mg and 10 mg ( p < .05). The incidence of adverse events appeared comparable between active treatment groups and placebo, and did not appear to increase with increasing dose. Conclusions: MK-3207 was effective and generally well tolerated in the acute treatment of migraine.

Randomized controlled trial of the CGRP receptor antagonist telcagepant for prevention of headache in women with perimenstrual migraine

Cephalalgia ◽  
2015 ◽  
Vol 36 (2) ◽  
pp. 148-161 ◽  
Author(s):  
Tony W Ho ◽  
Andrew P Ho ◽  
Yang (Joy) Ge ◽  
Christopher Assaid ◽  
Regina Gottwald ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Receptor Antagonist ◽  
Alanine Aminotransferase ◽  
Controlled Trial ◽  
Cgrp Receptor ◽  
Double Blind ◽  
Treatment Difference ◽  
Clinical Adverse Event ◽  
Cgrp Receptor Antagonist

Aim 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 ≥3× 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.

Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention

Neurology ◽  
2014 ◽  
Vol 83 (11) ◽  
pp. 958-966 ◽  
Author(s):  
T. W. Ho ◽  
K. M. Connor ◽  
Y. Zhang ◽  
E. Pearlman ◽  
J. Koppenhaver ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Receptor Antagonist ◽  
Controlled Trial ◽  
Migraine Prevention ◽  
Cgrp Receptor ◽  
Randomized Controlled ◽  
Cgrp Receptor Antagonist

Examining the binding properties of MK-0974: A CGRP receptor antagonist for the acute treatment of migraine

2009 ◽  
Vol 602 (2-3) ◽  
pp. 250-254 ◽  
Author(s):  
Eric L. Moore ◽  
Christopher S. Burgey ◽  
Daniel V. Paone ◽  
Anthony W. Shaw ◽  
Yui S. Tang ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Acute Treatment ◽  
Cgrp Receptor ◽  
Binding Properties ◽  
Cgrp Receptor Antagonist

scholarly journals Potential for treatment benefit of small molecule CGRP receptor antagonist plus monoclonal antibody in migraine therapy

Neurology ◽  
2020 ◽  
Vol 94 (20) ◽  
pp. e2121-e2125 ◽  
Author(s):  
Kathleen Mullin ◽  
David Kudrow ◽  
Robert Croop ◽  
Meghan Lovegren ◽  
Charles M. Conway ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Small Molecule ◽  
Acute Treatment ◽  
Case Reports ◽  
Preventive Treatment ◽  
Clinical Report ◽  
Cgrp Receptor ◽  
Treatment Benefit ◽  
Receptor Antibody ◽  
Cgrp Receptor Antagonist

ObjectiveTo provide the first clinical report that 2 calcitonin gene-related peptide (CGRP) therapies, a small molecule CGRP receptor antagonist and an anti-CGRP receptor antibody, can be used concomitantly to treat refractory migraine.MethodsCase reports are presented of 2 patients participating in a long-term safety study of rimegepant 75 mg oral tablets for acute treatment (NCT03266588). After Food and Drug Administration approval of erenumab, both patients started subcutaneous erenumab monthly as allowed per protocol.ResultsPatients were women 44 and 36 years of age with ≥2 decades of self-reported suboptimal response to multiple migraine medications. Patient 1 used rimegepant for 6 months and then started erenumab 70 mg subcutaneous monthly. Despite a response to preventive treatment with erenumab, she experienced substantial relief treating 7 of 7 acute attacks with rimegepant and eliminated regular, frequent use of ibuprofen and a caffeinated analgesic. Patient 2 used rimegepant for 60 days before starting erenumab 140 mg subcutaneously monthly. While on erenumab, 9 of 9 attacks treated with rimegepant responded. She stopped near-daily use of injectable ketorolac and diphenhydramine. While using rimegepant alone or together with erenumab, patients reported no related adverse events.ConclusionsRimegepant 75 mg may be effective for acute treatment during concomitant erenumab preventive administration. The mechanism underlying the benefits of concomitant use of a small molecule CGRP receptor antagonist and an anti-CGRP receptor antibody is unknown and requires further study.ClinicalTrials.gov identifierNCT03266588.Classification of evidenceThis study provides Class IV evidence that for patients with migraine using erenumab, rimegepant is effective for acute treatment.

Sustained pain freedom and no adverse events as an endpoint in clinical trials of acute migraine treatments: Application to patient-level data from a trial of the CGRP receptor antagonist, telcagepant, and zolmitriptan

Cephalalgia ◽  
2010 ◽  
Vol 31 (3) ◽  
pp. 296-300 ◽  
Author(s):  
David W Dodick ◽  
James Kost ◽  
Christopher Assaid ◽  
Christopher Lines ◽  
Tony W Ho
Keyword(s):  
Pain Relief ◽  
Adverse Events ◽  
Receptor Antagonist ◽  
Controlled Trial ◽  
Composite Endpoint ◽  
Cgrp Receptor ◽  
Patient Level Data ◽  
Patient Level ◽  
Level Data ◽  
Cgrp Receptor Antagonist

Background: 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. Methods: 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). Results: 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. Conclusion: Composite efficacy-plus-tolerability endpoints may be useful for facilitating comparisons between treatments.

scholarly journals A Short on Ubrogepant

2021 ◽  
pp. 79-81
Author(s):  
S. Padmaja ◽  
J. Mohan
Keyword(s):  
Receptor Antagonist ◽  
Research Process ◽  
Calcitonin Gene Related Peptide ◽  
Review Article ◽  
Acute Migraine ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Acute Attacks ◽  
Cgrp Receptor Antagonist

Migraine is a mysterious disorder characterized by pulsating head ache, which is actually characterized to one side and comes in attacks which will be lasting for about 3-48 hours and can be associated with nausea,vomiting,sensitivity to sound,flashes of light,vertigoand diarrhoea [1]. Most of the drugs which are in current use for actue migraine like triptans, treats the disorder symptomatically. A novel group of drugs has been in research for the migraine which treats the disorder pathologically. Calcitonin gene – related peptide (CGRP) has a major role in the pathophysiology of the disorder and hence CGRP receptor antagonist, known as Gepants are in the research process [2]. Gepants are being studied for the efficacy of treating acute migraine [2]. This article will be a review article about the drug – Ubrogepant, which is approved for treatment of migraine with acute attacks in adults [3].

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