A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Erenumab on Exercise Time During a Treadmill Test in Patients With Stable Angina.

Abstract

OBJECTIVE:

To determine the potential impact of erenumab, a human anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, on total exercise time (TET), time to exercise-induced angina, and ST depression in a double-blind, placebo-controlled study in patients with stable angina due to documented coronary artery disease.

BACKGROUND:

The relative importance of the CGRP receptor pathway during myocardial ischemia has not been established.

METHODS:

An exercise treadmill test was conducted following a single IV infusion of erenumab 140 mg or placebo. The primary endpoint was the change from baseline in exercise duration as measured by TET with a noninferiority margin of -90 seconds. Safety follow-up visits occurred through week 12. Eighty-eight participants were included in the analysis.

RESULTS:

LS mean (SE) change in TET was -2.9 [14.8] seconds in the erenumab group and 8.1 [14.4] seconds in placebo; adjusted mean (90% CI) treatment difference was -11.0 (-44.9, 22.9) seconds. The CI lower bound (-44.9 sec) did not reach pre-defined non-inferiority margin of -90 seconds, demonstrating that TET change from baseline in the erenumab group was non-inferior to placebo. There was no difference in time to exercise-induced angina in erenumab and placebo groups (median [90% CI] time of 500 [420, 540] vs 508 [405, 572] seconds; hazard ratio [90% CI]: 1.11 [0.73, 1.69], P = .69) or time to onset of ≥1 mm ST-segment depression (median [90% CI] time of 407 [380, 443] vs 420 [409,480] seconds; hazard ratio [95% CI]: 1.14 [0.76, 1.69], P = .59). Adverse events were reported by 27% and 32% of patients in erenumab and placebo groups.

CONCLUSIONS:

Erenumab did not adversely affect exercise time in a high cardiovascular risk population of patients, supporting that inhibition of the canonical CGRP receptor does not worsen myocardial ischemia.

• Authors: Christophe Depre, Lubomir Antalik, Amaal Starling, Michael Koren, Osaro Eisele, Robert A Lenz, Daniel D Mikol
• Journal: Headache (Headache) Vol. 58 Issue 5 Pg. 715-723 (May 2018) ISSN: 1526-4610 [Electronic] United States
• PMID: 29878340 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2018 The Authors. Amgen Inc.

Chemical References

• Antibodies, Monoclonal, Humanized
• Calcitonin Gene-Related Peptide Receptor Antagonists
• erenumab

Topics

• Aged
• Angina, Stable (chemically induced, physiopathology)
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Calcitonin Gene-Related Peptide Receptor Antagonists (administration & dosage, adverse effects)
• Double-Blind Method
• Electrocardiography (drug effects)
• Exercise Test (drug effects)
• Female
• Humans
• Male
• Middle Aged
• Time Factors