Multiple, Once-daily, Oral Doses of 170 Mg Atogepant for 28 Days Are Safe and Well Tolerated with No Clinically Significant Effect on Alanine Aminotransferase in Healthy Adults

K. Chris Min, MD, PhD

AHSAM 2020 - Oral session
Published on September 3, 2020

2 minute listen

7 minute read

Key messages

  • Once-daily oral atogepant 170 mg for the prevention of migraine was safe and generally well-tolerated over a 28-day period.
  • Atogepant is rapidly absorbed and has an estimated half-life of ~10 hours.
  • The potential risk of liver injury from multiple doses of atogepant appears to be relatively low.
  • Background

    What do we already know about this topic?
  • Findings

    What does this study add?
  • Perspectives

    How does this study impact clinical practice?
  • Expert commentary

    by Jessica Ailani, MD, FAHS, FAAN

Key messages

  • Once-daily oral atogepant 170 mg for the prevention of migraine was safe and generally well-tolerated over a 28-day period.
  • Atogepant is rapidly absorbed and has an estimated half-life of ~10 hours.
  • The potential risk of liver injury from multiple doses of atogepant appears to be relatively low.

Background

What do we already know about this topic?

  • Calcitonin gene–related peptide (CGRP) is a known trigger of migraine attacks.1,2
  • Despite demonstrating efficacy in migraine treatment, the development of two early CGRP receptor antagonists was halted due to elevated alanine aminotransferase (ALT) in clinical trials.3,4
  • Atogepant is a novel oral CGRP receptor antagonist in development for the prevention of migraine.
  • In a 12-week Phase 2/3 randomized, placebo-controlled, clinical trial atogepant demonstrated efficacy and was well-tolerated at doses of 10 mg QD to 60 mg BID.1

How was this study conducted?

  • A single-center, randomized, double-blind, placebo-controlled study of 34 participants aged 18 to 55 years randomized 2:1 to oral atogepant 170 mg or placebo once daily for 28 days.
  • Outcome measures included change in plasma concentration and elimination half-life of atogepant, type and frequency of adverse events, and change from baseline in ALT.

Findings

What does this study add?

  • Atogepant 170 mg was rapidly absorbed following oral administration; median time to maximum concentration was ~2 hours and mean elimination half-life was ~10 hours.
  • Atogepant 170 mg was generally well tolerated with all reported adverse events (AE) being mild, except for one serious AE, a subarachnoid hemorrhage, unrelated to the study drug (bicycle accident).
  • The most frequent AEs reported (≥13% of participants) were fatigue, headache, decreased appetite, dizziness, nausea, back pain, vessel puncture-site pain, erythema, and pruritus.
  • Fatigue was the most common at 48%.
  • Two participants discontinued treatment with atogepant due to AEs.  
  • At the end of the study period, mean fold change in ALT from baseline was similar in both treatment groups (0.79 [95% CI, 0.70-0.89] with atogepant versus 0.99 [95% CI, 0.84-1.17] with placebo).
  • There were no ALT elevations three or more times the upper limit of normal at any post-dose time point.

Perspectives

How does this study impact clinical practice?

  • Atogepant 170 mg provides a well-tolerated preventative treatment option for patients with migraine and adds to the growing number of CGRP therapies available.
  • The potential risk of liver injury from multiple doses of atogepant appears to be relatively low.
  • The convenience of an oral therapy could aid treatment compliance while alleviating some of the burden associated with intravenous or subcutaneous administration.

Perspectives

How does this study impact clinical practice?

  • Atogepant 170 mg provides a well-tolerated preventative treatment option for patients with migraine and adds to the growing number of CGRP therapies available.
  • The potential risk of liver injury from multiple doses of atogepant appears to be relatively low.
  • The convenience of an oral therapy could aid treatment compliance while alleviating some of the burden associated with intravenous or subcutaneous administration.

This is a highlights summary of an oral session given at the AHSAM 2020 Virtual Annual Scientific Meeting and presented by:

K. Chris Min, MD, PhD
Formerly of Merck & Co., Inc.
Kenilworth, New Jersey

The content is produced by Infomedica, the official reporting partner of ASHAM 2020 Virtual Annual Scientific Meeting. The summary text was drafted by Goldcrest Medical Writing, reviewed by Marco Vercellino, MD, an independent external expert, and approved by Jessica Ailani, MD, FAHS and Mark J. Burish, MD, PhD, the scientific editors of the program.

The presenting authors of the original session had no part in the creation of this conference highlights summary.

In addition, an expert commentary on the topic has been provided by:

Jessica Ailani, MD, FAHS, FAAN
Director, Medstar Georgetown Headache Center
Vice Co-Chair Strategic Planning Medstar Neurology
Professor of Clinical Neurology
Medstar Georgetown University Hospital, Washington D.C. USA

Jessica Ailani, MD
Director Medstar Georgetown Headache Center, Associate Professor Neurology
Department of Neurology, Georgetown University Hospital
Washington D.C., District of Columbia

Jessica Ailani is a Professor of Clinical Neurology, Director of the Georgetown Headache Center, and Vice Co-Chair of Strategic planning Neurology at MedStar Georgetown University Hospital in Washington, DC. Dr. Ailani is a fellow of the American headache society and the American Academy of Neurology. She holds a position on the board as a member at large, is the co-chair of the Practice management group and is on the scientific and Scottsdale program planning committees . She is section editor of Unusual Headache Syndromes for Current Pain and Headache Reports and a reviewer for several professional journals. Dr. Ailani has presented nationally on topics surrounding headache medicine. 

1. Goadsby PJ, Holland PR, Martins-Oliveira M, et al. Pathophysiology of Migraine: A Disorder of Sensory Processing. Physiol Rev 2017;97:553-622.

2. Goadsby PJ, Dodick DW, Trugman JM, et al. Orally Administered Atogepant Was Efficacious, Safe, and Tolerable for the Prevention of Migraine: Results From a Phase 2b/3 Study (S17.001). Neurology 2019; 92(15 Supplement): S17.001.

3. Ho TW, Connor KM, Zhang Y, et al. Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. Neurology 2014;83:958-966.

4. Ho TW, Ho AP, Ge YJ, et al. Randomized controlled trial of the CGRP receptor antagonist telcagepant for prevention of headache in women with perimenstrual migraine. Cephalalgia 2016;36:148-161.



Headache
Migraine


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