Lasmiditan in Japanese Patients with Common Migraine Comorbidities or Concomitant Medications: A Post Hoc Safety and Efficacy Analysis from the MONONOFU Study

Abstract

Background

Migraine is often comorbid with other disorders. People with migraine may be prescribed one or more concomitant medications. This post hoc analysis assessed the safety and efficacy of lasmiditan in Japanese people with migraine comorbidities or using concomitant medications.

Patients and Methods

The MONONOFU study was a Phase 2, randomized, placebo-controlled, multicenter study of lasmiditan for acute migraine treatment in Japanese adults. Patients reported comorbidities (pre-existing or coexisting conditions) during screening. Concomitant medications (any drugs taken ±48 hours of the study drug) and treatment-emergent adverse events (TEAEs) were recorded in a paper diary. Study drug efficacy (pain freedom 2 hours after administration of study drug) was reported in an eDiary. Logistic regression models were used for subgroup analyses of safety (incidence of TEAEs) and efficacy (pain freedom at 2 hours post dose) of lasmiditan in relation to presence/absence of comorbidities, and safety in relation to concomitant medications.

Results

Common comorbidities (occurring in ≥10% of any lasmiditan dose group) were seasonal allergies, allergic rhinitis, tension-type headache, cervicobrachial syndrome, dysmenorrhea, nasopharyngitis, musculoskeletal stiffness, chronic gastritis, constipation, and insomnia. There was no significant interaction of treatment with comorbidity for safety or efficacy. There was also no significant interaction between treatment and concomitant medication groups of special interest (acetaminophen/nonsteroidal anti-inflammatory drugs, triptans, antiemetics, central nervous system depressant medications, serotonergic medications, antiepileptics, antihypertensive medications, Chinese herbal medicines, and contraceptives) for incidence of TEAEs.

Conclusion

In Japanese people with migraine, the safety of lasmiditan appeared to be independent of common comorbidities and concomitant medications; efficacy appeared to be independent of comorbid conditions.

Clinical Trials Registration

NCT03962738 (ClinicalTrials.gov).

Keywords:

• comorbidity
• drug therapy
• headache
• Japan
• migraine disorders
• safety

Abbreviations

ACE, acetaminophen; AE, adverse event; CI, confidence interval; CNS, central nervous system; LTN, lasmiditan; MedDRA, Medical Dictionary for Regulatory Activities; mITT, modified intent-to-treat; NSAID, nonsteroidal anti-inflammatory drug; OR, odds ratio; PT, Preferred Term; SOC, System Organ Class; TEAE, treatment-emergent adverse event.

Data Sharing Statement

Eli Lilly and Company provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the United States and the European Union and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.

Acknowledgments

The authors would like to thank all study participants. Medical writing assistance was provided by Koa Webster, PhD, and Prudence Stanford, PhD, CMPP, of ProScribe – Envision Pharma Group, and was funded by Eli Lilly Japan K.K. and Daiichi Sankyo Company, Limited. ProScribe’s services complied with international guidelines for Good Publication Practice.

Author Contributions

All authors made a significant contribution to the work reported, either in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas. All authors took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

SK reports lecture fees from Daiichi Sankyo Company, Limited and Otsuka Pharmaceutical Co., Ltd., outside the submitted work. NI reports payments or honoraria for lectures and presentations from Eli Lilly Japan K.K. and Daiichi Sankyo Company, Limited, during the conduct of the study; personal fees from Otsuka Pharmaceutical, Amgen, and Sawai Pharmaceutica, outside the submitted work. YT, AO, and MK are employees of Eli Lilly Japan K.K. and have minor shareholdings in Eli Lilly and Company. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was sponsored by Eli Lilly Japan K.K. (Kobe, Japan), manufacturer of lasmiditan. Eli Lilly Japan K.K. was involved in the study design, data collection, data analysis, and preparation of the manuscript.