Clinical trial NCT03076970: Effect of Single Oral Doses of Lasmiditan When Coadministered With Single Oral Doses of Sumatriptan in Healthy Participants
Official title: A Randomized, Double-Blind, Three Period, Cross-Over Study to Evaluate the Effect of Single Oral Doses of Lasmiditan When Coadministered With Single Oral Doses of Sumatriptan (Imitrex) in Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Migraine
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: SNBL Clinical Pharmacology Center, Inc.
name: CoLucid Pharmaceuticals
First posted: 2017-03-10
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This is a randomized, double-blind, three-period, cross-over study to investigate the effect of sumatriptan (Imitrex) 100 mg on the pharmacodynamics and pharmacokinetics of lasmiditan 200 mg.

Detailed description: This is a randomized, double-blind, three-period, cross-over study to investigate the effect of single doses of sumatriptan (Imitrex) 100 mg on the pharmacodynamics of single doses of lasmiditan 200 mg. The study will last approximately 6 weeks including up to 3 weeks for screening and 22 days on study. Screening will be conducted within approximately 21 days of the first dose of study medication. Each dosing period will last 3 days (Day 1, Day 1, and Day 2). A wash-out period of 6 days will take place between each dose. The End of Study Visit (EoS) will take place 5 (+/- 2) days after the third dosing period is completed.

Eligibility criteria: Inclusion Criteria:

* Male or female aged 18-60 years, inclusive.
* Able and willing to give written informed consent.
* Body mass index (BMI) between 18 and 32 kilograms per square meter (kg/m²), inclusive.
* Participants must be able to refrain from consuming xanthine, quinine and caffeine containing beverages, and must refrain from prolonged intensive physical exercise during the study (from 72 hours prior to dosing until the end of study).
* Women must be:

  * not pregnant
  * not breast-feeding
  * not planning to become pregnant during the study
* All females must have a negative serum pregnancy test at screening and a negative urine pregnancy test at check-in on Day -1 of each period. All women must agree to use an adequate method of contraception during the study and for 30 days following the end-of-study.
* Male participants must agree to utilize a highly effective method of contraception (condom plus spermicide) during heterosexual intercourse from clinic admission until 30 days following the end of study.
* Male participants must agree to refrain from sperm donation from clinic admission until at least 30 days following the end of study.
* Participants must be able to swallow multiple pills simultaneously.
* Participants must be able to understand the requirements of the study and must be willing to comply with the requirements of the study.

Exclusion Criteria:

* Any medical condition, clinical laboratory test or other reason which in the judgment of the Investigator or designee makes the participant unsuitable for the study.
* Any clinically significant abnormalities (as determined by the Principal Investigator or designee) in hematology, blood chemistry and/or urinalysis lab tests at screening or at Period 1 D-1.
* Known hypersensitivity to lasmiditan, sumatriptan (Imitrex), or to any excipient of lasmiditan or sumatriptan (Imitrex) oral tablets.
* Use of any prescription medication, including monoamine oxidase A (MAO-A) inhibitors and other drugs associated with serotonin syndrome, within 14 days prior to dosing (except hormonal contraceptives) except for 5-HT1 (serotonin) agonists and selective serotonin reuptake inhibitors.
* History, symptoms, or signs of ischemic cardiac, cerebrovascular, or peripheral vascular syndromes including but not limited to angina pectoris, myocardial infarction, silent myocardial ischemia (Ischemic cardiac syndromes), stroke, transient ischemic attacks (cerebrovascular syndromes), and ischemic bowel disease (peripheral vascular disease).
* History, symptoms, or signs of vasospastic coronary artery disease.
* History, symptoms, or signs of arrhythmia or Wolff Parkinson White (WPW) syndrome that could affect the participant's safety in the opinion of the Investigator or designee.
* History, symptoms, or signs of severe hepatic impairment.
* History, symptoms, or signs of diabetes.
* History within the previous 3 years or current evidence of abuse (according to Diagnostic and Statistical Manual of Mental Disorders, 4th. Edition \[DSM-IV\] criteria) of any drug, prescription or illicit, or alcohol; a positive urine screen for drugs of abuse or breathalyzer alcohol test.
* Positive urinary test for drugs of abuse and/or alcohol breath test at Screening and/or at check-in on Day -1 of each Period. Cotinine will be included at screening only.
* History of orthostatic hypotension with or without syncope.
* Supine systolic blood pressure (BP) \> 135 millimeters of mercury (mmHg), diastolic BP \> 85 mm Hg, respiratory rate \>20 breaths per minute, pulse \>90 beats per minute, or temperature \>37.5º at Screening. Low values on any vital sign measurement will be assessed at the discretion of the Investigator or designee. For orthostatic vital signs, any decrease in systolic and/or diastolic blood pressure great than 20 mmHg. Any other changes will be assessed at the discretion of the Investigator or designee.
* Electrocardiogram (ECG) changes including QT interval prolongation and congenital long QT syndrome.
* Electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, or other medicinal products that lead to QT prolongation.
* Any clinically significant alanine aminotransferase (ALT), alkaline phosphatase (AP), aspartate aminotransferase (AST), or bilirubin abnormalities judged by the Investigator or designee at Screening.
* Treatment with centrally active drugs or those affecting peripheral cholinergic transmission within 3 months of study entry.
* Consumption of grapefruit, grapefruit juice, Seville oranges, Seville orange juice, or beverages containing any of these juices or consumption of members of the mustard green family (including kale, broccoli, watercress, collard greens, kohlrabi, Brussels sprouts, and mustard (i.e. seeds, greens, spice or the condiment)) within 72 hours of dosing.
* Tobacco or nicotine users except participants who stopped using tobacco or nicotine 1 year or more before signing the informed consent.
* Participant is at imminent risk of suicide or had a suicide attempt within 6 months prior to screening .
* Participation in any clinical trial of an experimental drug or device in the previous 30 days.
* Positive Hepatitis C antibody, Hepatitis B surface antigen, or positive human immunodeficiency virus (HIV) antibody.
* Participants who donated plasma in the 7 days or blood in the 3 months - Participants with an inability to communicate well with the Investigator or designee and study staff (i.e., language problem, poor mental development or impaired cerebral function).
* Inability to fast or consume the food provided in the study.
* Relatives of or staff directly reporting to the Investigator.

Primary outcomes:
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Systolic Blood Pressure
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Diastolic Blood Pressure
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Pulse Rate
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Temperature
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in Vital Signs: Respiratory Rate
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Heart Rate
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) PR Duration
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QRS Duration
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcB - Bazett's Correction Formula
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: QTcF - Fridericia's Correction Formula
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) QT Duration
timeFrame: Pre-dose, 24 hours post-dose
measure: Pharmacodynamics- Change From Pre-dose to 24 Hours in ECGs: Summary (Mean) RR Duration
timeFrame: Pre-dose, 24 hours post-dose
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: Pharmacokinetics - Cmax
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours following the dose at time 0 in each dosing period
measure: Pharmacokinetics - AUC0-t
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours following the dose at time 0 in each dosing period
measure: Pharmacokinetics - Tmax
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24 and 30 hours following the dose at time 0 in each dosing period
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: SNBL Clinical Pharmacology Unit
state: Maryland
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: