A Study of Lasmiditan in Healthy Volunteers

An Open-Label, 2-Part Study to Investigate the Effect of Lasmiditan on the Pharmacokinetics of Dabigatran and Rosuvastatin in Healthy Volunteers

The main purpose of the study is to investigate the blood concentrations of dabigatran etexilate and rosuvastatin when taken alone compared to when taken together with lasmiditan in healthy participants. The safety and tolerability of dabigatran etexilate or rosuvastatin in combination with lasmiditan will also be evaluated in healthy participants. The study has two parts. Each part will last up to 17 days, not including screening.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lasmiditan; Drug: Dabigatran Etexilate; Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 138623
    • Lilly Centre for Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Are overtly healthy
• Body mass index (BMI) of 18.5 to 35 kilograms per meter squared (kg/m²)

Exclusion Criteria:

• have known allergies to lasmiditan, dabigatran, rosuvastatin-related compounds or any components of the formulation of lasmiditan, dabigatran, rosuvastatin, or a history of significant atopy
• have an abnormal blood pressure and/or pulse rate as determined by the investigator
• have clinically significant abnormalities on electrocardiogram (ECG) as determined by investigator
• have a history or presence of cardiovascular, respiratory, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study interventions; or of interfering with the interpretation of data. Appendectomy, splenectomy, and cholecystectomy are considered as acceptable
• have any medical conditions, medical history, or are taking any medications that are contraindicated in the dabigatran etexilate or rosuvastatin label
• are intending to use over-the-counter or prescription medication, including dietary supplements, traditional medicines, and herbal supplements, within 14 days prior to dosing and until study discharge (apart from occasional acetaminophen, hormonal contraception, or hormone replacement therapy)
• currently use or show evidence of substance abuse (including alcohol abuse) or dependence within the past 6 months based on history at screening
• Part 1 Only: have known bleeding disorder including prior personal or familial history of abnormal bleeding, hereditary or acquired coagulation or platelet disorder or abnormal coagulation test (prothrombin time/international normalized ratio [INR] or partial thromboplastin time/activated partial thromboplastin time greater than upper limit of normal [ULN]) result at screening
• Part 2 only: have c.34AA, c.421AA, or c.34GA/421CA genotypes of ABCG2 as determined through genotyping

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 150 Milligram (mg) Dabigatran Etexilate + 200mg Lasmiditan - Part 1; Participants received 150 mg dabigatran etexilate on Day 1 followed by 200 mg lasmiditan once daily (QD) on Days 8 and 9, and 150 mg of dabigatran etexilate along with 200 mg lasmiditan on Day 10. All treatments were administered orally	Drug: Lasmiditan; Administered orally.; Other Names: LY573144; Drug: Dabigatran Etexilate; Administered orally.
Experimental: 10 mg Rosuvastatin + 200 mg Lasmiditan - Part 2; Participants received 10 mg rosuvastatin on Day 1 followed by 200 mg lasmiditan QD on Days 8 and 9, and 10 mg of rosuvastatin along with 200 mg lasmiditan on Day 10. All treatments were administered orally.	Drug: Lasmiditan; Administered orally.; Other Names: LY573144; Drug: Rosuvastatin; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 Pharmacokinetics (PK): Maximum Concentration (Cmax) of Dabigatran to Assess P-glycoprotein (P-gp) Activity.	PK: Cmax of Dabigatran.	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours post-dose.
Part 2 PK: Cmax of Rosuvastatin to Assess Breast Cancer Resistance Protein (BCRP) Activity.	PK: Cmax of Rosuvastatin.	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 hours post-dose.
Part 1 PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞] ) of Dabigatran to Assess P-gp Activity.	PK: AUC[0-∞] of Dabigatran	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 hours post-dose.
Part 2 PK: AUC[0-∞] of Rosuvastatin to Assess BCRP Activity.	PK: AUC[0-∞] of Rosuvastatin	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 hours post-dose.

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2021
• Primary Completion (Actual): July 6, 2021
• Study Completion (Actual): July 6, 2021

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 11, 2021

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: May 21, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Drug Interaction Study
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Serotonin Agents; Serotonin Receptor Agonists; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran; Rosuvastatin Calcium; Lasmiditan
• Other Study ID Numbers: 17573; H8H-MC-LAIO (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No