Clinical trial NCT03040362: Absorption, Metabolism and Excretion of [14C]-Lasmiditan - Single Oral Dose Administration
Official title: A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-Lasmiditan Following Single Oral Dose Administration in Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: CoLucid Pharmaceuticals
First posted: 2017-02-02
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This study will be an open-label, nonrandomized, absorption, metabolism, and excretion study of \[14C\]-lasmiditan administered as a 200-milligrams (mg) (approximately 100 microcuries\[µCi\]) oral solution to 8 healthy males and females, following at least a 10 hour fast from food to assess the pharmacokinetics (PK), metabolism, and routes and extent of elimination of a single oral dose of 200 mg (approximately 100 µCi) \[14C\] lasmiditan in healthy males and females.


Eligibility criteria: Inclusion Criteria:

* Males and females, between 18 and 60 years of age, inclusive, at Screening
* Have a body mass index range of 18.5 to 32.0 kilograms per meter squared (kg/m²), inclusive, at Screening
* In good health, determined by no clinically significant findings from medical history, 12 lead electrocardiogram (ECG), and vital signs measurements at Screening or Check-in (Day 1) as determined by the Investigator (or designee)
* Clinical laboratory evaluations (including clinical chemistry panel \[fasted at least 10 hours\], hematology/complete blood count \[CBC\], and urinalysis \[UA\]; within the reference range for the test laboratory at Screening and Check-in, unless deemed not clinically significant by the Investigator (or designee)
* Negative test for selected drugs of abuse at Screening (does not include alcohol) and at Check-in (does include alcohol)
* Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C virus antibody and negative human immunodeficiency virus (HIV) antibody screens
* Females must be nonpregnant, nonlactating, and either postmenopausal (defined as no menstrual period for at least 12 months and confirmed by a serum follicle-stimulating hormone (FSH) level of ≥40 milli-international units (mIU/mL), surgically sterile (e.g., bilateral oophorectomy, salpingectomy, and/or hysterectomy) for at least 90 days prior to Screening, or must have undergone bilateral tubal ligation and agree to use effective contraception. For all females, the pregnancy test results must be negative at Screening and Check-in
* Males will be surgically sterile for at least 90 days prior to Screening or when sexually-active with female partners of child-bearing potential will agree to use contraception from Check-in until 90 days following Discharge. Male participants must also be willing to refrain from donating sperm from Check-in until 90 days following Discharge
* Able to comprehend and willing to sign an informed consent form (ICF)
* A minimum of 1 to 2 bowel movements per day

Exclusion Criteria:

* Significant history or clinical manifestation of any metabolic, allergic, infectious, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator \[or designee\]) prior to Check-in
* History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) prior to Check-in
* History of stomach or intestinal surgery or resection that could alter absorption or excretion of orally administered drugs prior to Check-in, except that cholecystectomy, appendectomy, and hernia repair will be allowed if it was not associated with complications
* History or presence of an abnormal ECG that, in the Investigator's (or designee's) opinion, is clinically significant at Screening or Check-in
* History of orthostatic hypotension with or without syncope
* A sustained seated systolic blood pressure \>150 millimeters of mercury (mmHg) or \<90 mmHg or a diastolic blood pressure \>90 mmHg or \<50 mmHg at Screening or Check in. Blood pressure may be retested twice at intervals of 5 minutes. The out of range blood pressure values will be considered sustained if either the systolic or diastolic blood pressures are outside the stated limits after these 3 assessments
* History of alcoholism or drug addiction within 1 year prior to Check-in
* Use of any tobacco- or nicotine-containing products (including but not limited to cigarettes, e-cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to Check-in, or positive cotinine screen at Screening or Check-in
* Participation in more than 1 other radiolabeled investigational study drug trial within 12 months prior to Check-in. The previous radiolabeled study drug must have been received more than 6 months prior to Check-in for this study and the total exposure from this study and the previous study will be within the recommended levels considered safe, per United States (US) Title 21 Code of Federal Regulations (CFR) 361.1 (e.g., less than 5,000 millirem \[mrem\] whole body annual exposure)
* Exposure to significant radiation (e.g., serial x-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) within 12 months prior to Check-in
* Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half-lives (if known) or 30 days prior to Check-in, whichever is longer
* Use of any prescription medications/products within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee)
* Use of any over-the-counter, nonprescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior to Check-in, unless deemed acceptable by the Investigator (or designee)
* Poor peripheral venous access prior to Check-in
* Donation of whole blood from 56 days prior to Screening through Discharge, inclusive, or of plasma from 30 days prior to Screening through Discharge, inclusive
* Receipt of blood products within 2 months prior to Check-in
* Participant is at imminent risk of suicide (positive response to question 4 or 5 on the baseline Columbia-Suicide Severity Rating Scale (C-SSRS) or had a suicide attempt within 6 months prior to Screening
* Any acute or chronic condition that, in the opinion of the Investigator (or designee), would limit the particpant's ability to complete or participate in this clinical study
* Any other unspecified reason that, in the opinion of the Investigator (or designee) or Sponsor, makes the participant unsuitable for enrollment

Primary outcomes:
measure: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose
measure: Pharmacokinetics: Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours pos-tdose
measure: Pharmacokinetics: Area Under the Concentration Versus Time Curve From Zero to Tlast (AUC[0-tlast])
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose
measure: AUC Time Zero to Infinity (AUC0-∞) Blood/Plasma Ratio
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours post-dose
measure: AUC Time Zero to Infinity (AUC0-∞) Plasma Lasmiditan/Total Radioactivity Ratio
timeFrame: Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours pos-tdose
Secondary outcomes:
measure: Pharmacokinetics - Cumulative Amount of Lasmiditan and Its Metabolites Excreted in Urine
timeFrame: Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose
measure: Percentage of Lasmiditan Recovered in Urine, Relative to Dose Administered
timeFrame: Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose
measure: Renal Clearance (CLR)
timeFrame: Pre-dose (-12 to 0 hours) and intervals: 0 to 6, 6 to 12, 12 to 24, 24 to 48, 48 to 72, 72 to 96, 96 to 120, 120 to 144, 144 to 168, and 168 to 192 hours post-dose
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 49 days
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance Clinical Research Unit
state: Wisconsin
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: