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CompletedNCT03270644Updated Dec 16, 2019Results posted

A Study of Lasmiditan and Propranolol in Healthy Participants

A Phase 1 interventional study of Lasmiditan and Propranolol in Healthy, sponsored by Eli Lilly and Company. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-12-16.

Sponsored by Eli Lilly and Company · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
44
Allocation
Non-randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This study will assess the effects on heart rate and blood pressure when a single dose of lasmiditan is administered with a daily dose of propranolol. This study will also measure how much lasmiditan gets into the bloodstream after taking lasmiditan alone and after taking it together with propranolol. The study will also look at how well both drugs are tolerated. Information about any side effects that may occur will be collected.

This study will last approximately 45 days including screening. This study will require 13 days/12 nights in a Clinical Research Unit (CRU) followed by 1 follow-up appointment approximately 7 days after the last dose. Screening is required within 28 days prior to the start of the study.

This study is for research purposes only and is not intended to treat any medical condition.

02

Conditions studied

  • Healthy
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Healthy males or females, as determined by medical history and physical examination
  • Have a body mass index (BMI) of 19 to 35 kilograms per meter squared (kg/m²) inclusive, at the time of screening

Exclusion criteria

Exclusion Criteria:

  • Have known allergies to lasmiditan, propranolol, related compounds or any components of the formulation of lasmiditan or propranolol
  • Have a history of, or electrocardiogram (ECG) findings of, clinically significant bradycardia, heart block, tachy or brady arrhythmias, sick sinus syndrome/sinoatrial block, or second or third-degree heart block, or have any other abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study
  • Have an abnormal supine blood pressure, defined as systolic blood pressure less than (\<) 95 or greater than (>) 140 millimeters of mercury (mmHg) or diastolic blood pressure \<65 or >90 mmHg at screening
  • Have a supine pulse rate of \<50 or >90 beats per minute (bpm) at screening
  • Have an estimated glomerular filtration rate (eGFR) of \<60 milliliter per minute (mL/min) per 1.73 meter squared (m2)
  • Show evidence of significant active neuropsychiatric disease (for example, manic depressive illness, schizophrenia, depression)
  • Show a history of central nervous system (CNS) conditions such as strokes, transient ischaemic attacks, significant head trauma, CNS infections, migraines, brain surgery or any other neurological conditions that, in the opinion of the investigator, increases the risk of participating in the study
  • Are women with a positive pregnancy test or women who are lactating
04

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
44 participants (actual)

Study arms

  • Experimental
    Lasmiditan Reference

    Single oral dose of lasmiditan 200 mg on Day 1 as reference treatment.

    Drug: Lasmiditan

  • Active comparator
    Propranolol Reference

    Twice-daily oral doses of propranolol 80 mg on Days 4-10 as reference treatment.

    Drug: Propranolol

  • Experimental
    Lasmiditan + Propranolol Test

    Single oral dose of lasmiditan 200 mg + two oral doses of propranolol 80 mg on Day 9 as test treatment.

    Drug: Lasmiditan · Drug: Propranolol

Interventions

  • DrugLasmiditan

    Administered orally

    Also known as: LY573144

  • DrugPropranolol

    Administered orally

05

What researchers measure

Primary outcomes

  1. Change From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan

    Change from baseline in mean hourly heart rate recorded as beats per minute and collected by Holter ambulatory monitoring in response to propranolol administered alone and in combination with lasmiditan.

    Time frame: Baseline (Day 8), Day 9

Secondary outcomes

  1. Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol

    Maximum concentration of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.

  2. Pharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan

    Maximum concentration of propranolol when administered alone on Day 8 and when coadministered with lasmiditan on Day 9.

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose

  3. Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-tlast)] of Lasmiditan Alone and When Administered With Propranolol

    AUC versus time curve (AUC 0-tlast) of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.

  4. Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan

    AUC versus time curve of propranolol during one dosing interval when administered alone on Day 8 and when administered with lasmiditan on Day 9.

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose

  5. Change From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan

    Change from baseline in PR interval, the interval between the P wave and the QRS complex calculated from electrocardiogram (ECG) data.

    Time frame: Baseline (Day 8), Day 9

  6. Change From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan

    Change from baseline in systolic blood pressure was measured in supine position.

    Time frame: Baseline (Day 8), Day 9

  7. Change From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan

    Change from baseline in diastolic blood pressure was measured in supine position.

    Time frame: Baseline (Day 8), Day 9

06

Results

Posted Dec 2, 2019

Participant flow

Day 1 Lasmiditan Reference
Participant flow — Day 1 Lasmiditan Reference
MilestoneLasmiditan (R); Propranolol (R) + Lasmiditan (T)
Started44
Received at least one dose of study drug44
Completed43
Not completed1
Withdrew: Physician decision1
Day 4 - 10 Propranolol Reference
Participant flow — Day 4 - 10 Propranolol Reference
MilestoneLasmiditan (R); Propranolol (R) + Lasmiditan (T)
Started43
Received at least one dose of study drug43
Day 9 lasmiditan + propranolol test42
Completed42
Not completed1
Withdrew: Adverse event1

Outcome measures

PrimaryChange From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan

Change from baseline in mean hourly heart rate recorded as beats per minute and collected by Holter ambulatory monitoring in response to propranolol administered alone and in combination with lasmiditan.

Time frame:
Baseline (Day 8), Day 9
Reported as:
Mean · beats per minute (bpm)
Change From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan
beats per minute (bpm)Propranolol (Reference Treatment)Lasmiditan + Propranolol (Test Treatment)
Change From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan59.7 ± 7.154.2 ± 5.8
Statistical analysis
  • Propranolol (Reference Treatment) vs Lasmiditan + Propranolol (Test Treatment) · Difference of lsmeans: -5.45 · 90% CI -7.27 to -3.64
SecondaryPharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol

Maximum concentration of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.

Time frame:
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Reported as:
Geometric mean · nanogram per mililiter (ng/mL)
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol
nanogram per mililiter (ng/mL)Lasmiditan (Reference Treatment)Lasmiditan + Propranolol (Test Treatment)
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol323 ± 43290 ± 31
Statistical analysis
  • Lasmiditan (Reference Treatment) vs Lasmiditan + Propranolol (Test Treatment) · Ratio of geometric lsmeans: 0.884 · 90% CI 0.832 to 0.939
SecondaryPharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan

Maximum concentration of propranolol when administered alone on Day 8 and when coadministered with lasmiditan on Day 9.

Time frame:
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Reported as:
Geometric mean · ng/mL
Pharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan
ng/mLPropranolol (Reference Treatment)Lasmiditan + Propranolol (Test Treatment)
Pharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan133 ± 52127 ± 43
Statistical analysis
  • Propranolol (Reference Treatment) vs Lasmiditan + Propranolol (Test Treatment) · Ratio of geometric lsmeans: 0.958 · 90% CI 0.917 to 1.00
SecondaryPharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-tlast)] of Lasmiditan Alone and When Administered With Propranolol

AUC versus time curve (AUC 0-tlast) of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.

Time frame:
Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.
Reported as:
Geometric mean · nanograms * hour/mL (ng*h/mL)
Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-tlast)] of Lasmiditan Alone and When Administered With Propranolol
nanograms * hour/mL (ng*h/mL)Lasmiditan (Reference Treatment)Lasmiditan + Propranolol (Test Treatment)
Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Last Measurable Concentration [AUC(0-tlast)] of Lasmiditan Alone and When Administered With Propranolol2100 ± 392160 ± 30
Statistical analysis
  • Lasmiditan (Reference Treatment) vs Lasmiditan + Propranolol (Test Treatment) · Ratio of geometric lsmeans: 1.01 · 90% CI 0.967 to 1.04
SecondaryPharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan

AUC versus time curve of propranolol during one dosing interval when administered alone on Day 8 and when administered with lasmiditan on Day 9.

Time frame:
Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Reported as:
Geometric mean · ng*hr/mL
Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan
ng*hr/mLPropranolol (Reference Treatment)Lasmiditan + Propranolol (Test Treatment)
Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan910 ± 50910 ± 43
Statistical analysis
  • Propranolol (Reference Treatment) vs Lasmiditan + Propranolol (Test Treatment) · Ratio of geometric lsmeans: 0.999 · 90% CI 0.967 to 1.03
SecondaryChange From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan

Change from baseline in PR interval, the interval between the P wave and the QRS complex calculated from electrocardiogram (ECG) data.

Time frame:
Baseline (Day 8), Day 9
Reported as:
Mean · millisecond (msec)
Change From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan
millisecond (msec)Propranolol (Reference Treatment)Lasmiditan + Propranolol (Test Treatment)
Change From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan165.6 ± 20.5161.9 ± 20.3
Statistical analysis
  • Propranolol (Reference Treatment) vs Lasmiditan + Propranolol (Test Treatment) · Difference of lsmeans: -3.51 · 90% CI -6.39 to -0.64
SecondaryChange From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan

Change from baseline in systolic blood pressure was measured in supine position.

Time frame:
Baseline (Day 8), Day 9
Reported as:
Mean · millimeters of mercury (mmHg)
Change From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan
millimeters of mercury (mmHg)Propranolol (Reference Treatment)Lasmiditan + Propranolol (Test Treatment)
Change From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan106.9 ± 6.6112.4 ± 10.9
Statistical analysis
  • Propranolol (Reference Treatment) vs Lasmiditan + Propranolol (Test Treatment) · Difference of lsmeans: 5.57 · 90% CI 3.57 to 7.57
SecondaryChange From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan

Change from baseline in diastolic blood pressure was measured in supine position.

Time frame:
Baseline (Day 8), Day 9
Reported as:
Mean · mmHg
Change From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan
mmHgPropranolol (Reference Treatment)Lasmiditan + Propranolol (Test Treatment)
Change From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan64.0 ± 6.267.4 ± 7.8
Statistical analysis
  • Propranolol (Reference Treatment) vs Lasmiditan + Propranolol (Test Treatment) · Difference of lsmeans: 3.47 · 90% CI 1.99 to 4.95

Adverse events

Collected over Baseline through study completion (up to 23 days).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Lasmiditan 200 mg (Reference Treatment)0/44 (0%)0/44 (0%)9/44 (20.5%)
Propranolol 80 mg (Reference Treatment)0/43 (0%)1/43 (2.3%)1/43 (2.3%)
Lasmiditan 200 mg + Propranolol 80 mg (Test Treatment)0/42 (0%)0/42 (0%)7/42 (16.7%)
Most frequent serious events
Most frequent serious events
EventLasmiditan 200 mg (Reference Treatment)Propranolol 80 mg (Reference Treatment)Lasmiditan 200 mg + Propranolol 80 mg (Test Treatment)
Anal abscessInfections and infestations0/441/430/42
Most frequent other events
Most frequent other events
EventLasmiditan 200 mg (Reference Treatment)Propranolol 80 mg (Reference Treatment)Lasmiditan 200 mg + Propranolol 80 mg (Test Treatment)
DizzinessNervous system disorders6/441/434/42
NauseaGastrointestinal disorders0/440/433/42
FatigueGeneral disorders2/440/433/42
ParaesthesiaNervous system disorders3/440/430/42

Baseline characteristics

All participants who received at least one dose of study drug.

Age, Continuous
Age, Continuous(years)Lasmiditan + Propranolol
Mean41.1 ± 12.8
Sex: Female, Male
Sex: Female, Male(Participants)Lasmiditan + Propranolol
Female12
Male32
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Lasmiditan + Propranolol
Hispanic or Latino20
Not Hispanic or Latino24
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Lasmiditan + Propranolol
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American15
White28
More than one race0
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(Participants)Lasmiditan + Propranolol
United States44
Mean Hourly Heart Rate
Mean Hourly Heart Rate(beats per minute (BPM))Lasmiditan + Propranolol
Mean59.7 ± 7.1
07

Study locations

1 site
  • Covance Daytona Beach
    Daytona Beach, Florida 32117, United States
08

References and documents

Study documents

  • Study protocol · Oct 20, 2017
  • Statistical analysis plan · Nov 22, 2017

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03270644
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
Sep 1, 2017
Start date
Aug 31, 2017
Primary completion
Nov 22, 2017
Completion
Nov 22, 2017
Results posted
Dec 2, 2019
Last update
Dec 16, 2019

Study contacts

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)
study director · Eli Lilly and Company

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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