Trial Outcomes & Findings for A Study of Lasmiditan and Propranolol in Healthy Participants (NCT NCT03270644)
NCT ID: NCT03270644
Last Updated: 2019-12-16
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
44 participants
Primary outcome timeframe
Baseline (Day 8), Day 9
Results posted on
2019-12-16
Participant Flow
Open-label fixed-sequence study in which participants received a single oral dose of lasmiditan 200 mg on Day (D) 1 Reference Treatment (R), then propranolol 80 mg administered orally twice daily from Day 4 through Day 10 Reference Treatment, with one single oral dose of lasmiditan 200 mg on Day 9 Test Treatment (T).
Participant milestones
| Measure |
Lasmiditan (R); Propranolol (R) + Lasmiditan (T)
Lasmiditan 200 mg single dose administered orally on D 1 (Reference); Propranolol 80 mg administered orally twice daily D4-10(Reference); Lasmiditan 200 mg administered orally on D9 (Test).
|
|---|---|
|
Day 1 Lasmiditan Reference
STARTED
|
44
|
|
Day 1 Lasmiditan Reference
Received at Least One Dose of Study Drug
|
44
|
|
Day 1 Lasmiditan Reference
COMPLETED
|
43
|
|
Day 1 Lasmiditan Reference
NOT COMPLETED
|
1
|
|
Day 4 - 10 Propranolol Reference
STARTED
|
43
|
|
Day 4 - 10 Propranolol Reference
Received at Least One Dose of Study Drug
|
43
|
|
Day 4 - 10 Propranolol Reference
Day 9 Lasmiditan + Propranolol Test
|
42
|
|
Day 4 - 10 Propranolol Reference
COMPLETED
|
42
|
|
Day 4 - 10 Propranolol Reference
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Lasmiditan (R); Propranolol (R) + Lasmiditan (T)
Lasmiditan 200 mg single dose administered orally on D 1 (Reference); Propranolol 80 mg administered orally twice daily D4-10(Reference); Lasmiditan 200 mg administered orally on D9 (Test).
|
|---|---|
|
Day 1 Lasmiditan Reference
Physician Decision
|
1
|
|
Day 4 - 10 Propranolol Reference
Adverse Event
|
1
|
Baseline Characteristics
All participants who received one dose of study drug and had hourly HR baseline data.
Baseline characteristics by cohort
| Measure |
Lasmiditan + Propranolol
n=44 Participants
Single 200 mg dose of lasmiditan administered orally on Day 1, then 80mg propranolol twice per day administered orally on Days 4 through 10, and 200 mg lasmiditan coadministered orally with propranolol on Day 9.
|
|---|---|
|
Age, Continuous
|
41.1 years
STANDARD_DEVIATION 12.8 • n=44 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=44 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
20 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=44 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Black or African American
|
15 Participants
n=44 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=44 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=44 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=44 Participants
|
|
Region of Enrollment
United States
|
44 Participants
n=44 Participants
|
|
Mean Hourly Heart Rate
|
59.7 beats per minute (BPM)
STANDARD_DEVIATION 7.1 • n=42 Participants • All participants who received one dose of study drug and had hourly HR baseline data.
|
PRIMARY outcome
Timeframe: Baseline (Day 8), Day 9Population: All participants who had at least one dose of study drug and had baseline and post-baseline cardiovascular measurements.
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.
Outcome measures
| Measure |
Propranolol (Reference Treatment)
n=42 Participants
Propranolol 80 mg administered orally twice daily on Day 8.
|
Lasmiditan + Propranolol (Test Treatment)
n=42 Participants
Lasmiditan 200 mg coadministered with propranolol 80 mg on Day 9.
|
|---|---|---|
|
Change From Baseline (Day 8) in Mean Hourly Heart Rate Following Propranolol Administered Alone and When Coadministered With Lasmiditan
|
59.7 beats per minute (bpm)
Standard Deviation 7.1
|
54.2 beats per minute (bpm)
Standard Deviation 5.8
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.Population: All participants who received at least one dose of study drug and have evaluable PK data.
Maximum concentration of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.
Outcome measures
| Measure |
Propranolol (Reference Treatment)
n=44 Participants
Propranolol 80 mg administered orally twice daily on Day 8.
|
Lasmiditan + Propranolol (Test Treatment)
n=42 Participants
Lasmiditan 200 mg coadministered with propranolol 80 mg on Day 9.
|
|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Lasmiditan Alone and When Coadministered With Propranolol
|
323 nanogram per mililiter (ng/mL)
Geometric Coefficient of Variation 43
|
290 nanogram per mililiter (ng/mL)
Geometric Coefficient of Variation 31
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dosePopulation: All participants who received at least one dose of study drug and have evaluable PK data.
Maximum concentration of propranolol when administered alone on Day 8 and when coadministered with lasmiditan on Day 9.
Outcome measures
| Measure |
Propranolol (Reference Treatment)
n=42 Participants
Propranolol 80 mg administered orally twice daily on Day 8.
|
Lasmiditan + Propranolol (Test Treatment)
n=42 Participants
Lasmiditan 200 mg coadministered with propranolol 80 mg on Day 9.
|
|---|---|---|
|
Pharmacokinetic: Maximum Observed Drug Concentration (Cmax) of Propranolol Alone and When Coadministered With Lasmiditan
|
133 ng/mL
Geometric Coefficient of Variation 52
|
127 ng/mL
Geometric Coefficient of Variation 43
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose.Population: All participants who received at least one dose of study drug and have evaluable PK data.
AUC versus time curve (AUC 0-tlast) of lasmiditan when administered alone on Day 1 and when coadministered with propranolol on Day 9.
Outcome measures
| Measure |
Propranolol (Reference Treatment)
n=44 Participants
Propranolol 80 mg administered orally twice daily on Day 8.
|
Lasmiditan + Propranolol (Test Treatment)
n=42 Participants
Lasmiditan 200 mg coadministered with propranolol 80 mg on Day 9.
|
|---|---|---|
|
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
|
2100 nanograms * hour/mL (ng*h/mL)
Geometric Coefficient of Variation 39
|
2160 nanograms * hour/mL (ng*h/mL)
Geometric Coefficient of Variation 30
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dosePopulation: All participants who received at least one dose of study drug and have evaluable PK data.
AUC versus time curve of propranolol during one dosing interval when administered alone on Day 8 and when administered with lasmiditan on Day 9.
Outcome measures
| Measure |
Propranolol (Reference Treatment)
n=42 Participants
Propranolol 80 mg administered orally twice daily on Day 8.
|
Lasmiditan + Propranolol (Test Treatment)
n=42 Participants
Lasmiditan 200 mg coadministered with propranolol 80 mg on Day 9.
|
|---|---|---|
|
Pharmacokinetic: Area Under the Concentration Versus Time Curve (AUC) of Propranolol During One Dosing Interval Alone and When Administered With Lasmiditan
|
910 ng*hr/mL
Geometric Coefficient of Variation 50
|
910 ng*hr/mL
Geometric Coefficient of Variation 43
|
SECONDARY outcome
Timeframe: Baseline (Day 8), Day 9Population: All participants who had at least one dose of study drug and had evaluable baseline and post-baseline cardiovascular measurements.
Change from baseline in PR interval, the interval between the P wave and the QRS complex calculated from electrocardiogram (ECG) data.
Outcome measures
| Measure |
Propranolol (Reference Treatment)
n=42 Participants
Propranolol 80 mg administered orally twice daily on Day 8.
|
Lasmiditan + Propranolol (Test Treatment)
n=41 Participants
Lasmiditan 200 mg coadministered with propranolol 80 mg on Day 9.
|
|---|---|---|
|
Change From Baseline (Day 8) in PR Interval Following Propranolol Administered Alone and When Coadministered With Lasmiditan
|
165.6 millisecond (msec)
Standard Deviation 20.5
|
161.9 millisecond (msec)
Standard Deviation 20.3
|
SECONDARY outcome
Timeframe: Baseline (Day 8), Day 9Population: All participants who had at least one dose of study drug and had evaluable baseline and post-baseline cardiovascular measurements.
Change from baseline in systolic blood pressure was measured in supine position.
Outcome measures
| Measure |
Propranolol (Reference Treatment)
n=42 Participants
Propranolol 80 mg administered orally twice daily on Day 8.
|
Lasmiditan + Propranolol (Test Treatment)
n=42 Participants
Lasmiditan 200 mg coadministered with propranolol 80 mg on Day 9.
|
|---|---|---|
|
Change From Baseline (Day 8) in Systolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan
|
106.9 millimeters of mercury (mmHg)
Standard Deviation 6.6
|
112.4 millimeters of mercury (mmHg)
Standard Deviation 10.9
|
SECONDARY outcome
Timeframe: Baseline (Day 8), Day 9Population: All participants who had at least one dose of study drug and had evaluable baseline and post-baseline cardiovascular measurements.
Change from baseline in diastolic blood pressure was measured in supine position.
Outcome measures
| Measure |
Propranolol (Reference Treatment)
n=42 Participants
Propranolol 80 mg administered orally twice daily on Day 8.
|
Lasmiditan + Propranolol (Test Treatment)
n=42 Participants
Lasmiditan 200 mg coadministered with propranolol 80 mg on Day 9.
|
|---|---|---|
|
Change From Baseline (Day 8) in Diastolic Blood Pressure Following Propranolol Administered Alone and When Coadministered With Lasmiditan
|
64.0 mmHg
Standard Deviation 6.2
|
67.4 mmHg
Standard Deviation 7.8
|
Adverse Events
Lasmiditan 200 mg (Reference Treatment)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Propranolol 80 mg (Reference Treatment)
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Lasmiditan 200 mg + Propranolol 80 mg (Test Treatment)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lasmiditan 200 mg (Reference Treatment)
n=44 participants at risk
Lasmiditan 200 mg single dose administered orally on Day 1.
|
Propranolol 80 mg (Reference Treatment)
n=43 participants at risk
Propranolol 80 mg administered orally twice daily on Day 4 to Day 10.
|
Lasmiditan 200 mg + Propranolol 80 mg (Test Treatment)
n=42 participants at risk
Lasmiditan 200 mg coadministered orally with propranolol 80 mg on Day 9.
|
|---|---|---|---|
|
Infections and infestations
Anal abscess
|
0.00%
0/44 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
2.3%
1/43 • Number of events 1 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
0.00%
0/42 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
Other adverse events
| Measure |
Lasmiditan 200 mg (Reference Treatment)
n=44 participants at risk
Lasmiditan 200 mg single dose administered orally on Day 1.
|
Propranolol 80 mg (Reference Treatment)
n=43 participants at risk
Propranolol 80 mg administered orally twice daily on Day 4 to Day 10.
|
Lasmiditan 200 mg + Propranolol 80 mg (Test Treatment)
n=42 participants at risk
Lasmiditan 200 mg coadministered orally with propranolol 80 mg on Day 9.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/44 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
0.00%
0/43 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
7.1%
3/42 • Number of events 3 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
|
General disorders
Fatigue
|
4.5%
2/44 • Number of events 2 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
0.00%
0/43 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
7.1%
3/42 • Number of events 3 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
|
Nervous system disorders
Dizziness
|
13.6%
6/44 • Number of events 8 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
2.3%
1/43 • Number of events 1 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
9.5%
4/42 • Number of events 4 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
|
Nervous system disorders
Paraesthesia
|
6.8%
3/44 • Number of events 3 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
0.00%
0/43 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
0.00%
0/42 • Baseline through study completion (up to 23 days).
All participants who have received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60