Trial Outcomes & Findings for A Drug-drug Interaction Study of Lanabecestat (LY3314814) in Healthy Participants (NCT NCT02568397)
NCT ID: NCT02568397
Last Updated: 2019-11-01
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
60 participants
Primary outcome timeframe
Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose
Results posted on
2019-11-01
Participant Flow
Participant milestones
| Measure |
Dabigatran Etexilate
Single dose of dabigatran etexilate administered orally on Day 1.
|
LY3314814 + Dabigatran Etexilate
Single dose of LY3314814 administered orally once daily on Days 3 to 21. Single doses of dabigatran etexilate administered orally on Days 16 and 20 during the LY3314814 dosing
|
|---|---|---|
|
Period 1
STARTED
|
60
|
0
|
|
Period 1
Received at Least 1 Dose of Study Drug
|
60
|
0
|
|
Period 1
COMPLETED
|
60
|
0
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
0
|
60
|
|
Period 2
COMPLETED
|
0
|
58
|
|
Period 2
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Dabigatran Etexilate
Single dose of dabigatran etexilate administered orally on Day 1.
|
LY3314814 + Dabigatran Etexilate
Single dose of LY3314814 administered orally once daily on Days 3 to 21. Single doses of dabigatran etexilate administered orally on Days 16 and 20 during the LY3314814 dosing
|
|---|---|---|
|
Period 2
Withdrawal by Subject
|
0
|
1
|
|
Period 2
Physician Decision
|
0
|
1
|
Baseline Characteristics
A Drug-drug Interaction Study of Lanabecestat (LY3314814) in Healthy Participants
Baseline characteristics by cohort
| Measure |
Overall
n=60 Participants
Overall study population
|
|---|---|
|
Age, Continuous
|
36.1 years
STANDARD_DEVIATION 7.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
52 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
31 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
60 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdosePopulation: All participants who received at least one dose of study drug and have evaluable pharmacokinetic (PK) data.
Outcome measures
| Measure |
LY3314814 and Dabigatran Etexilate Day 20
n=54 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21.Single dose of dabigatran etexilate administered orally 4 hours after LY3314814 administration on Day 20.
|
LY3314814 (AZD3293)
n=60 Participants
50 mg LY3314814 administered orally alone on Day 15.
|
LY3314814 and Dabigatran Etexilate Day 16
n=56 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21. Concurrent single dose of dabigatran etexilate administered orally on day 16.
|
|---|---|---|---|
|
Pharmacokinetics (PK) : Maximum Concentration (Cmax) of Dabigatran
|
138 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 46
|
128 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 69
|
148 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 56
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdosePopulation: All participants who received at least one dose of study drug and had evaluable PK data.
Outcome measures
| Measure |
LY3314814 and Dabigatran Etexilate Day 20
n=54 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21.Single dose of dabigatran etexilate administered orally 4 hours after LY3314814 administration on Day 20.
|
LY3314814 (AZD3293)
n=60 Participants
50 mg LY3314814 administered orally alone on Day 15.
|
LY3314814 and Dabigatran Etexilate Day 16
n=56 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21. Concurrent single dose of dabigatran etexilate administered orally on day 16.
|
|---|---|---|---|
|
Pharmacokinetics: Area Under The Dabigatran Pharmacokinetic (PK) Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity)
|
1110 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 44
|
1090 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 61
|
1240 nanogram*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 53
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdosePopulation: All participants who received one dose of study drug and had evaluable PK data.
Outcome measures
| Measure |
LY3314814 and Dabigatran Etexilate Day 20
n=56 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21.Single dose of dabigatran etexilate administered orally 4 hours after LY3314814 administration on Day 20.
|
LY3314814 (AZD3293)
n=57 Participants
50 mg LY3314814 administered orally alone on Day 15.
|
LY3314814 and Dabigatran Etexilate Day 16
n=57 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21. Concurrent single dose of dabigatran etexilate administered orally on day 16.
|
|---|---|---|---|
|
Pharmacokinetics: Maximum Concentration (Cmax) of Lanabecestat
|
331 ng/mL
Geometric Coefficient of Variation 21
|
342 ng/mL
Geometric Coefficient of Variation 23
|
315 ng/mL
Geometric Coefficient of Variation 21
|
SECONDARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdosePopulation: All participants who received one dose of study drug and had evaluable PK data.
Outcome measures
| Measure |
LY3314814 and Dabigatran Etexilate Day 20
n=56 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21.Single dose of dabigatran etexilate administered orally 4 hours after LY3314814 administration on Day 20.
|
LY3314814 (AZD3293)
n=57 Participants
50 mg LY3314814 administered orally alone on Day 15.
|
LY3314814 and Dabigatran Etexilate Day 16
n=57 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21. Concurrent single dose of dabigatran etexilate administered orally on day 16.
|
|---|---|---|---|
|
Pharmacokinetics: Area Under the Lanabecestat Pharmacokinetic (PK) Concentration Versus Time Curve During One Dosing Interval (24 Hours) (AUCtau)
|
3490 ng*h/mL
Geometric Coefficient of Variation 24
|
3360 ng*h/mL
Geometric Coefficient of Variation 25
|
3300 ng*h/mL
Geometric Coefficient of Variation 26
|
SECONDARY outcome
Timeframe: Days 1, 16 and 20: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdosePopulation: All participants who received at least one dose of study drug and had evaluable Pharmacodynamic (PD) data.
Outcome measures
| Measure |
LY3314814 and Dabigatran Etexilate Day 20
n=49 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21.Single dose of dabigatran etexilate administered orally 4 hours after LY3314814 administration on Day 20.
|
LY3314814 (AZD3293)
n=57 Participants
50 mg LY3314814 administered orally alone on Day 15.
|
LY3314814 and Dabigatran Etexilate Day 16
n=55 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21. Concurrent single dose of dabigatran etexilate administered orally on day 16.
|
|---|---|---|---|
|
Pharmacodynamics: Area Under the Effect Versus Time Curve (AUEC) of Thrombin Time
|
2030 seconds*hour (s*h)
Standard Deviation 518
|
2080 seconds*hour (s*h)
Standard Deviation 517
|
2170 seconds*hour (s*h)
Standard Deviation 611
|
SECONDARY outcome
Timeframe: Days 1, 16 and 20: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdosePopulation: All participants who received at least one dose of study drug and had evaluable Pharmacodynamic (PD) data.
Ratio of maximum effect to baseline effect following administration of 150 mg dabigatran etexilate alone on Day 1, 50 mg LY3314814 and 150 mg dabigatran dosed concurrently on Day 16, and 50 mg LY3314814 and 150 mg dabigatran (dosed 4 hours later) on Day 20
Outcome measures
| Measure |
LY3314814 and Dabigatran Etexilate Day 20
n=32 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21.Single dose of dabigatran etexilate administered orally 4 hours after LY3314814 administration on Day 20.
|
LY3314814 (AZD3293)
n=42 Participants
50 mg LY3314814 administered orally alone on Day 15.
|
LY3314814 and Dabigatran Etexilate Day 16
n=42 Participants
Single dose of LY3314814 administered orally once daily on Days 3 to 21. Concurrent single dose of dabigatran etexilate administered orally on day 16.
|
|---|---|---|---|
|
Pharmacodynamics: Ratio of Maximum Effect to Baseline Effect (ERmax) of Thrombin Time
|
7.00 ratio of maximum effect
Interval 1.1 to 7.95
|
7.10 ratio of maximum effect
Interval 3.49 to 7.84
|
7.09 ratio of maximum effect
Interval 1.06 to 7.84
|
Adverse Events
Dabigatran Etexilate
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
LY3314814 (AZD3293)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
LY3314814 and Dabigatran Etexilate Day 16
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
LY3314814 and Dabigatran Etexilate Day 20
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Dabigatran Etexilate
n=60 participants at risk
Single dose of 150mg dabigatran etexilate administered orally.
|
LY3314814 (AZD3293)
n=60 participants at risk
50 mg LY3314814 administered orally alone on Day 15
|
LY3314814 and Dabigatran Etexilate Day 16
n=58 participants at risk
Single dose of LY3314814 administered orally once daily on Days 3 to 21. Concurrent single dose of dabigatran etexilate administered orally on Day 16.
|
LY3314814 and Dabigatran Etexilate Day 20
n=58 participants at risk
Single dose of LY3314814 administered orally once daily on Days 3 to 21. Concurrent single dose of dabigatran etexilate administered orally on day 20.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/58
|
0.00%
0/58
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/58
|
0.00%
0/58
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/60
|
0.00%
0/60
|
0.00%
0/58
|
1.7%
1/58 • Number of events 1
|
|
General disorders
Asthenia
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/58
|
0.00%
0/58
|
|
General disorders
Chest pain
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/58
|
0.00%
0/58
|
|
General disorders
Fatigue
|
1.7%
1/60 • Number of events 1
|
0.00%
0/60
|
0.00%
0/58
|
0.00%
0/58
|
|
General disorders
Feeling hot
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/58
|
0.00%
0/58
|
|
General disorders
Vessel puncture site haematoma
|
1.7%
1/60 • Number of events 1
|
0.00%
0/60
|
0.00%
0/58
|
0.00%
0/58
|
|
General disorders
Vessel puncture site swelling
|
0.00%
0/60
|
0.00%
0/60
|
1.7%
1/58 • Number of events 1
|
0.00%
0/58
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/60
|
0.00%
0/60
|
0.00%
0/58
|
1.7%
1/58 • Number of events 1
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/60
|
0.00%
0/60
|
0.00%
0/58
|
1.7%
1/58 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.7%
1/60 • Number of events 1
|
0.00%
0/60
|
0.00%
0/58
|
0.00%
0/58
|
|
Nervous system disorders
Dizziness
|
0.00%
0/60
|
3.3%
2/60 • Number of events 2
|
1.7%
1/58 • Number of events 1
|
0.00%
0/58
|
|
Nervous system disorders
Headache
|
0.00%
0/60
|
5.0%
3/60 • Number of events 4
|
0.00%
0/58
|
0.00%
0/58
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/58
|
0.00%
0/58
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/58
|
0.00%
0/58
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/60
|
0.00%
0/60
|
0.00%
0/58
|
1.7%
1/58 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/58
|
1.7%
1/58 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/58
|
0.00%
0/58
|
|
Vascular disorders
Flushing
|
0.00%
0/60
|
1.7%
1/60 • Number of events 1
|
0.00%
0/58
|
0.00%
0/58
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5079
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60