Trial Outcomes & Findings for A Drug-Drug Interaction Study of Lanabecestat (LY3314814) in Healthy Participants (NCT NCT02406261)
NCT ID: NCT02406261
Last Updated: 2019-11-04
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
82 participants
Primary outcome timeframe
Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A)
Results posted on
2019-11-04
Participant Flow
It was planned that all subjects in Cohort B would be enrolled at Site 002.
Participant milestones
| Measure |
Cohort A
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 mcg midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37
|
Cohort B
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2
|
|---|---|---|
|
Period 1
STARTED
|
50
|
32
|
|
Period 1
Received at Least One Dose of Study Drug
|
50
|
32
|
|
Period 1
COMPLETED
|
47
|
32
|
|
Period 1
NOT COMPLETED
|
3
|
0
|
|
Period 2
STARTED
|
0
|
32
|
|
Period 2
COMPLETED
|
0
|
29
|
|
Period 2
NOT COMPLETED
|
0
|
3
|
Reasons for withdrawal
| Measure |
Cohort A
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 mcg midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37
|
Cohort B
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2
|
|---|---|---|
|
Period 1
Lost to Follow-up
|
2
|
0
|
|
Period 1
Adverse Event
|
1
|
0
|
|
Period 2
Physician Decision
|
0
|
1
|
|
Period 2
Protocol Violation
|
0
|
1
|
|
Period 2
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Drug-Drug Interaction Study of Lanabecestat (LY3314814) in Healthy Participants
Baseline characteristics by cohort
| Measure |
Cohort A
n=50 Participants
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37
|
Cohort B
n=32 Participants
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2
|
Total
n=82 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
50 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
82 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
56 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
21 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
28 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
54 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
20 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
27 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
43 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
50 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
82 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A)Population: Participants who received at least one dose of study drug and had evaluable PK data.
Outcome measures
| Measure |
Cohort A
n=50 Participants
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37
|
Cohort B
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2
|
|---|---|---|
|
Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814
|
3200 Nanogram * hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 21
|
—
|
PRIMARY outcome
Timeframe: Day 2 and 36: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (Cohort A)Population: Participants who received at least one dose of study drug and had evaluable PK data.
Outcome measures
| Measure |
Cohort A
n=49 Participants
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37
|
Cohort B
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2
|
|---|---|---|
|
PK Profile for Simvastatin: AUC(0-∞)
AUC(0-∞) Simvastatin Day 2
|
15.1 ng*h/mL
Geometric Coefficient of Variation 84
|
—
|
|
PK Profile for Simvastatin: AUC(0-∞)
AUC(0-∞) Simvastatin Day 36
|
21.2 ng*h/mL
Geometric Coefficient of Variation 59
|
—
|
PRIMARY outcome
Timeframe: Day 1, 3, 17, 35, and 37: Predose, 0.25, 0.5, 1, 2, 3, 5, 8, and 12 hours (Cohort A)Population: Participants who received at least one dose of study drug and had evaluable PK data.
Outcome measures
| Measure |
Cohort A
n=49 Participants
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37
|
Cohort B
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2
|
|---|---|---|
|
PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose
AUC(0-∞) Oral Day 1
|
6.53 ng*h/mL
Geometric Coefficient of Variation 38
|
—
|
|
PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose
AUC(0-∞) Oral Day 17
|
6.24 ng*h/mL
Geometric Coefficient of Variation 42
|
—
|
|
PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose
AUC(0-∞) Oral Day 35
|
5.59 ng*h/mL
Geometric Coefficient of Variation 40
|
—
|
|
PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose
AUC(0-∞) IV Day 3
|
11.4 ng*h/mL
Geometric Coefficient of Variation 22
|
—
|
|
PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose
AUC(0-∞) IV Day 37
|
11.6 ng*h/mL
Geometric Coefficient of Variation 21
|
—
|
PRIMARY outcome
Timeframe: Day 1 and 28: predose 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96,120, 216, 288, and 360 hours (Cohort B)Population: Participants who received at least one dose of study drug and had evaluable PK data.
Outcome measures
| Measure |
Cohort A
n=31 Participants
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37
|
Cohort B
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2
|
|---|---|---|
|
PK Profile for Donepezil: AUC(0-∞)
Day 1
|
271 ng*h/mL
Geometric Coefficient of Variation 28
|
—
|
|
PK Profile for Donepezil: AUC(0-∞)
Day 28
|
285 ng*h/mL
Geometric Coefficient of Variation 23
|
—
|
SECONDARY outcome
Timeframe: Cohort A : Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)Population: Participants who received at least one dose of study drug.
Outcome measures
| Measure |
Cohort A
n=50 Participants
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37
|
Cohort B
n=32 Participants
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2
|
|---|---|---|
|
Number of Participants With One or More Serious Adverse Events(s) Considered by the Investigator to be Related to Study Drug Administration
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Cohort A: Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)Population: Participants who received at least one dose of study drug.
C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.
Outcome measures
| Measure |
Cohort A
n=50 Participants
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37
|
Cohort B
n=32 Participants
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2
|
|---|---|---|
|
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
Suicidal Ideation
|
0 Participants
|
0 Participants
|
|
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
Suicidal Behavior
|
0 Participants
|
0 Participants
|
Adverse Events
Cohort A
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort B
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort A
n=50 participants at risk
500 microgram (mcg) midazolam, single oral dose on Days 1, 17, and 35; 20 mg simvastatin, single oral dose on Days 2 and 36; 250 microgram (mcg) midazolam, intravenous (IV) on Days 3 and 37; 50 mg LY3314814, single oral dose on Day 4; 50 mg LY3314814, single oral dose, Days 10 to 37
|
Cohort B
n=32 participants at risk
5 mg donepezil, single oral dose on Day 1 Period 1; 50 mg LY3314814, single oral dose Days 1 to 43, Period 2; 5 mg donepezil, single oral dose on Day 28 Period 2
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
2.0%
1/50 • Number of events 1
|
6.2%
2/32 • Number of events 2
|
|
Injury, poisoning and procedural complications
Contusion
|
2.0%
1/50 • Number of events 1
|
6.2%
2/32 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/50
|
6.2%
2/32 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/50
|
6.2%
2/32 • Number of events 2
|
|
Nervous system disorders
Headache
|
4.0%
2/50 • Number of events 2
|
6.2%
2/32 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.0%
3/50 • Number of events 3
|
0.00%
0/32
|
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