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A Drug-Drug Interaction Study of Lanabecestat (LY3314814) in Healthy Participants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02406261
Recruitment Status : Completed
First Posted : April 2, 2015
Results First Posted : March 22, 2019
Last Update Posted : November 4, 2019
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Healthy
Interventions Drug: Lanabecestat
Drug: Simvastatin
Drug: Midazolam
Drug: Donepezil
Enrollment 82
Recruitment Details It was planned that all subjects in Cohort B would be enrolled at Site 002.
Pre-assignment Details  
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description 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 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 Title: Period 1
Started 50 32
Received at Least One Dose of Study Drug 50 32
Completed 47 32
Not Completed 3 0
Reason Not Completed
Lost to Follow-up             2             0
Adverse Event             1             0
Period Title: Period 2
Started 0 [1] 32
Completed 0 29
Not Completed 0 3
Reason Not Completed
Physician Decision             0             1
Protocol Violation             0             1
Withdrawal by Subject             0             1
[1]
Cohort A participated in Period 1 only
Arm/Group Title Cohort A Cohort B Total
Hide Arm/Group Description 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 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 of all reporting groups
Overall Number of Baseline Participants 50 32 82
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 32 participants 82 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
50
 100.0%
32
 100.0%
82
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 32 participants 82 participants
Female
16
  32.0%
10
  31.3%
26
  31.7%
Male
34
  68.0%
22
  68.8%
56
  68.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 32 participants 82 participants
Hispanic or Latino
21
  42.0%
7
  21.9%
28
  34.1%
Not Hispanic or Latino
29
  58.0%
25
  78.1%
54
  65.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 32 participants 82 participants
American Indian or Alaska Native
1
   2.0%
0
   0.0%
1
   1.2%
Asian
0
   0.0%
1
   3.1%
1
   1.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
20
  40.0%
14
  43.8%
34
  41.5%
White
27
  54.0%
16
  50.0%
43
  52.4%
More than one race
2
   4.0%
1
   3.1%
3
   3.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 50 participants 32 participants 82 participants
50
 100.0%
32
 100.0%
82
 100.0%
1.Primary Outcome
Title Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814
Hide Description [Not Specified]
Time Frame Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug and had evaluable PK data.
Arm/Group Title Cohort A
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 50
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram * hour per milliliter (ng*h/mL)
3200
(21%)
2.Primary Outcome
Title PK Profile for Simvastatin: AUC(0-∞)
Hide Description [Not Specified]
Time Frame Day 2 and 36: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (Cohort A)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug and had evaluable PK data.
Arm/Group Title Cohort A
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 49
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
AUC(0-∞) Simvastatin Day 2 Number Analyzed 44 participants
15.1
(84%)
AUC(0-∞) Simvastatin Day 36 Number Analyzed 48 participants
21.2
(59%)
3.Primary Outcome
Title PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose
Hide Description [Not Specified]
Time Frame Day 1, 3, 17, 35, and 37: Predose, 0.25, 0.5, 1, 2, 3, 5, 8, and 12 hours (Cohort A)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug and had evaluable PK data.
Arm/Group Title Cohort A
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 49
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
AUC(0-∞) Oral Day 1 Number Analyzed 49 participants
6.53
(38%)
AUC(0-∞) Oral Day 17 Number Analyzed 49 participants
6.24
(42%)
AUC(0-∞) Oral Day 35 Number Analyzed 49 participants
5.59
(40%)
AUC(0-∞) IV Day 3 Number Analyzed 49 participants
11.4
(22%)
AUC(0-∞) IV Day 37 Number Analyzed 47 participants
11.6
(21%)
4.Primary Outcome
Title PK Profile for Donepezil: AUC(0-∞)
Hide Description [Not Specified]
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug and had evaluable PK data.
Arm/Group Title Cohort B
Hide Arm/Group Description:
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
Overall Number of Participants Analyzed 31
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Day 1 Number Analyzed 31 participants
271
(28%)
Day 28 Number Analyzed 29 participants
285
(23%)
5.Secondary Outcome
Title Number of Participants With One or More Serious Adverse Events(s) Considered by the Investigator to be Related to Study Drug Administration
Hide Description [Not Specified]
Time Frame Cohort A : Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug.
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 50 32
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
Hide Description 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.
Time Frame Cohort A: Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study drug.
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description:
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
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
Overall Number of Participants Analyzed 50 32
Measure Type: Count of Participants
Unit of Measure: Participants
Suicidal Ideation
0
   0.0%
0
   0.0%
Suicidal Behavior
0
   0.0%
0
   0.0%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort A Cohort B
Hide Arm/Group Description 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 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
All-Cause Mortality
Cohort A Cohort B
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Cohort A Cohort B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/50 (0.00%)      0/32 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort A Cohort B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/50 (12.00%)      7/32 (21.88%)    
Gastrointestinal disorders     
Diarrhoea † 1  1/50 (2.00%)  1 2/32 (6.25%)  2
Injury, poisoning and procedural complications     
Contusion † 1  1/50 (2.00%)  1 2/32 (6.25%)  2
Musculoskeletal and connective tissue disorders     
Back pain † 1  0/50 (0.00%)  0 2/32 (6.25%)  2
Pain in extremity † 1  0/50 (0.00%)  0 2/32 (6.25%)  2
Nervous system disorders     
Headache † 1  2/50 (4.00%)  2 2/32 (6.25%)  2
Skin and subcutaneous tissue disorders     
Pruritus † 1  3/50 (6.00%)  3 0/32 (0.00%)  0
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5079
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02406261    
Other Study ID Numbers: 16014
I8D-MC-AZER ( Other Identifier: Eli Lilly and Company )
First Submitted: March 2, 2015
First Posted: April 2, 2015
Results First Submitted: December 13, 2018
Results First Posted: March 22, 2019
Last Update Posted: November 4, 2019