Healthy
Conditions
Brief summary
The purpose of this study is to learn about the effect of lanabecestat on how the body absorbs and processes dabigatran etexilate and how dabigatran etexilate affects lanabecestat when they are taken together. This study will last about 28 days and participants will be asked to take an lanabecestat tablet daily for 19 days and a dabigatran etexilate tablet on 3 occasions. Screening is required within 30 days prior to the start of the study.
Interventions
DRUGLanabecestat
Administered orally
DRUGDabigatran etexilate
Administered orally
Sponsors
Eli Lilly and Company
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
\- Overtly healthy males and females
Exclusion criteria
* Eye abnormalities or disease * History of vitiligo or any skin color disorder * Have a history psychiatric or brain disease including seizures * Have smoked within the last 3 months * Are unwilling to avoid food and drinks containing grapefruit or Seville oranges for the duration of the study * Have known allergies to dabigatran etexilate and related compounds
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK) : Maximum Concentration (Cmax) of Dabigatran | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose |
| Pharmacokinetics: Area Under The Dabigatran Pharmacokinetic (PK) Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Concentration (Cmax) of Lanabecestat | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose | — |
| Pharmacokinetics: Area Under the Lanabecestat Pharmacokinetic (PK) Concentration Versus Time Curve During One Dosing Interval (24 Hours) (AUCtau) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose | — |
| Pharmacodynamics: Area Under the Effect Versus Time Curve (AUEC) of Thrombin Time | Days 1, 16 and 20: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose | — |
| Pharmacodynamics: Ratio of Maximum Effect to Baseline Effect (ERmax) of Thrombin Time | Days 1, 16 and 20: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Overall study population | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 | Physician Decision | 0 | 1 |
| Period 2 | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 36.1 years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 25 Participants |
| Region of Enrollment United States | 60 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 60 | 8 / 60 | 2 / 58 | 4 / 58 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 | 0 / 58 | 0 / 58 |
Outcome results
Primary
Pharmacokinetics: Area Under The Dabigatran Pharmacokinetic (PK) Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Pharmacokinetics: Area Under The Dabigatran Pharmacokinetic (PK) Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity) | 1090 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 61 |
| LY3314814 and Dabigatran Etexilate Day 16 | Pharmacokinetics: Area Under The Dabigatran Pharmacokinetic (PK) Concentration Versus Time Curve From Zero to Infinity (AUC[0-infinity) | 1240 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 53 |
| LY3314814 and Dabigatran Etexilate Day 20 | 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 |
Primary
Pharmacokinetics (PK) : Maximum Concentration (Cmax) of Dabigatran
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose
Population: All participants who received at least one dose of study drug and have evaluable pharmacokinetic (PK) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Pharmacokinetics (PK) : Maximum Concentration (Cmax) of Dabigatran | 128 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 69 |
| LY3314814 and Dabigatran Etexilate Day 16 | Pharmacokinetics (PK) : Maximum Concentration (Cmax) of Dabigatran | 148 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| LY3314814 and Dabigatran Etexilate Day 20 | Pharmacokinetics (PK) : Maximum Concentration (Cmax) of Dabigatran | 138 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 46 |
Secondary
Pharmacodynamics: Area Under the Effect Versus Time Curve (AUEC) of Thrombin Time
Time frame: Days 1, 16 and 20: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose
Population: All participants who received at least one dose of study drug and had evaluable Pharmacodynamic (PD) data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Pharmacodynamics: Area Under the Effect Versus Time Curve (AUEC) of Thrombin Time | 2080 seconds*hour (s*h) | Standard Deviation 517 |
| LY3314814 and Dabigatran Etexilate Day 16 | Pharmacodynamics: Area Under the Effect Versus Time Curve (AUEC) of Thrombin Time | 2170 seconds*hour (s*h) | Standard Deviation 611 |
| LY3314814 and Dabigatran Etexilate Day 20 | Pharmacodynamics: Area Under the Effect Versus Time Curve (AUEC) of Thrombin Time | 2030 seconds*hour (s*h) | Standard Deviation 518 |
Secondary
Pharmacodynamics: Ratio of Maximum Effect to Baseline Effect (ERmax) of Thrombin Time
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
Time frame: Days 1, 16 and 20: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 36 hours postdose
Population: All participants who received at least one dose of study drug and had evaluable Pharmacodynamic (PD) data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dabigatran Etexilate | Pharmacodynamics: Ratio of Maximum Effect to Baseline Effect (ERmax) of Thrombin Time | 7.10 ratio of maximum effect |
| LY3314814 and Dabigatran Etexilate Day 16 | Pharmacodynamics: Ratio of Maximum Effect to Baseline Effect (ERmax) of Thrombin Time | 7.09 ratio of maximum effect |
| LY3314814 and Dabigatran Etexilate Day 20 | Pharmacodynamics: Ratio of Maximum Effect to Baseline Effect (ERmax) of Thrombin Time | 7.00 ratio of maximum effect |
Secondary
Pharmacokinetics: Area Under the Lanabecestat Pharmacokinetic (PK) Concentration Versus Time Curve During One Dosing Interval (24 Hours) (AUCtau)
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose
Population: All participants who received one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Pharmacokinetics: Area Under the Lanabecestat Pharmacokinetic (PK) Concentration Versus Time Curve During One Dosing Interval (24 Hours) (AUCtau) | 3360 ng*h/mL | Geometric Coefficient of Variation 25 |
| LY3314814 and Dabigatran Etexilate Day 16 | Pharmacokinetics: Area Under the Lanabecestat Pharmacokinetic (PK) Concentration Versus Time Curve During One Dosing Interval (24 Hours) (AUCtau) | 3300 ng*h/mL | Geometric Coefficient of Variation 26 |
| LY3314814 and Dabigatran Etexilate Day 20 | 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 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of Lanabecestat
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Population: All participants who received one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigatran Etexilate | Pharmacokinetics: Maximum Concentration (Cmax) of Lanabecestat | 342 ng/mL | Geometric Coefficient of Variation 23 |
| LY3314814 and Dabigatran Etexilate Day 16 | Pharmacokinetics: Maximum Concentration (Cmax) of Lanabecestat | 315 ng/mL | Geometric Coefficient of Variation 21 |
| LY3314814 and Dabigatran Etexilate Day 20 | Pharmacokinetics: Maximum Concentration (Cmax) of Lanabecestat | 331 ng/mL | Geometric Coefficient of Variation 21 |