Healthy
Conditions
Brief summary
The purpose of this study is to measure how much of a new tablet formulation of lanabecestat gets into the blood stream and how long it takes the body to get rid of it, compared to the current tablet formulation of lanabecestat. The effect of a high fat meal on how quickly the body absorbs the new tablet formulation will also be evaluated. In addition any side effects of the study drug using both the new and current tablet formulations will be evaluated. The study will last about 22 days, with screening required within 30 days prior to the start of the study.
Interventions
DRUGLanabecestat
Administered orally
Sponsors
Eli Lilly and Company
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
\- Male participants: Will be sterile (including vasectomy) or agree to use an effective method of birth control and will not donate sperm during the study and for 3 months following the last dose of the investigational product \- Female participants: Women not of childbearing potential due to surgical sterilization or confirmed by medical history or menopause \- Are able to eat a high-fat, high-calorie meal within the defined time limit and abide by the food restrictions throughout the study
Exclusion criteria
* Have a history of or current, significant ophthalmic disease, as determined by the investigator or ophthalmologist * Have vitiligo or any other clinically significant disorder of skin pigmentation as determined by the investigator or dermatologist * History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs * History of previous or ongoing psychiatric disease/condition * Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study, or have a history of significant dysrhythmias or atrioventricular (AV) block (including first degree AV block). Participants with history of persistent PR interval greater than (\>)200 milliseconds (msec) will be excluded * Have prolonged Fridericia-corrected QT interval (QTcF) of \>470 msec * Have a clinically significant abnormal blood pressure or heart rate (supine) as determined by the investigator * Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs * Are unwilling to comply with the dietary requirements/restrictions during the study * Evidence of active renal disease (e.g, diabetic renal disease, polycystic kidney disease) or calculated creatinine clearance \<50 milliliters per minute (mL/min)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics(PK): Maximum Concentration (Cmax) of LY3314814 (AZD3293) | Day 1 of Periods 1, 2, and 3: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 56, 72, 96, and 120 hours post-dose |
| PK: Time of Maximum Observed Drug Concentration (Tmax) of LY3314814 (AZD3293) | Day 1 of Periods 1, 2, and 3:Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 56, 72, 96, and 120 hours post-dose |
| PK: Area Under the Concentration Versus Time Curve (AUC) of LY3314814 (AZD3293) | Day 1 of Periods 1, 2, and 3: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 56, 72, 96, and 120 hours post-dose |
Participant flow
Recruitment details
To obtain representative age-related data, attempts were made to enroll at least 6 participants who were \>55 years of age.
Pre-assignment details
Participants were randomized to 1 of 6 treatment sequences over 3 treatment periods that were 7 days long with a 7-day washout period between doses. Participants were either in a fasted state or fed state. Sequences contain a Reference (Fasted) dose; Test (Fasted) dose, and Test (Fed) dose: R (Fast)/ T (Fast)/ T (Fed), respectively.
Participants by arm
| Arm | Count |
|---|---|
| 18 to 55 Years LY3314814 (AZD3293): 50 mg administered once PO in each of 3 treatment periods. Reference formulation for fasted group Test formulation for fasted and non-fasted group | 8 |
| > 55 Years LY3314814 (AZD3293): 50 mg administered once orally PO in each of 3 treatment periods. Reference formulation for fasted group Test formulation for fasted and non-fasted group | 10 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 2 | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 18 to 55 Years | Total | > 55 Years |
|---|---|---|---|
| Age, Continuous | 39.3 years STANDARD_DEVIATION 9.9 | 51.6 years STANDARD_DEVIATION 13.6 | 61.4 years STANDARD_DEVIATION 5.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 15 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 13 Participants | 9 Participants |
| Region of Enrollment United States | 8 Participants | 18 Participants | 10 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 13 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 18 | 4 / 17 | 4 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 | 0 / 18 |
Outcome results
Primary
Pharmacokinetics(PK): Maximum Concentration (Cmax) of LY3314814 (AZD3293)
Time frame: Day 1 of Periods 1, 2, and 3: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 56, 72, 96, and 120 hours post-dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| R (Fasted) | Pharmacokinetics(PK): Maximum Concentration (Cmax) of LY3314814 (AZD3293) | 18 to 55 Years | 194 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| R (Fasted) | Pharmacokinetics(PK): Maximum Concentration (Cmax) of LY3314814 (AZD3293) | > 55 Years | 208 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| T (Fasted) | Pharmacokinetics(PK): Maximum Concentration (Cmax) of LY3314814 (AZD3293) | 18 to 55 Years | 212 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| T (Fasted) | Pharmacokinetics(PK): Maximum Concentration (Cmax) of LY3314814 (AZD3293) | > 55 Years | 196 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
| T (Fed) | Pharmacokinetics(PK): Maximum Concentration (Cmax) of LY3314814 (AZD3293) | 18 to 55 Years | 164 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| T (Fed) | Pharmacokinetics(PK): Maximum Concentration (Cmax) of LY3314814 (AZD3293) | > 55 Years | 168 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
Primary
PK: Area Under the Concentration Versus Time Curve (AUC) of LY3314814 (AZD3293)
Time frame: Day 1 of Periods 1, 2, and 3: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 56, 72, 96, and 120 hours post-dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| R (Fasted) | PK: Area Under the Concentration Versus Time Curve (AUC) of LY3314814 (AZD3293) | > 55 Years | 3040 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 16 |
| R (Fasted) | PK: Area Under the Concentration Versus Time Curve (AUC) of LY3314814 (AZD3293) | 18 to 55 Years | 2920 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 12 |
| T (Fasted) | PK: Area Under the Concentration Versus Time Curve (AUC) of LY3314814 (AZD3293) | 18 to 55 Years | 2850 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 13 |
| T (Fasted) | PK: Area Under the Concentration Versus Time Curve (AUC) of LY3314814 (AZD3293) | > 55 Years | 3020 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 27 |
| T (Fed) | PK: Area Under the Concentration Versus Time Curve (AUC) of LY3314814 (AZD3293) | 18 to 55 Years | 2970 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 9 |
| T (Fed) | PK: Area Under the Concentration Versus Time Curve (AUC) of LY3314814 (AZD3293) | > 55 Years | 2820 nanogram*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 23 |
Primary
PK: Time of Maximum Observed Drug Concentration (Tmax) of LY3314814 (AZD3293)
Time frame: Day 1 of Periods 1, 2, and 3:Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 56, 72, 96, and 120 hours post-dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| R (Fasted) | PK: Time of Maximum Observed Drug Concentration (Tmax) of LY3314814 (AZD3293) | 18 to 55 Years | 2.00 Hour (h) |
| R (Fasted) | PK: Time of Maximum Observed Drug Concentration (Tmax) of LY3314814 (AZD3293) | > 55 Years | 2.26 Hour (h) |
| T (Fasted) | PK: Time of Maximum Observed Drug Concentration (Tmax) of LY3314814 (AZD3293) | 18 to 55 Years | 1.50 Hour (h) |
| T (Fasted) | PK: Time of Maximum Observed Drug Concentration (Tmax) of LY3314814 (AZD3293) | > 55 Years | 1.50 Hour (h) |
| T (Fed) | PK: Time of Maximum Observed Drug Concentration (Tmax) of LY3314814 (AZD3293) | 18 to 55 Years | 4.01 Hour (h) |
| T (Fed) | PK: Time of Maximum Observed Drug Concentration (Tmax) of LY3314814 (AZD3293) | > 55 Years | 3.50 Hour (h) |