Healthy Volunteers
Conditions
Brief summary
The aim of this two-period study is to compare how much of the study drug gets into the blood stream when it is given as a single oral dose and when it is given as a single oral dose in combination with rifampin (a Food and Drug Administration \[FDA\] approved antibiotic that is used to treat tuberculosis, a bacterial infection that mainly affects the lungs, and other infections). Each participant will complete both study periods. The study will last about 34 days. Screening is required within 28 days before study drug is given.
Interventions
DRUGLY2835219
Administered orally
DRUGRifampin
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy sterile males or surgically sterile females or postmenopausal females * Have a body mass index (BMI) of 18 to 32 kilogram per meter square (kg/m\^2)
Exclusion criteria
* Have participated in a clinical trial involving investigational product within the last 30 days * 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 * Have an abnormal blood pressure * Show evidence of human immunodeficiency virus (HIV), hepatitis B or hepatitis C * Have donated blood of more than 500 milliliters (mL) within the last month * Have used or intend to use over-the-counter or prescription medication including herbal medications within 7 days prior to dosing or during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2835219 | Period 1: Day 1- Predose,1, 2, 4, 6, 8, 10 hours, Days 2-9: 24, 48, 72, 96, 120, 144, 168, and 192 hours; Period 2: Day 7- Predose,1, 2, 4, 6, 8, 10 hours, Days 8-15: 24, 48, 72, 96, 120, 144, 168, 192 hours |
| PK: Area Under the Concentration Time Curve AUC(0-∞) of LY2835219 | Period 1: Day 1- Predose,1, 2, 4, 6, 8, 10 hours, Days 2-9: 24, 48, 72, 96, 120, 144, 168, and 192 hours; Period 2: Day 7- Predose,1, 2, 4, 6, 8, 10 hours, Days 8-15: 24, 48, 72, 96, 120, 144, 168, 192 hours |
Countries
United States
Participant flow
Pre-assignment details
This is an open-label, 2-period, fixed-sequence study
Participants by arm
| Arm | Count |
|---|---|
| LY2835219 Alone, Then Rifampin, Then LY2835219 + Rifampin Single oral dose of 200 mg LY2835219 on Day 1 in Period 1. Day 2 through Day 9 in Period 1 is washout. QD doses of 600 mg of Rifampin for 6 days (Day 1 through Day 6) in Period 2. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1 (Day 1; Day 2 to Day 9 Washout) | Adverse Event | 1 |
| Period 2 (Day 7 to Day 14) | Adverse Event | 1 |
Baseline characteristics
| Characteristic | LY2835219 Alone, Then Rifampin, Then LY2835219 + Rifampin |
|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 7.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 3 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 | 15 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 3 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 | 8 / 24 | 2 / 23 | 4 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 | 1 / 23 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2835219
Time frame: Period 1: Day 1- Predose,1, 2, 4, 6, 8, 10 hours, Days 2-9: 24, 48, 72, 96, 120, 144, 168, and 192 hours; Period 2: Day 7- Predose,1, 2, 4, 6, 8, 10 hours, Days 8-15: 24, 48, 72, 96, 120, 144, 168, 192 hours
Population: All participants who received at least 1 dose of study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 mg LY2835219 | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2835219 | 134 nanogram per milliliter (ng/ml) | Geometric Coefficient of Variation 45 |
| 200 mg LY2835219 + 600 mg Rifampin | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2835219 | 10.5 nanogram per milliliter (ng/ml) | Geometric Coefficient of Variation 58 |
90% CI: [0.0671, 0.0886]
Primary
PK: Area Under the Concentration Time Curve AUC(0-∞) of LY2835219
Time frame: Period 1: Day 1- Predose,1, 2, 4, 6, 8, 10 hours, Days 2-9: 24, 48, 72, 96, 120, 144, 168, and 192 hours; Period 2: Day 7- Predose,1, 2, 4, 6, 8, 10 hours, Days 8-15: 24, 48, 72, 96, 120, 144, 168, 192 hours
Population: All participants who received at least 1 dose of study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 200 mg LY2835219 | PK: Area Under the Concentration Time Curve AUC(0-∞) of LY2835219 | 4570 nanogram x hour per mL (ng x h/mL) | Geometric Coefficient of Variation 53 |
| 200 mg LY2835219 + 600 mg Rifampin | PK: Area Under the Concentration Time Curve AUC(0-∞) of LY2835219 | 229 nanogram x hour per mL (ng x h/mL) | Geometric Coefficient of Variation 48 |
90% CI: [0.0376, 0.0581]