Clinical trial NCT01448824
Conditions: Healthy Participants
Keywords: Low High-density Lipoprotein (HDL) Cholesterol (HDL-C)
Sponsor: Eli Lilly and Company
Start date: 2011-10-01; Completion date: 2012-02-01
Enrollment: 82 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a 2-part study. Part 1 is to determine the safety and tolerability in healthy participants of increasing daily doses of LY2484595 for 14 days to achieve a blood level of LY2484595 much higher than what is needed for therapy. The amount of study drug that reaches the bloodstream and the time it takes for the body to get rid of it will be determined. The effect of the study drug on factors in the blood related to cholesterol will be measured.

Part 2 is to determine how ketoconazole affects how much of the study drug, LY2484595, gets into the bloodstream and how long it takes to get rid of it. Information about any side effects that may occur will also be collected.

Detailed description:
This study is a 2-part, multiple ascending dose (MAD) and drug drug interaction (DDI) study to evaluate the safety and tolerability and the effect of cytochrome P450 (CYP) 3A inhibition by ketoconazole on the pharmacokinetics of LY2484595 in healthy participants.

In the MAD portion (Part 1) of this study, participants in 4 cohorts (Cohorts A through D) will be randomized to receive either LY2484595 (5 ascending dose levels \[100 to 1800 mg\]) or placebo. Cohorts will have staggered starts ≥7 days from the previous cohort to allow for review of safety and tolerability. The total duration of Part 1 is approximately 13 weeks including screening.

Participants in Cohort A will participate in 2 periods separated by a washout period lasting ≥14 days. During Period 1, participants will receive the starting dose of LY2484595 (100 mg) or placebo once daily (QD) for 14 consecutive days. During Period 2, participants will receive the highest dose of LY2484595 (1800 mg) or placebo QD for 14 consecutive days. Participants will complete a follow-up visit ≥14 days after the last dose of study drug.

Participants in Cohorts B, C, and D will receive LY2484595 (300, 600, and 1200 mg LY2484595, respectively) or placebo QD for 14 consecutive days followed by a follow-up visit ≥14 days after last dose of study drug.

The DDI portion of this study (Part 2) will be open label and consist of 2 periods. The total duration of Part 2 is approximately 10 weeks. LY2484595 (100 mg) will be administered on Day 1 of Period 1 and on Day 5 of Period 2. In Period 2, ketoconazole (400 mg) will be administered QD for 14 consecutive days (13 days alone \[Days 1 through 4 and 6 through 14\] + 1 day with LY2484595 \[Day 5\]). There will be a ≥14-day washout period between dosing during Period 1 and Period 2. Participants will return for a follow-up visit ≥14 days after last dose of study drug.

Arms: arm 1: Period 1: Participants will receive either 100 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14 of Period 1.

Washout period lasting ≥14 days.

Period 2: Participants will receive either 1800 mg LY2484595 tablets or placebo tablets QD by mouth on Days 1 through 14 of Period 2. arm 2: Participants will receive either 300 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14. arm 3: Participants will receive either 600 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14. arm 4: Participants will receive either 1200 milligrams (mg) LY2484595 tablets or placebo tablets once daily (QD) by mouth on Days 1 through 14. arm 5: Period 1: Participants will receive 100 milligrams (mg) LY2484595 tablet by mouth on Day 1 of Period 1.

Washout period lasting ≥14 days.

Period 2: Participants will receive 400 mg ketoconazole tablets once daily (QD) by mouth on Days 1 through 14 of Period 2. Participants will receive 100 mg LY2484595 tablet by mouth on Day 5 of Period 2.
Interventions: intervention 1: LY2484595 intervention 2: Placebo intervention 3: Ketoconazole
Intervention descriptions: intervention 1: Administered orally intervention 2: Administered orally intervention 3: Administered orally

Protocol documents: