A Study of LY3039478 in Healthy Participants

A Single Ascending Dose Study for the Evaluation of the Effects of LY3039478 on the QT/Corrected QT Interval in Healthy Subjects and Pilot Relative Bioavailability

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02659865

Enrollment

Registered

2016-01-20

Start date

2016-01-31

Completion date

2016-06-30

Last updated

2025-08-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

The main purpose of this study is to investigate the safety of the study drug known as LY3039478 and evaluate two different formulations of LY3039478 in healthy participants. Part A has three periods. Either LY3039478 or placebo will be given once by mouth in each period. Part B has two periods. Participants will receive both formulations of LY3039478, by mouth, over the course of the study. Both parts of the study will also explore how much LY3039478 gets into the bloodstream and how long it takes the body to get rid of it. Information about any side effects will also be collected. Participants may only enroll in one part. The study will last at least 33 days, not including screening. Screening must be performed up to 30 days before enrollment. Part B was added by protocol amendment approved in April, 2016.

Interventions

DRUGPlacebo

Administered orally

DRUGLY3039478 Capsule Formulation (Formulation 3)

Administered orally

DRUGLY3039478 Drug-in Capsule (Reference, Formulation 1)

Administered orally

DRUGLY3039478 Formulated Capsule (Test, Formulation 3)

Administered orally

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

\- Body mass index (BMI) of 18 to 32 kilogram per meter square (kg/m²)

Exclusion criteria

\- Known allergies to LY3039478, related compounds or any components of the formulation * Have previously received LY3039478 * Smokers or who have stopped smoking less than 3 months prior to enrollment

Design outcomes

Primary

Measure	Time frame	Description
Pharmacokinetics (PK): Mean Time-Matched Difference in Placebo-Adjusted QTcF Interval With Time Matched Concentrations Between LY3039478 Capsule Formulation (Formulation 3) Part A	Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose	PK: mean time-matched difference in QTcF interval with time-matched concentrations between LY3039478 capsule formulation (formulation 3) compared to placebo. Analyses of QTcF was assessed by the mean change in QTcF as a function of plasma drug concentration. Triplicate measures at each time point was averaged prior to analysis. The primary analysis was based on the time-matched placebo-adjusted QTcF (ΔQTcF) for each time point, which was calculated by subtracting each participant's time-matched placebo QTcF from their QTcF results after receiving LY3039478. The relationship between plasma concentrations of LY3039478 and ΔQTcF was evaluated using a linear mixed-effects modeling approach. The response variable was ΔQTcF, and concentrations was fitted as a fixed effect with participants as a random effect. The regression slope was presented with the unit in milliseconds per nanogram per milliliter abbreviated as ms/ng/mL.

Secondary

Measure	Time frame	Description
PK: Cmax of LY3039478 Capsule Formulation (Formulation 3) Part A	Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose	PK is Cmax of LY3039478 capsule formulation (formulation 3) in part A.
PK: Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3039478 Capsule Formulation (Formulation 3) Part A	Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose	PK is the area under the concentration versus time curve from zero to infinity (AUC\[0-∞\]) of LY3039478 capsule formulation (formulation 3) in part A.
PK: Cmax of the 2 Formulations of LY3039478 Part B	Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose	PK is the Cmax of the 2 formulations of LY3039478 in part B
PK: AUC(0-∞) of the 2 Formulations of LY3039478 Part B	Predose, 0.5, 1, 2, 3, 4, 6, 8,12, 24, 36, 48 Hours Postdose	PK is the AUC(0-∞) of the 2 formulations of LY3039478 in part B.

Countries

United States

Participant flow

Pre-assignment details

Participants were randomized to 1 of 3 treatment sequences with a placebo-control in at least 1 of the 3 study periods in Part A. Each period was separated by a washout period of ≥14 days. Participants were randomized to 1 of 2 treatment sequences in Part B. Each period was separated by a washout of ≥14 days.

Participants by arm

Arm	Count
Part A Single oral dose of LY3039478 capsule formulation (formulation 3) administered in one of three periods. A washout period occurred after each period.	15
Part B Single oral dose of 50 mg drug-in capsule LY3039478 (reference, formulation 1) administered in one of two study periods. Single oral dose of 50 mg formulated capsule LY3039478 (test, formulation 3) administered in one of two study periods	14
Total	29

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Period 1	Adverse Event	0	0	0	0	1
Period 1	Withdrawal by Subject	1	0	0	0	0

Baseline characteristics

Characteristic	Part A	Part B	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	15 Participants	14 Participants	29 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	8 Participants	11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants	6 Participants	18 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	2 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	6 Participants	4 Participants	10 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	8 Participants	9 Participants	17 Participants
Region of Enrollment United States	15 Participants	14 Participants	29 Participants
Sex: Female, Male Female	2 Participants	2 Participants	4 Participants
Sex: Female, Male Male	13 Participants	12 Participants	25 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	1 / 14	1 / 10	1 / 9	0 / 10	1 / 13	1 / 14
serious Total, serious adverse events	0 / 14	0 / 10	0 / 9	0 / 10	0 / 13	0 / 14

Outcome results

Primary

Pharmacokinetics (PK): Mean Time-Matched Difference in Placebo-Adjusted QTcF Interval With Time Matched Concentrations Between LY3039478 Capsule Formulation (Formulation 3) Part A

PK: mean time-matched difference in QTcF interval with time-matched concentrations between LY3039478 capsule formulation (formulation 3) compared to placebo. Analyses of QTcF was assessed by the mean change in QTcF as a function of plasma drug concentration. Triplicate measures at each time point was averaged prior to analysis. The primary analysis was based on the time-matched placebo-adjusted QTcF (ΔQTcF) for each time point, which was calculated by subtracting each participant's time-matched placebo QTcF from their QTcF results after receiving LY3039478. The relationship between plasma concentrations of LY3039478 and ΔQTcF was evaluated using a linear mixed-effects modeling approach. The response variable was ΔQTcF, and concentrations was fitted as a fixed effect with participants as a random effect. The regression slope was presented with the unit in milliseconds per nanogram per milliliter abbreviated as ms/ng/mL.