A Study to Evaluate LY3202328 in Overweight Healthy Participants and Dyslipidemia

Phase 1

Completed

Conditions: Dyslipidemias

Interventions: Drug: Placebo
Drug: LY3202328
Drug: Atorvastatin
Drug: Simvastatin

Registration Number: NCT02714569

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this two-part study is to evaluate the safety and tolerability of the study drug known as LY3202328 in healthy overweight participants in Part A, and those with dyslipidemia (abnormal blood fats) in Part B.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

Inclusion Criteria

Be healthy, as determined by medical history and physical examination
Male participants must be between 18 and 70 years of age and must agree to use a reliable method of birth control during the study and 3 months following the last dose of the investigational product
Female participants must be between 40 and 70 years old, and either postmenopausal or with a hysterectomy, and not pregnant and not lactating
Be on a stable diet and exercise regimen for greater than (>) 3 months prior
Have a body mass index (BMI) of 25.0 to 35.0 (Part A) or 27.0 to 40.0 (Part B) kilograms per meter squared
Have fasting triglycerides (TG) between 150 and 499 milligrams per deciliter (mg/dL) (Part B only)
Have a fasting low-density lipoprotein cholesterol (LDL-c) between 100 and 200 mg/dL (Part B only)
Have estimated glomerular filtration rate greater than or equal to (≥) 60 milliliters per minute/1.73 meter squared with no proteinuria
Be normotensive defined as supine systolic blood pressure (BP) less than or equal to (≤) 150 millimeters of mercury (mm Hg) and diastolic BP ≤ 100 mm Hg, without the use of any antihypertensive

Exclusion Criteria

Are taking a statin, any proprotein convertase subtilisin/kexin type 9 (PCSK9) medications, or have started taking other TG lowering agents (for example, niacin, fish oils)
Are currently enrolled in a clinical trial involving an investigational product or off-label use of a drug or device, or are concurrently enrolled in any other type of medical research, or have participated in a clinical trial involving an investigational product or non-approved use of a drug within the last 30 days or within 5 half-lives
Have an abnormal electrocardiogram or corrected QT or are on antihypertensive treatment
Have any current or prior history of significant cardiovascular disease
Show evidence of hepatitis C virus (HCV), Hepatitis B or other chronic liver disease
Have an alcohol intake that exceeds 7 units per week with no more than 3 units per day, or are unwilling to stop alcohol consumption for the duration of the study (1 unit = 12 ounces or 360 mL of beer; 5 ounces or 150 mL of wine; 1.5 ounces or 45 mL of distilled spirits), or are a regular user of known drugs of abuse
Have a history of untreated endocrine illness such as diabetes mellitus
Have been on medications or supplements for weight loss within 3 months
Have a history of active neuropsychiatric disease or on pharmacological therapy for such conditions (Part B, only)
Show evidence of human immunodeficiency virus (HIV) infection
Have been on medications that are known to inhibit cytochrome P450, family 3, subfamily A (CYP3A) or P-glycoprotein (P-gp), or regularly consume grapefruit
Have donated blood of more than 500 mL within the last month
Smoke >10 cigarettes per day or are unwilling to follow smoking rules

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Part A: Placebo	Placebo	A single ascending dose of placebo orally, in 1 period while fasting, and up to one period while fed.
Part B: Placebo	Placebo	A multiple ascending dose of placebo at up to 4 dose levels, orally, once daily for 29 days, while fasting and with a single dose of 10 mg statin (atorvastatin or simvastatin) one week prior to treatment and on Day 29.
Part A: LY3202328 (LY)	LY3202328	Single ascending doses of 1 milligram (mg), 3 mg, 10 mg, 30 mg, 100 mg, 300mg, 600 mg LY3202328 orally while fasting, or 30 mg LY3202328 orally while fed in 4 periods.
Part B: LY3202328 (LY)	LY3202328	A multiple ascending dose of 5 mg, 20 mg, 100 mg, and 300 mg LY3202328 at up to 4 dose levels, orally, once daily for 29 days, while fasting and with a single dose of 10 mg statin (atorvastatin or simvastatin) one week prior to treatment and on Day 29.
Part B: LY3202328 (LY)	Atorvastatin	A multiple ascending dose of 5 mg, 20 mg, 100 mg, and 300 mg LY3202328 at up to 4 dose levels, orally, once daily for 29 days, while fasting and with a single dose of 10 mg statin (atorvastatin or simvastatin) one week prior to treatment and on Day 29.
Part B: LY3202328 (LY)	Simvastatin	A multiple ascending dose of 5 mg, 20 mg, 100 mg, and 300 mg LY3202328 at up to 4 dose levels, orally, once daily for 29 days, while fasting and with a single dose of 10 mg statin (atorvastatin or simvastatin) one week prior to treatment and on Day 29.
Part B: Placebo	Atorvastatin	A multiple ascending dose of placebo at up to 4 dose levels, orally, once daily for 29 days, while fasting and with a single dose of 10 mg statin (atorvastatin or simvastatin) one week prior to treatment and on Day 29.
Part B: Placebo	Simvastatin	A multiple ascending dose of placebo at up to 4 dose levels, orally, once daily for 29 days, while fasting and with a single dose of 10 mg statin (atorvastatin or simvastatin) one week prior to treatment and on Day 29.

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration Part A and Part B	Baseline, Up to 42 Days	Number of participants with one or more SAEs in Part A and Part B. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.

Secondary Outcome Measures

Name	Time	Method
PK: Steady State Tmax of LY3202328 (LY) in Part B	Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose	PK is the Tmax of LY3202328 at steady state in Part B.
Pharmacodynamics (PD): Change From Baseline in Fasting High-Density Lipoprotein Cholesterol (HDL-c) in Part A	Predose, 24, 48, 96 Hours Postdose	Pharmacodynamics (PD) is the change from Baseline in Fasting High-Density Lipoprotein Cholesterol (HDL-c) in Part A.
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY3202328 (LY) in Part A After a Single Dose	Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 hours Postdose	Pharmacokinetics (PK) is the maximum plasma concentration (Cmax) of LY3202328 Part A after a single dose.
PK: Steady State Maximum Plasma Concentration (Cmax) of LY3202328 (LY) in Part B	Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose	PK is the maximum plasma concentration of LY3202328 (Cmax) at steady state in Part B.
PK: Area Under the Serum Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of LY3202328 (LY) in Part A After a Single Dose	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 hours Postdose	PK is the area under the serum concentration time curve from zero to Infinity (AUC\[0-∞\]) of LY3202328 in Part A after a single dose.
PK: Steady State Area Under the Serum Concentration-Time Curve During the Dosing Interval (AUCτ) of LY3202328 (LY) in Part B	Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose	PK is the area under the serum concentration-time curve (AUCτ) of LY3202328 at steady state during the dosing interval in Part B.
PK: Time to Maximum Concentration (Tmax) of LY3202328 (LY) in Part A	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 hours Postdose	PK is the time to maximum concentration (Tmax) of LY3202328 in Part A
PD: Change From Baseline to Last Day of Dosing in Fasting HDL-c in Part B	Predose, Days 7, 14, 21, and 28 Postdose	PD is the change from baseline to last day of dosing in fasting HDL-c in Part B.
PD: Change From Baseline in Fasting Total Triglycerides Part A	Predose, 24, 48, 96 Hours Postdose	PD is the change from baseline in fasting total triglycerides in Part A.
PD: Change From Baseline to Last Day of Dosing in Fasting Total Triglycerides in Part B	Predose, Days 7, 14, 21, and 28 Postdose	PD is the change from baseline to last day of dosing in fasting total triglycerides in Part B.
PD: Change From Baseline to in Fasting Total Cholesterol in Part A	Predose, 24, 28, 96 Hours Postdose	PD is the change from baseline in fasting total cholesterol in Part A.
PD: Change From Baseline to Last Day of Dosing in Fasting Total Cholesterol in Part B	Predose, Days 7, 14, 21, and 28 Postdose	PD is the change from baseline to last day of dosing in fasting total cholesterol in Part B.
PD: Change From Baseline in Fasting Low-Density Lipoprotein Cholesterol (LDL-c) in Part A	Predose, 24, 48, 96 Hours Postdose	PD is the change from baseline in fasting low-density lipoprotein cholesterol (LDL-c) Part A.
PD: Change From Baseline to Last Day of Dosing in Fasting LDL-c in Part B	Predose, Days 7, 14, 21, and 28 Postdose	PD is the change from baseline to last day of dosing in fasting LDL-c in Part B.
PK: Cmax of Simvastatin With/Without LY3202328 (LY) in Part B	Day -7 and Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose	PK: Cmax of Simvastatin with/without LY3202328 (LY) Co-administration in Part B.
PK: Area Under Concentration Curve From Zero to Time (AUC [0-t]) of Simvastatin With/Without LY3202328 (LY) in Part B	Day -7 and Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose	PK: Area Under Concentration Curve From Zero to Time (AUC \[0-t\]) of Simvastatin with/without LY3202328 (LY) Co-administration in Part B. AUC from time 0 to time t, where t is the time of last quantifiable plasma concentration.
PK: Cmax of Atorvastatin With/Without LY3202328 (LY) in Part B	Day -7 and Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose	PK: Cmax of Atorvastatin with/without LY3202328 (LY) Co-administration in Part B.
PK: AUC (0-t) of Atorvastatin With/Without LY3202328 (LY) in Part B	Day -7 and Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose	PK: AUC (0-t) of Atorvastatin with/without LY3202328 (LY) Co-administration in Part B. AUC from time 0 to time t, where t is the time of last quantifiable plasma concentration.