A Study to Evaluate LY3202328 in Overweight Healthy Participants and Dyslipidemia

Lilly

Status and phase: Completed; Phase 1

Conditions: Dyslipidemias

Treatments: Drug: LY3202328; Drug: Atorvastatin; Drug: Simvastatin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02714569

I8Q-MC-GSEA (Other Identifier)

16417

Details and patient eligibility

About

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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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60 participants in 4 patient groups, including a placebo group

Part A: LY3202328 (LY)

Experimental group

Description:

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.

Treatment:

Drug: LY3202328

Part A: Placebo

Placebo Comparator group

Description:

A single ascending dose of placebo orally, in 1 period while fasting, and up to one period while fed.

Treatment:

Drug: Placebo

Part B: LY3202328 (LY)

Experimental group

Description:

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.

Treatment:

Drug: Atorvastatin

Drug: Simvastatin

Drug: LY3202328

Part B: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Atorvastatin

Drug: Simvastatin