A Study to Evaluate LY3202328 in Overweight Healthy Participants and Dyslipidemia

A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Oral Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of LY3202328

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.

Study Overview

• Status: Completed
• Conditions: Dyslipidemias
• Intervention / Treatment: Drug: Placebo; Drug: Simvastatin; Drug: Atorvastatin; Drug: LY3202328

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, Inc.
  • Kansas
    • Lenexa, Kansas, United States, 06219
      • PRA Health Sciences
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • PRA Health Sciences
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: LY3202328 (LY); 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.	Drug: LY3202328; Administered orally
Placebo Comparator: Part A: Placebo; A single ascending dose of placebo orally, in 1 period while fasting, and up to one period while fed.	Drug: Placebo; Administered orally
Experimental: Part B: LY3202328 (LY); 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.	Drug: Simvastatin; Administered orally; Drug: Atorvastatin; Administered orally; Drug: LY3202328; Administered orally
Placebo Comparator: Part B: 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.	Drug: Placebo; Administered orally; Drug: Simvastatin; Administered orally; Drug: Atorvastatin; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline, Up to 42 Days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of LY3202328 in Overweight Healthy Participants and in Participants With Dyslipidemia

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): February 15, 2017
• Study Completion (Actual): February 15, 2017

Study Registration Dates

• First Submitted: March 16, 2016
• First Submitted That Met QC Criteria: March 16, 2016
• First Posted (Estimate): March 21, 2016

Study Record Updates

• Last Update Posted (Actual): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Simvastatin
• Other Study ID Numbers: 16417; I8Q-MC-GSEA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO