Clinical trial NCT02714569: A Study to Evaluate LY3202328 in Overweight Healthy Participants and Dyslipidemia
Official title: A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Oral Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of LY3202328
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dyslipidemias
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-03-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Part A is a crossover. Part B is a parallel assignment.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline, Up to 42 Days
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY3202328 (LY) in Part A After a Single Dose
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 hours Postdose
measure: PK: Steady State Maximum Plasma Concentration (Cmax) of LY3202328 (LY) in Part B
timeFrame: Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose
measure: PK: Area Under the Serum Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of LY3202328 (LY) in Part A After a Single Dose
timeFrame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 hours Postdose
measure: PK: Steady State Area Under the Serum Concentration-Time Curve During the Dosing Interval (AUCτ) of LY3202328 (LY) in Part B
timeFrame: Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose
measure: PK: Time to Maximum Concentration (Tmax) of LY3202328 (LY) in Part A
timeFrame: Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96 hours Postdose
measure: PK: Steady State Tmax of LY3202328 (LY) in Part B
timeFrame: Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose
measure: Pharmacodynamics (PD): Change From Baseline in Fasting High-Density Lipoprotein Cholesterol (HDL-c) in Part A
timeFrame: Predose, 24, 48, 96 Hours Postdose
measure: PD: Change From Baseline to Last Day of Dosing in Fasting HDL-c in Part B
timeFrame: Predose, Days 7, 14, 21, and 28 Postdose
measure: PD: Change From Baseline in Fasting Total Triglycerides Part A
timeFrame: Predose, 24, 48, 96 Hours Postdose
measure: PD: Change From Baseline to Last Day of Dosing in Fasting Total Triglycerides in Part B
timeFrame: Predose, Days 7, 14, 21, and 28 Postdose
measure: PD: Change From Baseline to in Fasting Total Cholesterol in Part A
timeFrame: Predose, 24, 28, 96 Hours Postdose
measure: PD: Change From Baseline to Last Day of Dosing in Fasting Total Cholesterol in Part B
timeFrame: Predose, Days 7, 14, 21, and 28 Postdose
measure: PD: Change From Baseline in Fasting Low-Density Lipoprotein Cholesterol (LDL-c) in Part A
timeFrame: Predose, 24, 48, 96 Hours Postdose
measure: PD: Change From Baseline to Last Day of Dosing in Fasting LDL-c in Part B
timeFrame: Predose, Days 7, 14, 21, and 28 Postdose
measure: PK: Cmax of Simvastatin With/Without LY3202328 (LY) in Part B
timeFrame: Day -7 and Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose
measure: PK: Area Under Concentration Curve From Zero to Time (AUC [0-t]) of Simvastatin With/Without LY3202328 (LY) in Part B
timeFrame: Day -7 and Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose
measure: PK: Cmax of Atorvastatin With/Without LY3202328 (LY) in Part B
timeFrame: Day -7 and Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose
measure: PK: AUC (0-t) of Atorvastatin With/Without LY3202328 (LY) in Part B
timeFrame: Day -7 and Day 28: Predose, 0.5, 1, 2, 4, 4.5, 5, 6, 8, 12, 24 hours Postdose
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, Inc.
state: Florida
city: Lenexa
country: United States
facility: PRA Health Sciences
state: Kansas
city: Marlton
country: United States
facility: PRA Health Sciences
state: New Jersey
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: