Dyslipidemias, Non-Alcoholic Fatty Liver Disease
Conditions
Brief summary
The main purpose of this study is to evaluate the safety and tolerability of LY3885125 after administration of single ascending doses in participants with dyslipidemia (part A) and multiple doses in participants with non-alcoholic fatty liver disease (part B). Blood tests will be performed to check how much LY3885125 gets into the bloodstream and how long it takes the body to eliminate it. The study will last up to approximately 49 weeks for part A and 62 weeks for part B, for a total of approximately 111 weeks.
Interventions
DRUGLY3885125
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Parts A \& B * Males, or females of not of childbearing potential, * On a stable diet for the 3 months prior to randomization and willing to continue the same stable diet during the study. Part A * Dyslipidemia with the following fasted blood levels at screening: 150 mg/dL ≤ triglycerides \<500 mg/dL, AND LDL-cholesterol ≥100 mg/dL, * Body mass index (BMI) in range of 18.5 to 45.0 kg/m2. Part B * NAFLD with liver fat content ≥8% as determined by magnetic resonance imaging proton density fat fraction (MRI-PDFF), * BMI in range of 27 to 45.0 kg/m2
Exclusion criteria
Parts A \& B * History or presence of medical illness including, but not limited to, any cardiovascular, thromboembolism or bleeding disorder, hepatic, respiratory, hematological, endocrine, immune, psychiatric, or neurological disease, convulsions, or any clinically significant laboratory abnormality that, in the judgment of the Investigator, indicate a medical problem that would preclude study participation, * Uncontrolled hypertension with a resting blood pressure ≥ 160 mmHg systolic or ≥ 100 mmHg diastolic at visit 1, * Alanine transaminase (ALT) or aspartate aminotransferase (AST) \>3.0 × ULN for the reference range, * Alkaline phosphatase (ALP) \>1.5 × ULN for the reference range, * Total bilirubin (TBL) \>1.5 × ULN for the reference range, * Taken drugs associated with hepatic steatosis (e.g., amiodarone, valproic acid, methotrexate, tamoxifen) for more than 2 weeks in the 3 months prior to screening visit, * Type 1 diabetes mellitus (T1DM) or any other type of diabetes mellitus other than T2DM, * Poorly controlled T2DM with glycated hemoglobin (HbA1c) of \>9.0%, * Treatment with GLP-1 RA and GIP/GLP-1 RA and approved or experimental agents that target PCSK9 within 9 months prior to screening visit. Part B * Evidence of other forms of chronic liver disease, * Initiated treatment with, or changed dose of, medications that may cause significant weight gain or weight loss, within 3 months prior to the screening visit, * Have a self-reported change in body weight \>5 kg (11 pounds) within 3 months prior to screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With One or More Serious Adverse Event(s) Considered by the Investigator to be Related to Study Drug Administration | Baseline up to 36 weeks (Part A) | Part A: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module |
| Part B: Number of Participants With One or More SAEs Considered by the Investigator to be Related to Study Drug Administration | Baseline up to 36 weeks (Part B) | Part B: A summary of SAEs and other non-serious AEs, regardless of causality, will be reported in the Reported Adverse Events module |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of LY3885125 | Baseline up to 36 weeks (Part A) | Part A: PK: AUC of LY3885125 |
| Part A: PK: Maximum Observed Plasma Concentration (Cmax) of LY3885125 | Baseline up to 36 weeks (Part A) | Part A: PK: Cmax of LY3885125 |
| Part A: PK: Time of Maximum Observed Concentration (Tmax) of LY3885125 | Baseline up to 36 weeks (Part A) | Part A: PK: Tmax of LY3885125 |
| Part A: Pharmacodynamics (PD): Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) | Baseline up to Day 169 (Part A) | Part A: PD: Change From Baseline in PCSK9 |
| Part A: PD: Change From Baseline in Apolipoprotein B (ApoB) | Baseline up to Day 169 (Part A) | Part A: PD: Change From Baseline in ApoB |
| Part B Only: PD: Change of Liver Fat Content From Baseline by MRI-PDFF | Baseline up to 62 weeks (Part B) | Part B Only: PD: Change of Liver Fat Content from Baseline by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) |
Countries
United States
Contacts
STUDY_DIRECTORCall 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)
Eli Lilly and Company
Participant flow
Recruitment details
The study was planned to include Part A (single-ascending-dose \[SAD\]) and Part B (multiple-ascending-dose \[MAD\]). However, the study was terminated early and did not proceed to Part B; therefore, no participants were enrolled in Part B
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 0 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 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 | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 | 0 / 8 | 0 / 9 | 0 / 10 | 0 / 10 | 0 / 0 |
| other Total, other adverse events | 1 / 6 | 3 / 4 | 7 / 8 | 6 / 9 | 4 / 10 | 5 / 10 | 0 / 0 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 | 0 / 8 | 0 / 9 | 0 / 10 | 0 / 10 | 0 / 0 |
Outcome results
None listed