Clinical trial NCT05407961: A Study of LY3532226 in Participants With Type 2 Diabetes Mellitus
Official title: A Phase 1b, 2-Part, Investigator- and Participant-Blind, Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LY3532226 in Participants With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2022-06-07
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY3532226 in participants with type 2 diabetes mellitus (T2DM). Blood tests will be performed to check how much LY3532226 gets into the bloodstream and how long it takes the body to eliminate it. This is a 2-part study and will last approximately 16 weeks excluding screening period for each part, respectively.


Eligibility criteria: Inclusion Criteria:

* Participants with type 2 diabetes mellitus (T2DM) for at least 3 months before screening
* Have the following glycosylated hemoglobin (HbA1c) levels at screening:

  1. HbA1c \>/= 7.0% to \</= 10.0% for participants treated with diet and exercise alone and participants treated with metformin alone, and
  2. HbA1c \>/= 6.0% to \</= 9.5% for participants treated with dipeptidyl peptidase inhibitor-4 (DPP-4) (with/without metformin) inhibitors and participants treated with metformin and sodium-glucose cotransporter-2 (SGLT-2) inhibitor
* Participants treated with diet and exercise alone or on a stable dose of metformin for at least 3 months
* Participants with body weight up to 150 kilograms (kg) and body mass index (BMI) of 23.0 to 45.0 kilograms per meter squared (kg/m²)
* Male participants who agree to use effective methods of contraception and female participants not of childbearing potential

Exclusion Criteria:

* Participants who have uncontrolled diabetes defined as an episode of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to screening
* Have a clinically significant abnormality ECG
* Have obesity induced by other endocrine disorders such as Cushing's syndrome or Prader-Willi syndrome
* Are on any glucose-lowering medications other than metformin, SGLT-2 inhibitors and/or DPP4
* Have received chronic systemic glucocorticoid therapy (\>2 weeks) in the past 6 months
* Have an average weekly alcohol intake that exceeds 21 units per week (males 65 years of age or lesser) and 14 units per week (females and males 65 years of age or older)
* Smoke more than 10 cigarettes, or cigarette equivalent, per day

Primary outcomes:
measure: Part A: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline up to Week 16
measure: Part B: Change from Baseline in Total Clamp Disposition Index (cDI)
timeFrame: Baseline up to Week 12
Secondary outcomes:
measure: Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3532226
timeFrame: Predose on Day 1 through Week 16
measure: Part A: PK: Area Under the Concentration Versus Time Curve (AUC) of LY3532226
timeFrame: Predose on Day 1 through Week 16
measure: Part B: Change from Baseline in Insulin Secretion Rate (ISR) from hyperglycaemic clamp
timeFrame: Baseline through Week 12
measure: Part B: Change from Baseline in β-cell Glucose Sensitivity (GS) from hyperglycaemic clamp
timeFrame: Baseline through Week 12
measure: Part B: Change from Baseline in Hyperinsulinemic Euglycemic Clamp M-value
timeFrame: Baseline through Week 12
measure: Part A & B: Change from Baseline in Fasting and Post meal Glucose during Standardized Mixed-meal Tolerance Test (sMMTT)
timeFrame: Baseline through Week 16
measure: Part A & B: Change from Baseline in Glycosylated Haemoglobin (HbA1c)
timeFrame: Baseline through Week 16
measure: Part A & B: Change from Baseline in Glucagon Concentration at Fasting and Post meal during sMMTT
timeFrame: Baseline through Week 16
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung
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: