Study to Evaluate Safety, Tolerability, and Pharmacokinetics of BFKB8488A in Otherwise Healthy Overweight and Obese Participants With Likely Insulin Resistance

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability profile of BFKB8488A following subcutaneous (SC) administration in overweight and obese participants (body mass index [BMI] greater than [>] 27 to less than or equal to [</=] 40 kilograms per square meter [kg/m^2]) with markers of insulin resistance. Single ascending fixed doses of BFKB8488A will be evaluated. Participants will be randomized into 7 sequential ascending fixed-dose cohorts of BFKB8488A SC or placebo and safety reviews will be performed before escalation to higher dose cohorts. Additionally, following the ascending fixed-dose SC cohorts, a separate cohort will open to evaluate the PK of BFKB8488A after intravenous (IV) administration.

Official Title
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A Phase Ia, Randomized, Blinded, Placebo-Controlled, Ascending Single Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Subcutaneous and Intravenous BFKB8488A in Otherwise Healthy Overweight and Obese Volunteers With Likely Insulin Resistance

Conditions
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Insulin Resistance

Intervention / Treatment
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* Drug: BFKB8488A
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with BMI >/=30 kg/m^2 and </=40 kg/m^2 or BMI >27 kg/m^2 and <30 kg/m^2 and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) >3.60 or waist circumference >100 centimeters (cm) (males) or 88 cm (females) or fasting plasma insulin >/=15 milli international unit per liter (mIU/L) or fasting plasma glucose >/=100 milligrams per deciliter (mg/dL) and <126 mg/dL or hemoglobin A1c (HbA1c) >5.6 percent (%) and <6.5% Negative pregnancy test Exclusion Criteria: A diagnosis of Type 2 diabetes mellitus at any time Pregnant, lactating or intending to become pregnant during the study or within 3 months after the study dose is administered Uncontrolled intercurrent illness or any psychiatric illness Participants actively involved in a weight loss or dietary program within the last 6 months History of surgical procedures for weight loss History of eating disorder Uncontrolled hypertension (systolic >/=140 millimeter of mercury [mmHg] or diastolic blood pressure >/=90 mmHg) either on or off therapy at screening or Day -2 Fasting triglycerides >500 mg/dL (5.64 millimoles per liter [mmol/L]) or low density lipoprotein (LDL) >160 mg/dL (4.14 mmol/L) at screening Any serious medical condition or abnormality in clinical laboratory tests

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive placebo matching to BFKB8488A. | Other: Placebo<br>* Participants will receive a single dose of placebo on Day 1.<br>|
| Experimental: BFKB8488A SC<br>Participants will receive single ascending SC dose of BFKB8488A in each dose escalation cohort. | Drug: BFKB8488A<br>* Participants will receive either a single escalated dose of BFKB8488A administered SC or a single dose of BFKB8488A administered IV on Day 1.<br>|
| Experimental: BFKB8488A IV<br>Participants will receive single IV dose of BFKB8488A. | Drug: BFKB8488A<br>* Participants will receive either a single escalated dose of BFKB8488A administered SC or a single dose of BFKB8488A administered IV on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events |  | From baseline up to 20 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum BFKB8488A Concentration |  | SC Cohort: predose (Hour 0), 4, 24, 72 hours post Day 1 dose, Days 6, 8, 11, 15, 22, 29, 36, 43, 57, 85, 113; IV Cohort: end of infusion on Day 1, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72 hours post Day 1 dose, Days 6, 8, 15, 22, 29, 36, 43 |