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

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

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.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance
• Intervention / Treatment: Other: Placebo; Drug: BFKB8488A

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Profil Institute for Clinical Research Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Participants will receive placebo matching to BFKB8488A.	Other: Placebo; Participants will receive a single dose of placebo on Day 1.
EXPERIMENTAL: BFKB8488A SC; Participants will receive single ascending SC dose of BFKB8488A in each dose escalation cohort.	Drug: BFKB8488A; Participants will receive either a single escalated dose of BFKB8488A administered SC or a single dose of BFKB8488A administered IV on Day 1.
EXPERIMENTAL: BFKB8488A IV; Participants will receive single IV dose of BFKB8488A.	Drug: BFKB8488A; Participants will receive either a single escalated dose of BFKB8488A administered SC or a single dose of BFKB8488A administered IV on Day 1.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 29, 2015
• Primary Completion (ACTUAL): March 28, 2017
• Study Completion (ACTUAL): March 28, 2017

Study Registration Dates

• First Submitted: October 20, 2015
• First Submitted That Met QC Criteria: October 30, 2015
• First Posted (ESTIMATE): November 1, 2015

Study Record Updates

• Last Update Posted (ACTUAL): May 1, 2018
• Last Update Submitted That Met QC Criteria: April 30, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Body Weight; Hyperinsulinism; Insulin Resistance; Overweight
• Other Study ID Numbers: GC29819