Clinical trial NCT02593331: Study to Evaluate Safety, Tolerability, and Pharmacokinetics of BFKB8488A in Otherwise Healthy Overweight and Obese Participants With Likely Insulin Resistance
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Insulin Resistance
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-11-01
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: From baseline up to 20 Weeks
Secondary outcomes:
measure: Serum BFKB8488A Concentration
timeFrame: 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
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research Inc.
state: California
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: