Safety, Pharmacokinetics and Efficacy of Bimagrumab in Overweight and Obese Patients With Type 2 Diabetes

Novartis Pharmaceuticals78 enrolled

Overview

This study assessed the safety, pharmacokinetics and efficacy of bimagrumab when administered in overweight and obese patients with type 2 diabetes

A non-confirmatory, randomized, subject and investigator blinded, placebo controlled, parallel-arm study, investigating a 48-week treatment period with i.v. bimagrumab 10 mg/kg in overweight and obese subjects with type 2 diabetes. Participants were randomized and assigned to one of the following 2 treatment arms in a ratio of 1:1: Arm 1: Bimagrumab 10 mg/kg up to maximum 1200 mg, every 4 weeks (12 doses) until week 44. Arm 2: Placebo, every 4 weeks (12 doses) until week 44. The study consisted of a screening baseline period of 3 weeks, treatment period of 48 weeks and then a follow-up period of 8 weeks. Treatment period visits were scheduled every 4 weeks until week 44. Administration of bimagrumab or placebo was done via an i.v. infusion over 30 minutes followed by flushing for 15 minutes. Subjects were asked to return to the Investigator site for dosing approximately every 4 weeks during the treatment period. During those visits, subjects were evaluated for safety, tolerability, PK and efficacy. The treatment period ended approximately 4 weeks after the last dose administration.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Diabetes Mellitus, Type 2

Interventions

BYM338 10 mg/kgDRUG

intravenous infusion every four weeks

PlaceboOTHER

intravenous infusion every four weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Type 2 diabetes with HbA1c between 6.5% and 10% at screening with stable treatment for 3 months prior to randomization * On one of the following anti-diabetes regimens with stable treatment for approximately 3 months prior to randomization: 1) metformin monotherapy; 2) DPP4 inhibitor agent monotherapy; 3) combination therapy of metformin and DPP4 inhibitor agent; 4) no anti-diabetes therapy. * Body Mass Index of 28 to 40 kg/m2 at screening * Body weight between 65 and 140 kg at screening Exclusion Criteria: * Women of child-bearing potential unless they are using highly effective methods of contraception * Diabetes other than Type 2 such as Type 1 diabetes, surgically induced diabetes, "brittle" type 2 diabetes as per investigator judgement, history of severe hypoglycemic episodes in the year preceding screening or hypoglycemic unawareness * History of clinically significant arrythmias, heart failure, unstable angina, myocardial infarction or stroke, coronary artery bypass graft surgery, or percutaneous coronary intervention, deep vein thrombosis/pulmonary embolism, valve disorders or defects, pulmonary hypertension within 6 months of screening or 1 year for drug-eluting stents * Tachycardia * Use of anti-obesity medications, nutritional supplements or over the counter products for weight loss within 3 months of screening * Use of medications known to induce weight gain such as some anti-convulsant and psychotropic medications within 3 months of screening * Any chronic active infection (e.g., HIV, Hepatitis B or C, tuberculosis, etc) or has received anti-HCV treatments within the previous 6 months. * Uncontrolled thyroid disease. Stable euthyroid patients on stable thyroid replacement therapy for at least 3 months of screening are allowed. * Abnormal liver function tests such as SGOT, SGPT, alkaline phosphatase, or serum bilirubin, or abnormal lipase and/or amylase. * Known history or presence of severe active acute or chronic liver disease (e.g., cirrhosis). * Uncontrolled depression * Use of skeletal muscle anabolic agents in any form for 3 months prior to screening * Chronic kidney disease \[estimated glomerular filtration rate (GFR) \< 30 mL/min\];

Locations (9)

Novartis Investigative Site

Anaheim, California, United States

Novartis Investigative Site

Miami, Florida, United States

Novartis Investigative Site

Miami, Florida, United States

Novartis Investigative Site

Outcomes

Primary Outcomes

Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 48

Dual energy X-ray absorptiometry (DXA) was used to assess changes in body composition, including total fat and lean body mass (FM and LBM) and appendicular skeletal fat and muscle mass (aFM and aLBM). DXA instruments had a source that generated x-rays split into two energies which measured bone mineral mass and soft tissue from which fat and fat-free mass (or lean body mass) were estimated.

Time frame: Baseline, Week 48

Secondary Outcomes

Change From Baseline in Total Body Fat Mass by Dual Energy X-ray Absorptiometry (DXA) at Week 24

Time frame: Baseline, Week 24

Change From Baseline in HbA1c at Week 24 and 48

HbA1c reflects average glucose concentrations over the past 3 months and therefore provides a useful index of the glycemic control of bimagrumab over that time period. It is a standard endpoint used to assess the glycemic efficacy of any anti-diabetic medication. HbA1c is a key glycemic parameter which correlates with reduction of risk of diabetic complications.

Time frame: Baseline, Week 24, Week 48

The Trough Observed Analyte Concentration (Ctrough) of Repeat Doses of BYM338 10 mg/kg on Day 84, 168, 252, 308 and 336

The trough observed analyte concentration (Ctrough) is the concentration that is just prior to the beginning of, or at the end of, a dosing interval (μg/mL).

Time frame: Day 84, 252, 336 at pre-dose only. Day 168, 308 at pre-dose and 45 mins post-dose

Data from ClinicalTrials.gov

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