ORION: Effects of Cenicriviroc on Insulin Sensitivity in Subjects With Prediabetes or Type 2 Diabetes Mellitus (T2DM) and Suspected NAFLD

Tobira Therapeutics

Status and phase

Completed

Phase 2

Conditions

Prediabetic State

Type 2 Diabetes Mellitus

Non-alcoholic Fatty Liver Disease

Treatments

Drug: Placebo

Drug: Cenicriviroc 150 mg

Study type

Interventional

Funder types

Industry

Identifiers

NCT02330549

652-2-204

Details and patient eligibility

About

A Phase 2a, randomized, double-blind, placebo-controlled, multi-center study of cenicriviroc (CVC) to be conducted in approximately 50 adult obese subjects [body mass index (BMI) ≥ 30 kg/m^2] with prediabetes or type 2 diabetes mellitus and suspected NALFD.

Full description

Approximately 50 adult obese subjects (BMI ≥ 30 kg/m2) with prediabetes or type 2 diabetes mellitus and suspected NALFD will be randomized into the study.

Eligible subjects will receive either CVC (n=25) or matching placebo (n=25), once daily (QD) for 24 weeks, followed by a safety follow-up visit 4 weeks after last intake of study medication.

Enrollment

45 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adult male and female subjects aged between 18-75 years
Obesity as defined by BMI ≥ 30 kg/m2
Evidence of prediabetes or type 2 diabetes mellitus based on Screening laboratory values with at least one of the following criteria:
Fasting plasma glucose (FPG) of 100 - 270 mg/dL (5.6 - 15.0 mmol/L)
Hemoglobin A1c (HbA1c) of 5.7 - 10.0%
Participants receiving metformin alone or in combination with a sulfonylurea (glimepiride, glipizide, glyburide, or gliclazide) must be on stable therapy for at least 90 days prior to Screening.
Suspected diagnosis of NAFLD warranting confirmation by liver biopsy
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 upper limit normal (ULN)
Ability to understand and sign a written informed consent form
Females of child-bearing potential and males participating in the study must agree to use at least 2 approved barrier methods of contraception throughout the duration of the study and for 3 months after stopping study drug. Females who are postmenopausal must have documentation of cessation of menses for ≥ 12 months and serum follicle stimulating hormone (FSH) ≥ 30 mU/mL
Participants receiving allowed concomitant medications need to be on stable therapy for 28 days prior to Baseline.

Exclusion criteria

Use of oral antihyperglycemic agents (OHAs) other than metformin or sulfonylureas, including but not limited to thiazolidinediones, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, meglitinides, α-glucosidase inhibitors, colesevelam, bromocriptine, pramlintide or basal insulin within 90 days prior to Screening or anticipated use during the trial
Type 1 diabetes
Hepatitis B Surface Antigen (HBsAg) positive
Human Immunodeficiency Virus-1 (HIV-1) or Human Immunodeficiency Virsu-2 (HIV-2) infection
Hepatitis C Virus Antibody (HCVAb) positive
Prior or planned liver transplantation
Other known causes of chronic liver disease, including alcoholic liver disease
History of cirrhosis and/or hepatic decompensation including ascites, encephalopathy or variceal bleeding
Alcohol consumption greater than 14 units/week
Weight reduction through bariatric surgery or planned bariatric surgery during the conduct of the study (including gastric banding)
Any Grade ≥ 3 laboratory abnormality as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Toxicity Grading Scale, except subjects with Grade ≥ 3 dyslipidemia with triglyceride or cholesterol elevations unless clinical assessment foresees an immediate health risk to the subject
Serum albumin < 3.5 g/dL
Serum creatinine levels ≥ 1.5 mg/dL for males or ≥ 1.4 mg/dL for females if participant is receiving metformin
Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) equation
Platelet count < 100,000/mm3
Hemoglobin < 12 g/dL for males or < 11 g/dL for females
Females who are pregnant or breastfeeding
Receiving ongoing therapy with any disallowed medication at Screening
Allergy to the study drug or its components
Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements.