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ORION: Effects of Cenicriviroc on Insulin Sensitivity in Subjects With Prediabetes or T2DM and Suspected NAFLD

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Tobira Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02330549
First received: December 22, 2014
Last updated: May 3, 2016
Last verified: May 2016
  Purpose
A Phase 2a, randomized, double-blind, placebo-controlled, multi-center study of CVC to be conducted in approximately 50 adult obese subjects (BMI ≥ 30 kg/m2) with prediabetes or type 2 diabetes mellitus and suspected NALFD.

Condition Intervention Phase
Prediabetic State
Non-alcoholic Fatty Liver Disease
Type 2 Diabetes Mellitus
Drug: Cenicriviroc 150 mg
Drug: Matching placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: ORION - Effect of CCR2 and CCR5 Antagonism by Cenicriviroc on Peripheral and Adipose Tissue Insulin Sensitivity in Adult Obese Subjects With Prediabetes or Type 2 Diabetes Mellitus and Suspected Non-Alcoholic Fatty Liver Disease (NAFLD)

Resource links provided by NLM:


Further study details as provided by Tobira Therapeutics, Inc.:

Primary Outcome Measures:
  • Changes in Insulin Sensitivity Measured by Peripheral and Adipose Tissue [ Time Frame: 24 weeks ]
    Changes in insulin sensitivity measured by peripheral and adipose tissue over 24 weeks


Secondary Outcome Measures:
  • Degree of Macrophage Infiltration in Subcutaneous Adipose Tissue [ Time Frame: 24 weeks ]
    Evaluate degree of macrophage infiltration in subcutaneous adipose tissue over 24 weeks of treatment

  • Expression of Chemokine Receptors Types 2 (CCR2) and 5 (CCR5) in Subcutaneous Adipose Tissue [ Time Frame: 24 weeks ]
    Evaluate expression of chemokine receptors types 2 (CCR2) and 5 (CCR5) in subcutaneous adipose tissue

  • Changes from Baseline in Peripheral Monocyte Subsets (CD14/CD16) [ Time Frame: 24 weeks ]
    Evaluate changes from baseline in peripheral monocyte subsets (CD14/CD16)

  • Changes in Non-invasive Imaging by Multiparametric Magnetic Resonance Imaging (MRI) for Liver Disease (LiverMultiScan™) [ Time Frame: 24 weeks ]
    Evaluate changes in non-invasive imaging by multiparametric magnetic resonance imaging (MRI) for liver disease (LiverMultiScan™)

  • Correlation of Non-invasive Liver Imaging Findings with Histology Results [ Time Frame: 24 weeks ]
    Evaluate correlation of non-invasive liver imaging findings with histology results

  • Changes from Baseline in Liver Transaminases [ Time Frame: 24 weeks ]
    Evaluate changes from baseline in liver transaminases

  • Changes from Baseline in Serum Biomarker Panel [ Time Frame: 24 weeks ]
    Evaluate changes from baseline in serum biomarker panel

  • Changes from Baseline in Metabolic Parameters [ Time Frame: 24 weeks ]
    Evaluate changes from baseline in metabolic parameters

  • Number and Percentage of Subjects with Adverse Events over 24 Weeks [ Time Frame: 24 weeks ]
    Evaluation of adverse events over 24 weeks of treatment

  • Changes from Baseline in Physical Examination over 24 Weeks [ Time Frame: 24 weeks ]
    Evaluation of physical examination

  • Changes from Baseline in Vital Signs over 24 Weeks [ Time Frame: 24 weeks ]
    Evaluation of vital signs

  • Changes from Baseline in 12 Lead ECG over 24 weeks [ Time Frame: 24 weeks ]
    Evaluation of 12 lead ECG

  • Pharmacokinetics (PK) of CVC in a population PK analysis [ Time Frame: 24 weeks ]
    Evaluate PK of CVC


Enrollment: 45
Study Start Date: June 2015
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cenicriviroc 150mg
CVC 150 mg, administered orally once daily and taken every morning with food for 24 weeks
Drug: Cenicriviroc 150 mg
CVC 150 mg, administered orally once daily and taken every morning with food
Other Name: CVC 150 mg
Placebo Comparator: Matching placeo
Matching placebo, administered orally once daily and taken every morning with food for 24 weeks
Drug: Matching placebo
Matching placebo administered orally once daily and taken every morning with food

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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%
  • Subjects 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
  • AST and ALT ≤ 5 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
  • Subjects receiving allowed concomitant medications need to be on stable therapy for 28 days prior to Baseline

Exclusion Criteria:

  • Use of 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
  • HBsAg positive
  • HIV-1 or HIV-2 infection
  • 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 subject 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02330549

Locations
United States, Texas
San Antonio, Texas, United States
Puerto Rico
San Juan, Puerto Rico
Sponsors and Collaborators
Tobira Therapeutics, Inc.
Investigators
Study Director: Eric Lefebvre, MD Tobira Therapeutics, Inc.
  More Information

Responsible Party: Tobira Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02330549     History of Changes
Other Study ID Numbers: 652-2-204
Study First Received: December 22, 2014
Last Updated: May 3, 2016

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Liver Diseases
Fatty Liver
Insulin Resistance
Non-alcoholic Fatty Liver Disease
Prediabetic State
Glucose Intolerance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Hyperinsulinism
Hyperglycemia
TAK-652
Insulin
CCR5 Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 25, 2017