The Effects of RVX000222 on Glucose Metabolism in Individuals With Pre-diabetes

Phase 2 Randomised, Double-blind, Placebo-controlled, Cross-over Study for the Assessment of Glucose Metabolism Changes With RVX000222 in Individuals With Pre-diabetes

This study builds on data that high-density lipoprotein (HDL) has a number of potentially beneficial effects including directly modulating glucose metabolism through multiple mechanisms. The primary objective of this study is to determine the effects of RVX000222 on postprandial plasma glucose in male individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), during a frequently sampled oral glucose tolerance test (OGTT).

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: RVX000222; Drug: Placebo, RVX000222

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Baker IDI Heart and Diabetes Institute 75 Commercial Road,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Males aged 18-70 years, inclusive
• Body mass index (BMI): 25-40 kg/m2
• HDL cholesterol plasma levels: ≤1.4 mmol/L
• Pre-diabetes: Either impaired fasting glucose (IFG; 6.1-6.9mmol/L) or impaired glucose tolerance (IGT; 2 hour OGTT glucose 7.8-11.0mmol/L, WHO classification) as measured at Visit 1
• No current use or need for prescription or over-the-counter medication within four days of Visit 1
• Have given signed informed consent to participate in the study

Exclusion Criteria:

• Identification of any other medical condition requiring immediate therapeutic intervention
• Has received any over-the-counter medication including vitamins, herbal, or dietary supplements within four days of Visit 1 unless prior approval from the Investigator
• Tobacco use within six months of Visit 1 (including cigarettes, pipes, chewing tobacco)
• Elective surgery requiring general anaesthesia during the course of the study
• Clinically significant heart disease at Visit 1
• Clinically significant abnormal ECG at Visit 1
• Evidence of renal impairment defined as serum creatinine >1.5 mg/dL (133 μmol/L) or creatinine clearance of <60 mL/min
• History of hypertension or supine SBP >160mmHg or DBP >95mmHg as measured at Visit 1
• Evidence of type 2 diabetes (fasting plasma glucose ≥7.0mmol/L; 2 hour OGTT glucose ≥11.1mmol/L)
• Evidence of liver disease defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT) or total bilirubin >1.5 x upper limit of normal (ULN) at Visit 1
• History of malignancy within past 5 years
• History or evidence of drug or alcohol abuse within 12 months of Visit 1
• Use of other investigational drugs and/or devices at the time of enrolment, or within 30 days of Visit 1
• History of non-compliance to medical regimens or unwillingness to comply with the study protocol
• Any condition that in the opinion of the Investigators would confound the evaluation and interpretation of the data
• Persons directly involved in the execution of the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo, RVX000222; capsule, administer with food, twice daily 10-12 hrs apart, 31-35 days; Other Names: Placebo
Experimental: RVX000222, 200 mg daily	Drug: RVX000222; capsule, 200 mg, administer with food, 100 mg twice daily 10-12 hrs apart, 31-35 days; Other Names: RVX-208

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma glucose following treatment with RVX000222 compared to placebo	The change in postprandial plasma glucose, defined as area under the glucose curve (AUGC) during a frequently sampled OGTT following RVX000222 treatment for 29-33 days as compared to placebo.	29-33 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in insulin secretion and insulin sensitivity following treatment with RVX000222 compared to placebo	The change in indices of insulin secretion (β-cell function) and insulin sensitivity during a frequently sampled OGTT following RVX000222 treatment for 29-33 days as compared to placebo.	29-33 days

Collaborators and Investigators

• Sponsor: Resverlogix Corp
• Collaborators: Nucleus Network Ltd; Baker Heart and Diabetes Institute
• Investigators: Principal Investigator: Professor Bronwyn Kingwell, Baker Heart and Diabetes Institute; Principal Investigator: Dr. Stephen Duffy, Baker Heart and Diabetes Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: November 13, 2012
• First Submitted That Met QC Criteria: November 13, 2012
• First Posted (Estimate): November 19, 2012

Study Record Updates

• Last Update Posted (Estimate): April 2, 2014
• Last Update Submitted That Met QC Criteria: March 31, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Prediabetic State
• Other Study ID Numbers: RVX222-CS-010; Alfred Study No. 409/12 (Other Identifier: Baker IDI Heart and Diabetes Institute)