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

Study Overview
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Brief Summary
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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).

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

Conditions
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Diabetes

Intervention / Treatment
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* Drug: RVX000222
* Drug: Placebo, RVX000222


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |