A Pharmacodynamic/Pharmacokinetic Study of Aleglitazar in Patients With Type 2 Diabetes Mellitus on Treatment With Lisinopril

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Investigate the Effects of Aleglitazar 150 µg in Type 2 Diabetic Patients Treated With Lisinopril 20 mg on Renal Function, the Renin-angiotensin System and the Pharmacokinetics of Lisinopril

This randomized, double-blind, placebo-controlled, parallel-group study will evaluate the effect of aleglitazar on renal function, the renin-angiotensin system and the pharmacokinetics of lisinopril in patients with type 2 diabetes mellitus treated with lisinopril. Patients on a stable dose of lisinopril (20 mg daily orally) for 2 weeks will be randomized to receive either aleglitazar (150 mcg orally daily) or placebo in addition to lisinopril for 4 weeks.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus Type 2
• Intervention / Treatment: Drug: aleglitazar; Drug: lisinopril; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
  • Nebraska
    • Omaha, Nebraska, United States, 68154
  • Texas
    • Dallas, Texas, United States, 75247
    • San Antonio, Texas, United States, 78209

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult male and female patients, 18 to 65 years of age, inclusive
• Diabetes mellitus Type 2, diagnosed at least 3 months before screening
• Treated with stable dose of metformin for at least 4 weeks prior to screening
• Treated with stable dose of Angiotensin-converting enzyme inhibitor (ACEI) for at least 4 weeks prior to screening
• Body mass index (BMI) 18 to 38 kg/m2, inclusive

Exclusion Criteria:

• Positive for HIV-1, HIV-2, hepatitis B or hepatitis C infection
• Pregnant or lactating females
• Type 1 diabetes or secondary from of diabetes
• History or evidence of proliferative diabetic retinopathy or clinically significant neuropathy
• Clinically significant hepatic disease
• Clinically significant renal impairment
• History or evidence of clinically significant cardio-vascular disease or disorder
• Acute infection or current malignancy requiring treatment except for excised basal cell carcinoma

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: aleglitazar; 150 mcg orally daily, 4 weeks (Day 15 to Day 43); Drug: lisinopril; 20 mg orally daily, 6 weeks (Day 1 to Day 43)
Placebo Comparator: 2	Drug: lisinopril; 20 mg orally daily, 6 weeks (Day 1 to Day 43); Drug: placebo; aleglitazar matching placebo orally daily, 4 weeks (Day 15 to Day 43)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Glomerular filtration rate (mGFR), measured as iohexol clearance	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Estimated glomerular filtration rate, using modification of diet in renal disease formula (eGFR[MDRD])	4 weeks
Effective renal plasma flow rate (ERPF), measured as Para-amino hippuric acid (PAH) clearance (PAH plasma concentrations)	4 weeks
Electrolyte blood/urine concentrations	4 weeks
Renin-angiotensin system: plasma renin/aldosterone levels)	4 weeks
Anti-diuretic hormone (ADH) blood levels	4 weeks
Safety: Incidence of adverse events	up to 18 weeks
Effect of multiple doses of aleglitazar on lisinopril steady-state pharmacokinetics (area under the concentration - time curve [AUC])	4 weeks
Steady-state pharmacokinetics (AUC) of aleglitazar in co-administration with lisinopril	4 weeks
High density lipoprotein-cholesterol (HDL-C) blood levels	4 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: July 19, 2011
• First Submitted That Met QC Criteria: July 19, 2011
• First Posted (Estimate): July 20, 2011

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Protective Agents; Cardiotonic Agents; Angiotensin-Converting Enzyme Inhibitors; Lisinopril
• Other Study ID Numbers: BP25328