Study To Assess the Pharmacokinetics of AZD1656 During Coadministration With Simvastatin

A Randomized, Open-label, 3-way Crossover Phase I Study in Type 2 Diabetes Mellitus Patients Treated With Metformin to Evaluate the Pharmacokinetics and Pharmacodynamics of Simvastatin During Coadministration With AZD1656 and to Evaluate the Pharmacokinetics of AZD1656 During Coadministration With Simvastatin

To assess the pharmacokinetics of AZD1656 during coadministration with Simvastatin.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: AZD1656; Drug: simvastatin

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with a clinical diagnosis of T2DM for at least 1 year, treated with any metformin or metformin with one other oral anti-diabetic drug (OAD)
• Body mass index between greater than or equal to 19 and less than or equal to 42 kg/m2
• HbA1c greater than 6.5% at enrollment

Exclusion Criteria:

• Clinically significant illness or clinically relevant trauma, as judged by the Investigator, within 2 weeks before the first administration of the IP
• Significant cardiovascular event within the last 6 months prior to enrollment (eg, myocardial infarction/acute coronary syndrome, revascularisation procedure, stroke or transient ischaemic attack) or heart failure New York Heart Association (NYHA) class III-IV

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; AZD1656	Drug: AZD1656; Oral tablet, BID dose
EXPERIMENTAL: 2; Simvastatin	Drug: simvastatin; Oral tablet, single dose
EXPERIMENTAL: 3; AZD1656 + simvastatin	Drug: AZD1656; Oral tablet, BID dose; Drug: simvastatin; Oral tablet, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the effect of AZD1656 on the steady state pharmacokinetics of simvastatin (including simvastatin acid) and vice versa by assessment of AUC(0-24) and Cmax.	Frequent blood samples for PK analysis will be drawn during 24 hours post morning dose on day 4 in each treatment period (1-3)

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the effect of AZD1656 on the steady state pharmacokinetics of simvastatin and simvastatin acid and vice versa by assessment of tmax, t1/2 and CL/F (only for AZD1656)	Frequent serial blood samples will be drawn during 24 hours post morning dose on Day 4 in each treatment period (1-3)
To evaluate the steady state pharmacokinetics of the AZD1656 metabolite when AZD1656 is administered with and without simvastatin, by assessment of AUC(0-24), Cmax and tmax.	Frequent serial blood samples will be drawn during 24 hours post morning dose on Day 4 in each treatment period (1-3)
To evaluate the effect of AZD1656 on the pharmacodynamics of simvastatin by assessment of AUC(0-t) and Cmax of active 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors.	Frequent serial blood samples will be drawn during 24 hours post morning dose on Day 4 in each treatment period (1-3)
To evaluate the safety and tolerability of AZD1656 alone and in combination with simvastatin by assessments of adverse events, laboratory variables, electrocardiogram, blood pressure, pulse, results of physical examination, and weight.	At pre entry, during the study days,

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Jolene K. Berg, MD, Cetero Research, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (ACTUAL): August 1, 2010
• Study Completion (ACTUAL): August 1, 2010

Study Registration Dates

• First Submitted: March 30, 2010
• First Submitted That Met QC Criteria: March 30, 2010
• First Posted (ESTIMATE): March 31, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): November 7, 2010
• Last Update Submitted That Met QC Criteria: November 5, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Type 2 Diabetes Mellitus; Glucose lowering
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: D1020C00029