A Relative Bioavailability Study Measuring the Extent and Rate of Absorption of Different Tablet Formulations of AZD1656 in Type 2 Diabetes Mellitus (T2DM) Patients

Randomized, Open, 4-way Crossover, Single Center, Phase I Relative Bioavailability Study in Type 2 Diabetes Mellitus Patients to Measure the Extent and Rate of Absorption of AZD1656 From Different Tablet Formulations

The purpose of this study is to assess the relative bioavailability by measuring the extent and rate of absorption of different tablet formulations of AZD1656 in T2DM patients.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; High Blood Sugar
• Intervention / Treatment: Drug: AZD1656

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • St. Paul, Minnesota, 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:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Males or females of non-childbearing potential (post-menopausal, and/or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy/ tubal ligation) aged ≥18 years. Females will be defined as post-menopausal if last menstruation period was >1 year ago and serum follicle stimulating hormone (FSH) is within the post-menopausal range, or if age >50 years and with last menstruation period >2 years ago.
• A confirmed clinical diagnosis of T2DM for at least 1 year, treated with metformin as a single treatment or in combination with one other oral anti-diabetic (ie, DPPIV inhibitor or SU) for at least 2 months prior to screening. Doses of anti-diabetic treatment should have been stable for at least 1 month prior to screening.
• Treatment with at least 1000mg of Metformin for 2 months and being stable on the Metformin Therapy for 1 month
• Hb A1c >6.5% (international standard) at enrolment.
• Body mass index (BMI) between ≥19 and ≤42 kg/m2.

Exclusion Criteria:

• Clinically significant illness or clinically relevant trauma, as judged by the Investigator, within 2 weeks prior to the first administration of AZD1656
• Participation in another clinical study during the 30 days prior to screening or intake of another investigational drug within 30 days (or at least 5 x t1/2 of the drug) prior to the first administration of AZD1656.
• History of, or ongoing, ischemic heart disease or heart failure. Stroke, transitory ischemic attack, or symptomatic peripheral arterial disease within the last 6 months.
• Clinically significant abnormalities in ECG, clinical chemistry, hematology or urinalysis results.
• Positive test for Hepatitis B surface antigen (HBsAg) or antibodies to human immunodeficiency virus (HIV) or Hepatitis C virus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; AZD1656	Drug: AZD1656; 3 different formulations, A, B and C of AZD1656 assessed before food intake and formulation B also after food intake
Experimental: 2; AZD1656	Drug: AZD1656; 3 different formulations, A, B and C of AZD1656 assessed before food intake and formulation B also after food intake
Experimental: 3; AZD1656	Drug: AZD1656; 3 different formulations, A, B and C of AZD1656 assessed before food intake and formulation B also after food intake

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of AUC of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 1
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of Cmax of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 1
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of tmax of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 1
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of AUC of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 2
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of Cmax of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 2
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of tmax of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 2
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of AUC of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 3
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of Cmax of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 3
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of tmax of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 3
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of AUC of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 4
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of Cmax of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 4
Measure: rate and extent of absorption of AZD1656 following single-dose administration of Tablets A, B, and C, administered before food intake and following administration of Tablet B after food intake, by assessment of tmax of AZD1656.	Blood samples will be collected from predose to 48 hrs at each treatment period 4

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety of AZD1656 by assessing a panel of adverse events measures: physical examination, electrocardiogram, pulse and blood pressure, weight and laboratory, variables including plasma glucose.	start of treatment until follow up
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of AUC	PK blood samples will be collected from predose to 48 hrs after each treatment period 1
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of AUC(0-t).	PK blood samples will be collected from predose to 48 hrs after each treatment period 1
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of Cmax.	PK blood samples will be collected from predose to 48 hrs after each treatment period 1
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of tmax.	PK blood samples will be collected from predose to 48 hrs after each treatment period 1
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of t½.	PK blood samples will be collected from predose to 48 hrs after each treatment period 1
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of AUC.	PK blood samples will be collected from predose to 48 hrs after each treatment period 2
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of AUC(0-t).	PK blood samples will be collected from predose to 48 hrs after each treatment period 2
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of Cmax.	PK blood samples will be collected from predose to 48 hrs after each treatment period 2
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of tmax.	PK blood samples will be collected from predose to 48 hrs after each treatment period 2
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of t½.	PK blood samples will be collected from predose to 48 hrs after each treatment period 2
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of AUC.	PK blood samples will be collected from predose to 48 hrs after each treatment period 3
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of AUC(0-t).	PK blood samples will be collected from predose to 48 hrs after each treatment period 3
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of Cmax.	PK blood samples will be collected from predose to 48 hrs after each treatment period 3
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of tmax.	PK blood samples will be collected from predose to 48 hrs after each treatment period 3
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of t½.	PK blood samples will be collected from predose to 48 hrs after each treatment period 3
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of AUC.	PK blood samples will be collected from predose to 48 hrs after each treatment period 4
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of AUC(0-t).	PK blood samples will be collected from predose to 48 hrs after each treatment period 4
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of Cmax.	PK blood samples will be collected from predose to 48 hrs after each treatment period 4
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of tmax.	PK blood samples will be collected from predose to 48 hrs after each treatment period 4
Evaluate: pharmacokinetics of the AZD1656 metabolite, following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of t½.	PK blood samples will be collected from predose to 48 hrs after each treatment period 4
pharmacodynamics of AZD1656 following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of AUC(0-4) and AUC(0-24) for glucose	PK blood samples will be collected from predose to 48 hrs after treatment period and P-glucose on Day 1 of each treatment period
pharmacodynamics of AZD1656 following single-dose administration of Tablets A, B, and C, given before food intake and following administration of Tablet B after food intake, by assessment of AUC(0-4) for insulin	PK blood samples will be collected from predose to 48 hrs after treatment period and P-glucose on Day 1 of each treatment period

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Eva Johnsson, MD, PhD, AstraZeneca Sweden; Study Chair: Mirjana Kujacic Kujacic, MD, PhD, AstraZeneca R&D Mölndal

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: October 12, 2010
• First Submitted That Met QC Criteria: October 14, 2010
• First Posted (Estimate): October 15, 2010

Study Record Updates

• Last Update Posted (Estimate): January 19, 2012
• Last Update Submitted That Met QC Criteria: January 18, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Metformin; Bioavailability; Phase I; Type 2 Diabetes Mellitus; High blood sugar; Diabetic treatment
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: D1020C00033