Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01221519
First received: October 12, 2010
Last updated: January 18, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
High Blood Sugar
Drug: AZD1656
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 1 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 1 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 1 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 2 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 2 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 2 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 3 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 3 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 3 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 4 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 4 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Blood samples will be collected from predose to 48 hrs at each treatment period 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: start of treatment until follow up ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 1 ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 1 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 1 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 1 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 1 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 2 ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 2 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 2 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 2 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 2 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 3 ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 3 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 3 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 3 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 3 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 4 ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 4 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 4 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 4 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: PK blood samples will be collected from predose to 48 hrs after each treatment period 4 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: PK blood samples will be collected from predose to 48 hrs after treatment period and P-glucose on Day 1 of each treatment period ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: PK blood samples will be collected from predose to 48 hrs after treatment period and P-glucose on Day 1 of each treatment period ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: September 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01221519

Locations
United States, Minnesota
Research Site
St. Paul, Minnesota, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Eva Johnsson, MD, PhD AstraZeneca Sweden
Principal Investigator: Mark Matson, MD Prism Research
Study Chair: Mirjana Kujacic Kujacic, MD, PhD AstraZeneca R&D Mölndal
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01221519     History of Changes
Other Study ID Numbers: D1020C00033
Study First Received: October 12, 2010
Last Updated: January 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Phase I
Bioavailability
Type 2 Diabetes Mellitus
Diabetic treatment
Metformin
High blood sugar

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hyperglycemia
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on November 20, 2014