Back to resultsA Relative Bioavailability Study Measuring the Extent and Rate of Absorption of Different Tablet Formulations of AZD1656 in Type 2 Diabetes Mellitus (T2DM) Patients
Primary Purpose
Type 2 Diabetes Mellitus, High Blood Sugar
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AZD1656
Sponsored by
About this trial
This is an interventional basic science trial for Type 2 Diabetes Mellitus focused on measuring Phase I, Bioavailability, Type 2 Diabetes Mellitus, Diabetic treatment, Metformin, High blood sugar
Eligibility 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.
Sites / Locations
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
1
2
3
Arm Description
AZD1656
AZD1656
AZD1656
Outcomes
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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).
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.
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.
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.
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.
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).
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.
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.
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.
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.
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).
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.
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.
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.
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.
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).
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.
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.
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.
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01221519
Brief Title
A Relative Bioavailability Study Measuring the Extent and Rate of Absorption of Different Tablet Formulations of AZD1656 in Type 2 Diabetes Mellitus (T2DM) Patients
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus, High Blood Sugar
Keywords
Phase I, Bioavailability, Type 2 Diabetes Mellitus, Diabetic treatment, Metformin, High blood sugar
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
AZD1656
Arm Title
2
Arm Type
Experimental
Arm Description
AZD1656
Arm Title
3
Arm Type
Experimental
Arm Description
AZD1656
Intervention Type
Drug
Intervention Name(s)
AZD1656
Intervention Description
3 different formulations, A, B and C of AZD1656 assessed before food intake and formulation B also after food intake
Primary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eva Johnsson, MD, PhD
Organizational Affiliation
AstraZeneca Sweden
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Mark Matson, MD
Organizational Affiliation
Prism Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mirjana Kujacic Kujacic, MD, PhD
Organizational Affiliation
AstraZeneca R&D Mölndal
Official's Role
Study Chair
Facility Information:
Facility Name
Research Site
City
St. Paul
State/Province
Minnesota
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Relative Bioavailability Study Measuring the Extent and Rate of Absorption of Different Tablet Formulations of AZD1656 in Type 2 Diabetes Mellitus (T2DM) Patients
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