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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus, High Blood Sugar

Intervention / Treatment
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* Drug: AZD1656


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Bioavailability, Type 2 Diabetes Mellitus, Diabetic treatment, Metformin, High blood sugar