Clinical trial NCT01221519: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
High Blood Sugar
Keywords: Phase I
Bioavailability
Type 2 Diabetes Mellitus
Diabetic treatment
Metformin
High blood sugar
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-10-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 1
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 1
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 1
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 2
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 2
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 2
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 3
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 3
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 3
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 4
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 4
measure: 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.
timeFrame: Blood samples will be collected from predose to 48 hrs at each treatment period 4
Secondary outcomes:
measure: 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.
timeFrame: start of treatment until follow up
measure: 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
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 1
measure: 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).
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 1
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 1
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 1
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 1
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 2
measure: 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).
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 2
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 2
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 2
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 2
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 3
measure: 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).
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 3
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 3
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 3
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 3
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 4
measure: 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).
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 4
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 4
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 4
measure: 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.
timeFrame: PK blood samples will be collected from predose to 48 hrs after each treatment period 4
measure: 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
timeFrame: PK blood samples will be collected from predose to 48 hrs after treatment period and P-glucose on Day 1 of each treatment period
measure: 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
timeFrame: PK blood samples will be collected from predose to 48 hrs after treatment period and P-glucose on Day 1 of each treatment period
Other outcomes:
Locations:
city: St. Paul
country: United States
facility: Research Site
state: Minnesota
Study officials:
affiliation: AstraZeneca Sweden
name: Eva Johnsson, MD, PhD
role: STUDY_DIRECTOR
affiliation: Prism Research
name: Mark Matson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca R&D Mölndal
name: Mirjana Kujacic Kujacic, MD, PhD
role: STUDY_CHAIR
References: