Study to Assess the Safety and Tolerability After Multiple Oral Doses of AZD1656 in Patients With Type 2 Diabetes Mellitus Treated With Metformin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00817778
First received: January 5, 2009
Last updated: October 16, 2012
Last verified: October 2012
  Purpose

The purpose of this study is to assess the 1 month safety and tolerability after multiple oral doses of AZD1656 in patients with Type 2 Diabetes Mellitus Treated with Metformin


Condition Intervention Phase
Type 2 Diabetes
Drug: AZD1656
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Randomised, Single-Blind, Placebo-Controlled, Phase IIA Study to Assess the Safety and Tolerability After Multiple Oral Doses of AZD1656 in Patients With Type 2 Diabetes Mellitus Treated With Metformin

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Systolic Blood Pressure, Change From Baseline to End of Treatment [ Time Frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period ] [ Designated as safety issue: No ]
  • Diastolic Blood Pressure, Change From Baseline to End of Treatment [ Time Frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period ] [ Designated as safety issue: No ]
  • Pulse, Change From Baseline to End of Treatment [ Time Frame: Baseline is pre-dose first day of dosing, end of treatment is the morning following the treatment period ] [ Designated as safety issue: No ]
  • Weight, Change From Baseline to End of Treatment [ Time Frame: Baseline is the day before first dose, end of treatment is last day of treatment ] [ Designated as safety issue: No ]
  • Clinically Relevant Change of Laboratory Variables [ Time Frame: Measured regularly from day before first dose to day after last dose ] [ Designated as safety issue: No ]
    Number of participants with clinically relevant change of laboratory variables (clinical chemistry, haematology and urinalysis parameters


Secondary Outcome Measures:
  • Area Under the Plasma Concentration vs Time Curve (AUC0-24) of AZD1656 [ Time Frame: Measured last day of treatment ] [ Designated as safety issue: No ]
    Dose-adjusted to a total daily dose of 100 mg due to titrated doses

  • Maximum Plasma Concentration of AZD1656 [ Time Frame: Measured last day of treatment ] [ Designated as safety issue: No ]
    Dose-adjusted to a morning dose of 50 mg due to titrated doses

  • Time to Reach Maximum Plasma Concentration of AZD1656 [ Time Frame: Measured last day of treatment ] [ Designated as safety issue: No ]
  • Terminal Elimination Half-life of AZD1656 [ Time Frame: Measured following the afternoon dose last day of treatment ] [ Designated as safety issue: No ]
  • Apparent Oral Clearance of AZD1656 [ Time Frame: Measured last day of treatment ] [ Designated as safety issue: No ]
  • P-Glucose (AUC0-24)/24, Change From Baseline to End of Treatment [ Time Frame: Baseline is the day before first dose, end of treatment is last day of treatment ] [ Designated as safety issue: No ]
    Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent.

  • S-Insulin (AUC0-24)/24, Change From Baseline to End of Treatment [ Time Frame: Baseline is the day before first dose, end of treatment is last day of treatment ] [ Designated as safety issue: No ]
    Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent.

  • S-C-Peptide (AUC0-24)/24, Change From Baseline to End of Treatment [ Time Frame: Baseline is the day before first dose, end of treatment is last day of treatment ] [ Designated as safety issue: No ]
    Log ratio (End of treatment/Baseline) has been analysed in a mixed-effect ANOVA model, using treatment as fixed effect and log(Baseline) as covariate. Resulting estimates have been back-transformed from the log-scale and then multiplied by 100 to obtain the relative ratio (end of treatment/placebo) in percent.


Enrollment: 27
Study Start Date: January 2009
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD1656
Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
Drug: AZD1656
Subjects will be treated with tolerable dose twice daily for another 24 days.
Placebo Comparator: Placebo
Dose titration of oral suspension during 4 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose twice daily for another 24 days
Drug: Placebo
Subjects will be treated with tolerable dose twice daily for another 24 days.

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or women of non-childbearing potential (postmenopausal, and/or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy/ tubal ligation)
  • Ongoing treatment with metformin on a stable dose of ≥ 1500 mg/day for at least 8 weeks prior to randomisation
  • HbA1c ≤ 10% at enrolment (HbA1c value according to international Diabetes Control and Complications Trial [DCCT] standard)

Exclusion Criteria:

  • History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease
  • Clinically significant abnormalities in ECG, clinical chemistry, haematology, or urine analysis results. Positive test for Hepatitis B surface antigen or antibodies to human immunodeficiency virus (HIV) or antibodies to Hepatitis C virus
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00817778

Locations
United States, Texas
Research Site
San Antonio, Texas, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Klas Malmberg, MD, PhD, Prof AstraZeneca R&D Mölndal
Principal Investigator: Emanuel P DeNoia, M.D Healthcare Discoveries LLC Icon Development Solutions
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00817778     History of Changes
Other Study ID Numbers: D1020C00019
Study First Received: January 5, 2009
Results First Received: July 24, 2012
Last Updated: October 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Type II Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 21, 2014