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
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: 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
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 23, 2014