Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin Combined With Metformin in Chinese Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control

May 4, 2017 updated by: AstraZeneca

A Multicenter, Randomized, Double-Blind, Phase 3b Trial to Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin in Combination With Metformin in Chinese Subjects in China With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Insulin Alone or on Insulin in Combination With Metformin

A Multicenter, Randomized, Double-Blind, Phase 3b Trial to Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin in Combination with Metformin in Chinese Subjects in China with Type 2 Diabetes Who Have Inadequate Glycaemic Control on Insulin Alone or on Insulin in Combination with Metformin

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study Design: Randomized, prospective, double-blind, two-arm, parallel group, multi-center trial.

Target Subject Population: Subjects aged ≥18 who have type 2 diabetes (HbA1c of ≥7.5% and ≤11.0% and FPG<270 mg/dL (15 mmol/L)) on stable baseline therapy (insulin alone or insulin combined with metformin, with insulin at doses of ≥20 and ≤150 units per day total) for at least eight weeks at the time of screening. Insulin may be long-acting, intermediate-acting, or pre-mixed. 444 patients are planned to be randomized.

Investigational Product, Dosage and Mode of administration: Active treatment will comprise Saxagliptin 5 mg tablets once daily.

Comparator, Dosage and Mode of administration: Matching placebo tablets will be used as comparator.

Duration of Treatment: The study is divided to a single blind placebo lead in period of 8 weeks and a double-blind treatment phase of 24 weeks. Patients will be rescued based on high FPG values.

Statistical Methods: The analysis of the primary endpoint of change from baseline to week 24 of treatment in HbA1c will consist of an analysis of covariance (ANCOVA) model with treatment group and metformin use at enrolment as fixed effects and baseline HbA1c value as a covariate. The analysis will be performed on the Full analysis Set (FAS) consisting of randomised subjects who received at least 1 randomised investigational product dose and had at least 1 non-missing baseline and 1 post-baseline efficacy assessment. Within the framework of the ANCOVA model, point estimates and two-sided 95% confidence intervals (CI) for the mean change within each treatment group as well as for the difference in mean change between treatment groups will be calculated.

The Per Protocol (PP) analysis set is a subset of the full analysis set and will consist of subjects who do not deviate from the terms of the protocol which may affect the study outcome significantly as specified in the pre-defined protocol deviation list prior to unblinding the study. All decisions to exclude subjects from the primary data set will be made prior to the unblinding of the study. The primary efficacy endpoint of change from baseline in HbA1c, demographics, and baseline diabetes related characteristics and all secondary efficacy endpoints are to be analyzed using the PP Data Set. The analyses of PPG AUC, 120 minute PPG, FPG and mean total daily dose of insulin will also be done on the FAS and use a similar ANCOVA model as described above. Subjects achieving a therapeutic glycaemic response (A1C <7%) will be analyzed using a Fisher's exact test and will include exact 95% confidence intervals. The FPG analyses will utilize the mean of the latest two FPG values prior to randomization as the baseline value. The endpoint for the FPG analysis will be the mean of the week 20 and week 24 FPG values. All analyses (except the analysis of mean total daily dose of insulin) will utilize only observations at visits prior to rescue or where the subject's mean total daily dose of insulin has not increased by >10% from baseline. If an observation at week 24 is missing or does not meet these criteria, the latest post-baseline value that does will be carried forward (LOCF). The analysis of mean total daily dose of insulin will utilize the latest, non-missing, post-baseline value regardless of rescue. Multiplicity for the primary and secondary endpoints will be controlled via a hierarchical testing procedure that utilizes the full alpha (0.05) for each test. The sequence of testing will be: 1. Change from baseline in HbA1c at Week 24. 2. Change from baseline in PPG AUC at Week 24.3. Change from baseline in 120 minute PPG at Week 24. 4. Proportion of subjects achieving HbA1c <7.0% at Week 24. 5. Change from baseline in FPG to the mean at Week 20 and Week 24. 6. Change from baseline in MTDDI at Week 24.

Study Type

Interventional

Enrollment (Actual)

953

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China
        • Research Site
      • Changchun, China
        • Research Site
      • Fuzhou, China
        • Research Site
      • Guangzhou, China
        • Research Site
      • Ha'er bing, China
        • Research Site
      • Hefei, China
        • Research Site
      • Nanchang, China
        • Research Site
      • Nanjing, China
        • Research Site
      • Shanghai, China
        • Research Site
      • ShiJiazhuang, China
        • Research Site
      • Shiyan, China
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provision of informed consent before participating in the study.
  2. Diagnosed with type 2 diabetes.
  3. Inadequate glycemic control (screening: HbA1c ≥7.5% and ≤11.0% and FPG<270 mg/dL (15mmol/L). At Day -4 visit, HbA1c ≥7.5% and ≤10.5%. and FPG<270 mg/dL (15mmol/L)).
  4. On a stable dose of insulin for 8 weeks or longer prior to screening.
  5. If taking metformin, subjects should have been taking the same daily dose for 8 weeks or longer prior to screening.
  6. Insulin type should be intermediate-acting or long-acting (basal) or premixed (premixed formulation may include short- or rapid-acting insulin as one component).
  7. Body mass index ≤45 kg/m^2.

Exclusion Criteria:

  1. Women of childbearing potential unable or unwilling to use acceptable birth control.
  2. Women who are pregnant or breastfeeding.
  3. Symptoms of poorly controlled diabetes. including but not limited to, marked polyuria and polydipsia with greater than 10% weight loss during the last three months prior to screening or other signs and symptoms.
  4. Significant cardiovascular history defined as: myocardial infarction, coronary angioplasty or bypass graft, valvular disease or repair, unstable clinical significant arrhythmia, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident.
  5. Congestive heart failure
  6. Chronic or repeated intermittent corticosteroid treatment (subjects receiving stable doses of replacement corticosteroid (except dexamethasone) therapy may be enrolled).
  7. History of unstable or rapidly progressing renal disease.
  8. History of alcohol or drug abuse within the previous year.
  9. Unstable major psychiatric disorders.
  10. History of hemoglobinopathies
  11. Immunocompromised status
  12. Severe liver disease.
  13. In subjects treated with insulin alone a calculated creatinine clearance <50 ml/min. In patients treated with insulin in combination with metformin a calculated creatinine clearance <60 ml/min or serum creatinine > 1.5 mg/dL in males or > 1.4mg/dL in females.
  14. Anemia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Saxagliptin 5mg
Saxagliptin 5mg, administered to subjects with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin
Drug: Saxagliptin 5mg
Saxagliptin 5mg (plus stable insulin dose), given orally once daily (24 weeks); subjects stratified by use of stable metformin dose; flexible insulin dose (as needed for rescue).
Other Names:
  • Insulin: intermediate-acting or basal or premixed ( include short- or rapid-acting insulin as one component). ≥20 unit/day, ≤150 units/day
  • Metformin: Glucophage, 500-2500mg/day
Placebo Comparator: Placebo
Placebo administered to subjects with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin
Drug: Placebo for Saxagliptin
Placebo tablets (plus stable insulin dose), given orally once daily (24 weeks); subjects stratified by use of stable metformin dose; flexible insulin dose (as needed for rescue).
Other Names:
  • Insulin: intermediate-acting or basal or premixed ( include short- or rapid-acting insulin as one component). ≥20 unit/day, ≤150 units/day
  • Metformin: Glucophage, 500-2500mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in HbA1c From Baseline to Week 24
Time Frame: Baseline to 24 weeks
Baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in Postprandial Glucose AUC From Baseline to Week 24 During a Meal Tolerance Test
Time Frame: Baseline to 24 weeks
Baseline to 24 weeks
Analysis of Change in 120-minute PPG From Baseline to Week 24 During a Meal Tolerance Test
Time Frame: Baseline to 24 weeks
Baseline to 24 weeks
Percentage of Patients Achieving a Therapeutic Glycaemic Response of HbA1c <7%
Time Frame: At Week 24
At Week 24
The Analysis of Change in Fasting Plasma Glucose From Baseline to Week 24 (This Was the Average of Weeks 20 and 24)
Time Frame: Baseline to Average of Weeks 20 and 24
Baseline to Average of Weeks 20 and 24
Analysis of Change in Mean Total Daily Dose of Insulin From Baseline to Week 24
Time Frame: Baseline to 24 weeks
Baseline to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Principal Investigator: Linong Ji, Professor, People's Hospital of Peking Universty

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 7, 2014

Primary Completion (Actual)

February 26, 2016

Study Completion (Actual)

February 26, 2016

Study Registration Dates

First Submitted

April 2, 2014

First Submitted That Met QC Criteria

April 2, 2014

First Posted (Estimate)

April 4, 2014

Study Record Updates

Last Update Posted (Actual)

October 2, 2017

Last Update Submitted That Met QC Criteria

May 4, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D1680C00010
  • 2014L00001 (Other Identifier: China: State Food and Drug Administration)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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