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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by AstraZeneca
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02104804
First received: April 2, 2014
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Saxagliptin 5mg
Drug: Placebo for Saxagliptin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • The change in glycosylated hemoglobin A1c (HbA1c) from baseline to Week 24 (prior to rescue/censoring) [ Time Frame: From baseline to week 24 (Prior to rescue/censoring) ] [ Designated as safety issue: No ]
    The primary efficacy variable is the change in HbA1c from baseline to Week 24 (prior to rescue/censoring)


Secondary Outcome Measures:
  • The change from baseline to Week 24 (prior to rescue/censoring) in the postprandial plasma glucose (PPG) area under the curve (AUC) from 0 to 180 minutes in response to a meal tolerance test [ Time Frame: From baseline to week 24 (Prior to rescue/censoring) ] [ Designated as safety issue: No ]
    Change from baseline in PPG AUC at Week 24 (prior to rescue/censoring)

  • The change from baseline to Week 24 (prior to rescue/censoring) in 120-minute postprandial plasma glucose (PPG) in response to a meal tolerance test [ Time Frame: From baseline to week 24 (Prior to rescue/censoring) ] [ Designated as safety issue: No ]
    Change from baseline in 120 minute PPG at Week 24 (prior to rescue/censoring)

  • The proportion of subjects achieving a therapeutic glycaemic response at Week 24 (prior to rescue/censoring) defined as HbA1C <7% [ Time Frame: From baseline to week 24 (Prior to rescue/censoring) ] [ Designated as safety issue: No ]
    Proportion of subjects achieving HbA1c < 7% at Week 24 (prior to rescue/censoring)

  • The change from baseline to the mean of Weeks 20 and 24 (prior to rescue/censoring) in fasting plasma glucose (FPG) [ Time Frame: From baseline to Week 20 and Week 24 (prior to rescue/censoring) ] [ Designated as safety issue: No ]
    Change in FPG from baseline to the mean of Week 20 and Week 24 (prior to rescue/censoring)

  • The change in mean total daily dose of insulin (MTDDI) from baseline to Week 24 (regardless of rescue/censoring) [ Time Frame: From baseline to week 24 (regardless of rescue/censoring) ] [ Designated as safety issue: No ]
    Change in MTDDI from baseline to Week 24


Other Outcome Measures:
  • The incidence of AE and of marked abnormalities in clinical lab tests in all subjects [ Time Frame: From screening to Week 24 ] [ Designated as safety issue: Yes ]
    The incidence of adverse events and of marked abnormalities in clinical laboratory tests in all subjects throughout the study


Estimated Enrollment: 740
Study Start Date: May 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT02104804

Contacts
Contact: Rupesh Jagadish 0086 21 6030 2724 ClinicalTrialTransparency@astrazeneca.com

Locations
China
Research Site Recruiting
Beijing, China
Research Site Recruiting
Fuzhou, China
Research Site Recruiting
Guangzhou, China
Research Site Withdrawn
Ha'er bin, China
Research Site Recruiting
Ha'er bing, China
Research Site Recruiting
Hefei, China
Research Site Recruiting
Nanchang, China
Research Site Recruiting
Nanjing, China
Research Site Recruiting
Shanghai, China
Research Site Not yet recruiting
Shanghai, China
Research Site Recruiting
ShiJiazhuang, China
Research Site Recruiting
Shiyan, China
Research Site Withdrawn
Wen Zhou, China
Research Site Withdrawn
Wuhan, China
Sponsors and Collaborators
AstraZeneca
Bristol-Myers Squibb
Investigators
Principal Investigator: Linong Ji, Professor People's Hospital of Peking Universty
  More Information

Publications:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02104804     History of Changes
Other Study ID Numbers: D1680C00010, 2014L00001
Study First Received: April 2, 2014
Last Updated: August 11, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by AstraZeneca:
Type 2 Diabetes Mellitus, Insulin, Dipeptidyl-Peptidase 4 Inhibitors, Metformin,saxagliptin,Endocrine System Diseases

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Saxagliptin
Insulin
Metformin
Insulin, Short-Acting
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014