Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Drug Naive Chinese Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Active-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination With Metformin IR as Initial Therapy Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycaemic Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02273050
• Other study ID #: D1680C00009
• Status: Completed
• Phase: Phase 3
• First received: October 22, 2014
• Last updated: August 1, 2017
• Start date: December 2014
• Est. completion date: August 2016

Study information

• Verified date: August 2017
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Multicenter, Randomized, Double-Blind, Active-Controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin in Combination with Metformin IR as Initial Therapy Compared to Saxagliptin Monotherapy and to Metformin IR Monotherapy in Subjects with Type 2 Diabetes who have Inadequate Glycaemic Control

Description:

Allocation: Randomized Endpoint Classification: Efficacy/Safety study Intervention Model: Parallel Assignment Masking: Double Blind Primary Purpose: Treatment

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1136
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Subjects with type 2 diabetes mellitus; 2. HbA1c =8% but =12%; 3.Fasting C-peptide =1.0 ng/ml; 4. Subject will be drug naïve; 5. Body mass index =40 kg/m2.

Exclusion Criteria:

1. Symptoms of poorly controlled diabetes; 2. Chronic or repeated intermittent corticosteroid treatment ; 3. Calculated creatinine clearance <60 ml/min or serum creatinine >132.6 µmol/L (>1.5 mg/dL) for men, >123.8 µmol/L (>1.4 mg/dL) for women; 4. Creatine Kinase =3x ULN; 5.Abnormal TSH value at screening will be further evaluated by free T4, subjects with an abnormal free T4 will be excluded; 6. History of administration of any antihyperglycaemic therapy for a total of 28 days or for more than three consecutive days or a total of seven non-consecutive days during the eight weeks prior to screening; 7. Current treatment with a strong CYP3A4/5 inhibitor; 8. Prior treatment with saxagliptin or any DPP-4 inhibitor; 9. Significant or history of cardiovascular disease, renal disease, psychiatric disorders, Immunocompromised individuals, hemoglobinopathies, liver disease, Pancreatitis.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Saxagliptin 5 mg
Tablet, Oral, 5 mg, Once daily in the morning
• Placebo 5 mg for Saxagliptin
Tablet, Oral, 5 mg, Once daily in the morning
• Placebo 500 mg for metformin (with titration)
Tablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration.
• Metformin 500 mg with titration
Tablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration.

Locations

Country	Name	City	State
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Chuangchun
China	Research Site	Fuzhou
China	Research Site	Guiyang
China	Research Site	Ha'er bin
China	Research Site	Hangzhou
China	Research Site	Hefei
China	Research Site	Jinan
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Shijiazhuang
China	Research Site	Siping
China	Research Site	Tianjin
China	Research Site	Wuxi
China	Research Site	Yueyang

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in HbA1c From Baseline to Week 24 Provided That it is Prior to Rescue	To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to reduction in HbA1c (%) at the end of 24 weeks of double-blinded treatment.	Baseline to Week 24 (prior to rescue)
Secondary	Glycemic Response Defined as HbA1c < 7.0% at Week 24	To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to the proportion of subjects achieving a therapeutic glycemic response defined as HbA1c < 7.0% at the end of 24 weeks of double-blinded treatment.	Week 24 (prior to rescue)
Secondary	Change From Baseline to Week 24 (Prior to Rescue) in Fasting Plasma Glucose	To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to reduction in fasting plasma glucose at the end of 24 weeks of double-blinded treatment.	Baseline to Week 24 prior to rescue
Secondary	Change From Baseline to Week 24 (Prior to Rescue) in Area Under the Curve From 0-180 Minutes for Postprandial Glucose Response to a Meal Tolerance Test	To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to change in 180-minute postprandial glucose response to a meal tolerance test at the end of 24 weeks of double-blinded treatment.	Baseline to Week 24 prior to rescue
Secondary	Glycemic Response Defined as HbA1c = 6.5% at Week 24	To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to the proportion of subjects achieving a therapeutic glycemic response defined as HbA1c = 6.5% at the end of 24 weeks of double-blinded treatment.	Week 24 (prior to rescue)
Secondary	Change From Baseline to Week 24 in 120-minute Postprandial Glucose Response to a Meal Tolerance Test	To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to change in 120-minute postprandial glucose response to a meal tolerance test at the end of 24 weeks of double-blinded treatment.	Baseline to Week 24 prior to rescue
Secondary	Patients Rescued for Failing to Achieve Pre-specified Glycemic Targets or Discontinuation for Lack of Efficacy During the 24-week Double-blind Treatment Phase	To evaluate the efficacy of the combination therapy (saxagliptin + metformin) when compared to placebo + metformin and placebo + saxagliptin with respect to the proportion of subjects requiring rescue for failing to achieve pre-specified glycemic targets or discontinuing for lack of efficacy within the 24 weeks of double-blinded treatment.	Baseline to Week 24