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

NCT02273050 | Completed Phase 3 Results

• 1 other identifier: D1680C00009
• Study Type: interventional
• Target: 1,136
• Locations: 1 country
• Sites: 17

Brief 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

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus, Dipeptidyl-Peptidase 4 Inhibitors, Saxagliptin, Metformin, Endocrine System Diseases

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Glycemic Response Defined as HbA1c < 7.0% at Week 24

  Week 24 (prior to rescue)

• Change From Baseline to Week 24 (Prior to Rescue) in Fasting Plasma Glucose

  Baseline to Week 24 prior to rescue

• 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

  Baseline to Week 24 prior to rescue

• Glycemic Response Defined as HbA1c ≤ 6.5% at Week 24

  Week 24 (prior to rescue)

• Change From Baseline to Week 24 in 120-minute Postprandial Glucose Response to a Meal Tolerance Test

  Baseline to Week 24 prior to rescue

Study Arms (3)

Saxagliptin 5 mg + Metformin (500 mg with titration)

EXPERIMENTAL

Saxagliptin 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.

Drug: Saxagliptin 5 mg; Drug: Metformin 500 mg with titration

Saxagliptin 5 mg + Placebo

ACTIVE COMPARATOR

Saxagliptin 5 mg once daily and Placebo 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.

Drug: Saxagliptin 5 mg; Drug: Placebo 500 mg for metformin (with titration)

Metformin (500 mg with titration) + Placebo

ACTIVE COMPARATOR

Placebo 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.

Drug: Placebo 5 mg for Saxagliptin; Drug: Metformin 500 mg with titration

Interventions

Saxagliptin 5 mg DRUG

Tablet, Oral, 5 mg, Once daily in the morning

Also known as: Onglyza, BMS-477118

Saxagliptin 5 mg + Metformin (500 mg with titration); Saxagliptin 5 mg + Placebo

Placebo 5 mg for Saxagliptin DRUG

Tablet, Oral, 5 mg, Once daily in the morning

Metformin (500 mg with titration) + Placebo

Placebo 500 mg for metformin (with titration) DRUG

Tablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration.

Saxagliptin 5 mg + Placebo

Metformin 500 mg with titration DRUG

Tablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration.

Also known as: Glucophage

Metformin (500 mg with titration) + Placebo; Saxagliptin 5 mg + Metformin (500 mg with titration)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (17)

Research Site

Beijing, China

Location

Research Site

Changchun, China

Location

Research Site

Chuangchun, China

Location

Research Site

Fuzhou, China

Location

Research Site

Guiyang, China

Location

Research Site

Hangzhou, China

Location

Research Site

Ha’erbin, China

Location

Research Site

Hefei, China

Location

Research Site

Jinan, China

Location

Research Site

Nanchang, China

Location

Research Site

Nanjing, China

Location

Research Site

Shanghai, China

Location

Research Site

Shijiazhuang, China

Location

Research Site

Siping, China

Location

Research Site

Tianjin, China

Location

Research Site

Wuxi, China

Location

Research Site

Yueyang, China

Location

Related Publications (1)

• Dou J, Ma J, Liu J, Wang C, Johnsson E, Yao H, Zhao J, Pan C. Efficacy and safety of saxagliptin in combination with metformin as initial therapy in Chinese patients with type 2 diabetes: Results from the START study, a multicentre, randomized, double-blind, active-controlled, phase 3 trial. Diabetes Obes Metab. 2018 Mar;20(3):590-598. doi: 10.1111/dom.13117. Epub 2017 Oct 26.

  PMID: 28926170 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Endocrine System Diseases

Interventions

saxagliptin; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Eva Johnsson, MD, PhD
• Organization: AstraZeneca

Eva.Johnsson@astrazeneca.com

46 31 7762484

Study Officials

• Changyu Pan, Professor

  The General Hospital of People's liberation Army

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2014
• First Posted: October 23, 2014
• Study Start: December 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: February 5, 2018
• Results First Posted: February 5, 2018

Record last verified: 2017-08

Locations

CN (17)