Type 2 Diabetes MellitusPhase 3NCT02273050

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

A Phase 3 study testing Saxagliptin 5 mg and Metformin 500 mg with titration in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 17 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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 Read more about this study

Who is it for?: Ages 18 to 100 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: Saxagliptin 5 mg and Metformin 500 mg with titration
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,136 participants
Where: 17 sitesChina
Study dates: Dec 2014to Aug 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 100 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

17 sites in 1 country.

City, postcode or hospital

17 sites in 1 country

China17 sites

Research Site
Beijing
Research Site
Changchun
Research Site
Chuangchun
Research Site
Fuzhou
Research Site
Guiyang
Research Site
Ha’erbin
Research Site
Hangzhou
Research Site
Hefei
Research Site
Jinan
Research Site
Nanchang
Research Site
Nanjing
Research Site
Shanghai
Research Site
Shijiazhuang
Research Site
Siping
Research Site
Tianjin
Research Site
Wuxi
Research Site
Yueyang

Other trials in China

About this study

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

Read the detailed description

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

Conditions: Type 2 Diabetes Mellitus
Being tested: Saxagliptin 5 mg, Placebo 5 mg for Saxagliptin, Placebo 500 mg for metformin (with titration), Metformin 500 mg with titration
Keywords: Type 2 Diabetes Mellitus, Dipeptidyl-Peptidase 4 Inhibitors, Saxagliptin, Metformin, Endocrine System Diseases
Medical subject headings: Diabetes Mellitus, Type 2, Endocrine System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Saxagliptin 5 mgDrug
Also called Onglyza, BMS-477118
Tablet, Oral, 5 mg, Once daily in the morning
Placebo 5 mg for SaxagliptinDrug
Tablet, Oral, 5 mg, Once daily in the morning
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.
Metformin 500 mg with titrationDrug
Also called Glucophage
Tablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration.

Study groups in NCT02273050
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Drug: Placebo 5 mg for Saxagliptin; Drug: Metformin 500 mg with titration

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline to Week 24 (prior to rescue)

Secondary outcomes (6)

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.
Measured: Week 24 (prior to rescue)
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.
Measured: 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
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.
Measured: Baseline to Week 24 prior to rescue
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.
Measured: Week 24 (prior to rescue)
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.
Measured: Baseline to Week 24 prior to rescue
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.
Measured: Baseline to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2014Aug 2016

First posted23 Oct 2014 (estimated)
Study startDec 2014
Primary completionAug 2016
Study completionAug 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 1,136 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02273050
Sponsor's protocol ID: D1680C00009
Status last verified: Aug 2017
First submitted: 22 Oct 2014
Last updated: 5 Feb 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 28926170

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02273050
Acronym / sponsor ID: D1680C00009
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 Diabetes Mellitus, Dipeptidyl-Peptidase 4 Inhibitors, Saxagliptin, Metformin, Endocrine System Diseases
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,136 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Dec 2014
Primary completion: Aug 2016 (actual)
Study completion: Aug 2016 (actual)
First posted: 23 Oct 2014 (estimated)
Results: Posted 5 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Saxagliptin 5 mg + Metformin (500 mg with titration)	Experimental	Drug: Saxagliptin 5 mg, Drug: Metformin 500 mg with titrationSaxagliptin 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
Saxagliptin 5 mg + Placebo	Active comparator	Drug: Saxagliptin 5 mg, Drug: Placebo 500 mg for metformin (with titration)Saxagliptin 5 mg once daily and Placebo 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.
Metformin (500 mg with titration) + Placebo	Active comparator	Drug: Placebo 5 mg for Saxagliptin, Drug: Metformin 500 mg with titrationPlacebo 5 mg once daily and metformin 500 mg once daily, then titrate. Acarbose will be used as rescue medication as needed.

Who may qualify

Ages: 18 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

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.

Key exclusion criteria (1 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Saxagliptin 5 mgAlso: Onglyza, BMS-477118Tablet, Oral, 5 mg, Once daily in the morning	Drug	Saxagliptin 5 mg + Metformin (500 mg with titration), Saxagliptin 5 mg + Placebo
Placebo 5 mg for SaxagliptinTablet, Oral, 5 mg, Once daily in the morning	Drug	Metformin (500 mg with titration) + Placebo
Placebo 500 mg for metformin (with titration)Tablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration.	Drug	Saxagliptin 5 mg + Placebo
Metformin 500 mg with titrationAlso: GlucophageTablet, 500 mg, Once daily in the evening the first two weeks and thereafter according to titration.	Drug	Metformin (500 mg with titration) + Placebo, Saxagliptin 5 mg + Metformin (500 mg with titration)

Primary outcome

Change From Baseline in HbA1c From Baseline to Week 24 Provided That it is Prior to Rescue
Time frame: Baseline to Week 24 (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.

6 secondary outcomes

Glycemic Response Defined as HbA1c < 7.0% at Week 24
Time frame: Week 24 (prior to rescue)
Change From Baseline to Week 24 (Prior to Rescue) in Fasting Plasma Glucose
Time frame: 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
Time frame: Baseline to Week 24 prior to rescue
Glycemic Response Defined as HbA1c ≤ 6.5% at Week 24
Time frame: Week 24 (prior to rescue)
Change From Baseline to Week 24 in 120-minute Postprandial Glucose Response to a Meal Tolerance Test
Time frame: Baseline to Week 24 prior to rescue
Patients Rescued for Failing to Achieve Pre-specified Glycemic Targets or Discontinuation for Lack of Efficacy During the 24-week Double-blind Treatment Phase
Time frame: Baseline to Week 24

Results and safety

Results posted to the registry on 5 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
METFORMIN + PLACEBO 5MG QD	210	186
SAXAGLIPTIN 5MG QD + METFORMIN	216	194
SAXAGLIPTIN 5MG QD + PLACEBO	214	185

Primary outcome: Change From Baseline in HbA1c From Baseline to Week 24 Provided That it is Prior to Rescue

Time frame: Baseline to Week 24 (prior to rescue). Least squares mean (Standard Error). Unit: % HbA1c

Measure	Saxagliptin + Metformin n = 209	Saxagliptin + Placebo n = 212	Metformin + Placebo n = 204
Value	-3.007 (0.0706)	-2.123 (0.0701)	-2.794 (0.0715)

Saxagliptin + Metformin vs Saxagliptin + Placebo: Mean Difference (Net): -0.885 (95% CI -1.080 to -0.689), p <0.001, ANCOVA
Saxagliptin + Metformin vs Metformin + Placebo: Mean Difference (Net): -0.213 (95% CI -0.410 to -0.016), p = 0.034, ANCOVA

Population analysed: The full analysis set consisted of patients who were randomized, took at least 1 randomized study medication, and had both a baseline and at least 1 post-baseline efficacy assessment for the time point under consideration.

6 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
METFORMIN + PLACEBO 5MG QD	11 of 210 (5.2%)	30 of 210 (14.3%)	Not reported
SAXAGLIPTIN 5MG QD + METFORMIN	4 of 215 (1.9%)	37 of 215 (17.2%)	Not reported
SAXAGLIPTIN 5MG QD + PLACEBO	12 of 214 (5.6%)	21 of 214 (9.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28926170Dou 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.

Related trials for Type 2 Diabetes Mellitus

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Changyu Pan, Professor principal investigator

The General Hospital of People's liberation Army

17 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Saxagliptin 5 mg and Metformin 500 mg with titration in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 17 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in HbA1c From Baseline to Week 24 Provided That it is Prior to Rescue (time frame: Baseline to Week 24 (prior to rescue)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02273050, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2018.