AzTrials
AzTrials

Type 2 Diabetes MellitusPhase 4NCT03344341

A Phase IV Study in Drug-Naive Patients With T2DM in China

A Phase 4 study testing Dapagliflozin and Acarbose in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 20 sites in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a 24-week, multicenter, randomized, open-label, parallel-group, active controlled Phase IV study to assess the efficacy and safety of Dapagliflozin as monotherapy compared with Acarbose in patients with T2DM who were inadequately controlled with diet and exercise. 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?
Dapagliflozin and Acarbose
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
304 participants
Where
20 sitesChina
Study dates
15 Dec 2017to 24 May 2019
Phase
Phase 4
Are there results?
None posted in the registry

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

  • Diagnosed within the past 12 months with T2DM according to 1999 World Health Organization(WHO) criteria.
  • Men and women aged at least 18 years at screening.
  • Either not received oral anti-diabetic drugs or had been on short-term (1 month) treatment that had been discontinued 3 months before enrolment.
  • HbA1c ≥ 7.5% and ≤ 10.5% at screening and HbA1c ≥ 7.0% and ≤ 10.5% at pre-randomization visit.
  • FPG ≤ 13.3 mmol/L (≤ 240 mg/dL) .
  • BMI≥18.5 kg/m2 and ≤ 45.0 kg/m2 .
  • C-peptide ≥0.33nmol/L(≥1.0 ng/mL).
  • Able and willing to provide written informed consent and to comply with the study.

Who cannot join

  • Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods.
  • Diagnosis or history of:
  • Acute metabolic diabetic complications such as ketoacidosis or hyperglycemic hyperosmolar state b. Diabetes insipidus.
  • Requirement for insulin therapy. Symptoms of poorly controlled diabetes, including but not limited to, marked polyuria and polydipsia with >10% weight loss during the 3 months before enrollment.
  • Triglycerides (fasting) > 9.3 mmol/L (> 800 mg/dL).
  • Patients with clinically apparent hepatobiliary disease, including but not limited to chronic active hepatitis and/or severe hepatic insufficiency. Alanine Aminotransferase(ALT) or Aspartate Aminotransferase(AST) > 3x upper limit of normal (ULN), or serum total bilirubin (TB) >34.2 μmol/L (>2 mg/dL).
Show all 33Show fewer
  • Patients with following renal disease history or renal disease related features:
  • History of unstable or rapidly progressing renal disease;
  • Patients with moderate /severe renal impairment or end-stage renal disease (eGFR< 60 mL/min/1.73 m2);
  • Urinary albumin: creatinine ratio >1800 mg/g;
  • Serum creatinine (Cr) ≥133 μmol/L (≥1.50 mg/dL) for male subjects; Serum Cr≥124 μmol/L (≥1.40 mg/dL) for female subjects;
  • Conditions of congenital renal glycosuria.
  • Severe uncontrolled hypertension defined as SBP ≥180 mmHg and/or BP ≥110 mmHg; Patients with SBP < 95mmHg.
  • Any of the following cardiovascular diseases within 6 months of the enrollment visit:
  • Myocardial infarction;
  • Cardiac surgery or revascularization (coronary artery bypass graft/percutaneous transluminal coronary angioplasty);
  • Unstable angina;
  • Congestive heart failure New York Heart Association Class III or IV;
  • Transient ischemic attack or significant cerebrovascular disease.
  • History of gastrointestinal disease or surgery including Roemheld Syndrome, severe hernia, intestinal obstruction, intestinal ulcer, gastroenterostomy, enterectomy, bariatric surgery or lap-band procedure.
  • Malignancy within 5 years of the enrollment visit (with the exception of treated basal cell or treated squamous cell carcinoma).
  • Known immunocompromised status, including but not limited to, individuals who had undergone organ transplantation or acquired immunodeficiency syndrome (AIDS).
  • Any subject who, in the judgment of the investigator, was at risk for dehydration or volume depletion that might affect the interpretation of efficacy or safety data.
  • History of bone fracture secondary to diagnosed severe osteoporosis.
  • Currently unstable or serious cardiovascular, renal, hepatic, hematologic, oncologic, endocrine, psychiatric, or rheumatic diseases as judged by the Investigator.
  • Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for >4 weeks within 3 months before enrollment visit.
  • Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, or phendimetrazine within 30 days of enrollment visit.
  • Any subject who was currently abusing alcohol or other drugs or had done so within the last 6 months.
  • Donation of blood or blood products, blood transfusion, or participation in a clinical study requiring withdrawal of >400 mL of blood during the 6 weeks before the enrollment visit.
  • History of hypersensitivity reaction to dapagliflozin or acarbose. Allergies or contraindication to the contents of dapagliflozin tablets or acarbose tablets.
  • Previous participation in a clinical trial with dapagliflozin.
  • Administration of any other investigational drug within 30 days of planned enrollment to this study, or within 5 half-life periods of other investigational drugs.
  • Subject is, in the judgment of the Investigator, unlikely to comply with the protocol or has any severe concurrent medical or psychological condition that may affect the interpretation of efficacy or safety data.

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

China20 sites

  • Research Site

    Beijing, 100020

  • Research Site

    Beijing, 100730

  • Research Site

    Changsha, 410013

  • Research Site

    Chengdu, 610041

  • Research Site

    Chongqing, 400016

  • Research Site

    Guangzhou, 510280

  • Research Site

    Hangzhou, 310014

  • Research Site

    Hangzhou, 310016

  • Research Site

    Hefei, 230022

  • Research Site

    Jinan, 250012

  • Research Site

    Nanjing, 2100008

  • Research Site

    Qingdao, 266003

  • Research Site

    Qingdao

  • Research Site

    Shanghai, 200233

  • Research Site

    Shanghai, CN-200120

  • Research Site

    Shenyang, 100003

  • Research Site

    Suzhou, 215004

  • Research Site

    Tianjin, CN-300070

  • Research Site

    Xi'an, 710061

  • Research Site

    Yinchuan, 750004

Other trials in China

About this study

Official title: A 24-Week, Multicenter, Randomized, Parallel-group, Open-label, Active Controlled Phase IV Study to Assess the Efficacy and Safety of Dapagliflozin as Monotherapy Compared With Acarbose in Drug-Naive Patients With Type 2 Diabetes Mellitus (T2DM) in China

This is a 24-week, multicenter, randomized, open-label, parallel-group, active controlled Phase IV study to assess the efficacy and safety of Dapagliflozin as monotherapy compared with Acarbose in patients with T2DM who were inadequately controlled with diet and exercise.

The study is designed to evaluate the efficacy and safety of dapagliflozin monotherapy compared with acarbose monotherapy in patients with T2DM inadequately controlled with diet and exercise.

Read the detailed description
  1. Study design This is a 24-week, multicenter, randomized, open-label, parallel-group, active controlled Phase IV study The open-label study design rather than double-blind is considered due to the difficulty of placebo supply. The primary efficacy endpoint will be blinded to both patients and investigators, so the measurements as well as the management of the patients will not be impacted by the design of open-label.

The study is powered to show non-inferiority of dapagliflozin versus acarbose regarding with HbA1c reduction.

A non-inferiority margin of 0.25% for the difference of the reduction in HbA1c is considered in the study.

  1. Primary and secondary outcome variables In the clinical guidelines for type 2 diabetes, HbA1c is recommended as gold standard for determination of glycemic control and is therefore chosen as the primary outcome variable. Certain secondary outcome variables have been selected for additional assessment because of their clinical relevance and importance.
  2. Dosing and study duration Dapagliflozin will be started from 5 mg once a day, taken orally in the morning, before or after food. In patients tolerating dapagliflozin 5 mg once a day, the dose will be increased to 10 mg once a day from the second week.

Acarbose will be started from 50 mg once a day at dinner during the first week and titrated up to 50 mg twice a day at lunch and dinner in the second week, 50 mg three times a day at three meals in the third week, and 100 mg three times a day from the fourth week onwards.

The dosing in study is in line with the local labels for dapagliflozin and acarbose.

Treatment duration of 24 weeks is considered to be adequate to establish glycemic efficacy of dapagliflozin monotherapy compared with acarbose monotherapy in lowering blood glucose indicated by HbA1c change in patients with T2DM inadequately controlled with diet and exercise.

  1. Benefit/risk and ethical assessment According to the available data so far, glucose lowering effect of dapagliflozin is associated with a favourable safety and tolerability profile, and accompanied with a slightly increased risk of genital infection and urinary tract infection [9, 10].

Acarbose is the most widely used oral anti-diabetic drug in china. The common side effects of acarbose treatment are flatulence, borborygmus and diarrhoea, according to the prescribing information and clinical experience from physicians.

The treatment regimens in the study are in line the prescribing information for dapagliflozin and acarbose. Patients with potential contraindications or not considered to get benefit from dapagliflozin or acarbose treatment will be excluded from the study by the inclusion/exclusion criteria set in the study. And the patient safety will be closely monitored in the study by Adverse events/Serious Adverse events collecting and assessment, laboratory testing, ECG, glucometer, vital sign and physical examination.

Overall, the study drugs investigated and the study design is considered to have a favorable benefit-risk profile in the treatment of patients with T2DM.

Methods for assigning treatment groups A block stratified randomization method will be used to assign patients to the treatment groups in this study. Patients will be randomized 1:1 to treatment groups via a central randomization system (interactive voice / web response system [Interactive Voice Response System/Interactive Web Response System])(IVRS/IWRS), and drug will be dispensed accordingly.

The study population will be stratified based on the level of HbA1c at baseline (HbA1c < 8.0%、≥ 8.0% ~ < 9.0% and ≥9.0%)

Being tested
Dapagliflozin, Acarbose
Keywords
T2DM
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

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

  • DapagliflozinDrug

    Starting dose of dapagliflozin is 5 mg once daily, taken orally in the morning, before or after breakfast. From the third week,the dose can be increased to 10 mg once daily, and last to the end of the study.

  • AcarboseDrug

    Acarbose was started from 50 mg once a day at dinner during the first week and titrated up to 50 mg twice a day at lunch and dinner in the second week, 50 mg three times a day at three meals in the third week, and 100 mg three times a day till the end of the study.

Study groups in NCT03344341
Study groupRoleWhat they receive
DapagliflozinExperimentalDapagliflozin is started from 5 mg once a day, taken orally in the morning, before or after breakfast. From the third week, the dose will be increased to 10 mg once a day and last to the end of the study.
Receives: Drug: Dapagliflozin
AcarboseActive comparatorAcarbose is started from 50 mg once a day at dinner during the first week, titrated up to 50 mg twice a day at lunch and dinner in the second week, 50 mg three times a day at three meals in the third week, and 100 mg three times a day till the end of the study.
Receives: Drug: Acarbose

What is being measured

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

  1. Absolute change from baseline in HbA1c at Week 24

    Which will be derived using the HbA1c (%) at week 24 minus HbA1c (%) at baseline.

    Measured: At week 24

Secondary outcomes (9)

  1. Percentage of patients at Week 24 with reduction of HbA1c≥0.5%, body weight≥3% and SBP ≥3mmHg from baseline

    Which will be derived using the number of patients who have reduction in HbA1c ≥ 5%, and body weight ≥3% and SBP ≥3 mmHg compared to baseline divided by the total number of patients.

    Measured: From baseline to week 24

  2. Percentage of patients achieving HbA1c<7.0%

    Which will be derived using the number of patient who have the HbA1c (%) < 7.0% after 24 weeks treatment divided by the total number of patients.

    Measured: From baseline to week 24

  3. Percentage of patients with reduction of HbA1c≥0.5%

    Which will be derived using the number of patients who have reduction in HbA1c≥0.5% after 24 weeks compared to baseline divided by the total number of patients.

    Measured: From baseline to week 24

  4. Absolute change from baseline in fasting plasma glucose (FPG)

    Which will be derived using the value of fasting plasma glucose (FPG) at post-baseline visits minus the value at baseline

    Measured: From baseline to week 24

  5. Absolute change from baseline in 2h postprandial glucose (PPG)

    Which will be derived using the value of 2h postprandial glucose (PPG) at the post-baseline visits minus the value at baseline

    Measured: From baseline to week 24

  6. Absolute change from baseline in body weight

    Which will be derived using the value of the body weight at the post-baseline visits minus the value at baseline

    Measured: From baseline to week 24

  7. Percentage of patients with reduction of body weight ≥3%

    Which will be derived using the number of patients who have reduction in body weight≥3% after 24 weeks compared to baseline divided by the total number of patients.

    Measured: From baseline to week 24

  8. Absolute change from baseline in systolic blood pressure (SBP)

    Which will be derived using the value of the systolic blood pressure at the post-baseline visits minus the value at baseline

    Measured: From baseline to week 24

  9. Percentage of patients with reduction of SBP ≥3 mmHg

    Which will be derived using the number of patients who have reduction in SBP ≥3 mmHg after 24 weeks compared to baseline divided by the total number of patients.

    Measured: From 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.

  1. First posted17 Nov 2017
  2. Study start15 Dec 2017
  3. Primary completion24 May 2019
  4. Study completion24 May 2019

Why it stopped: Study overall progress behind of scheduled timeline. Study was terminated early due to company decision.

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
304 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03344341
Sponsor's protocol ID
D1690C00060
Status last verified
Nov 2021
First submitted
13 Nov 2017
Last updated
7 Dec 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 1. Cefalu, W.T., et al., Dapagliflozin's Effects on Glycemia and Cardiovascular Risk Factors in High-Risk Patients With Type 2 Diabetes: A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With a 28-Week Extension. Diabetes Care, 2015. 38(7): p. 1218-27. 2. Yang, W., et al., Prevalence of diabetes among men and women in China. N Engl J Med, 2010. 362(12): p. 1090-101. 3. Ji, L., et al., Primacy of the 3B approach to control risk factors for cardiovascular disease in type 2 diabetes patients. Am J Med, 2013. 126(10): p. 925.e11-22. 4. 中华医学会糖尿病学分会, 中国2型糖尿病防治指南(2013年版). 中华糖尿病杂志, 2014. 06((07): p. 447-498. 5. Komoroski, B., et al., Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther, 2009. 85(5): p. 513-9. 6. Henry, R.R., et al., Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomised controlled trial. Int J Clin Pract, 2012. 66(5): p. 446-56. 7. Nauck, M.A., et al., Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care, 2011. 34(9): p. 2015-22. 8. 中华医学会糖尿病分会, 中国2型糖尿病防治指南2013年版. 9. Johnsson, K.M., et al., Urinary tract infections in patients with diabetes treated with dapagliflozin. J Diabetes Complications, 2013. 27(5): p. 473-8. 10. Johnsson, K.M., et al., Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J Diabetes Complications, 2013. 27(5): p. 479-84.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dapagliflozin and Acarbose in people with Type 2 Diabetes Mellitus, run by AstraZeneca at 20 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 8 inclusion and 33 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: stopped early, as of the sponsor's last update on 7 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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

Are results available for this study?

The study was stopped early (reason given: Study overall progress behind of scheduled timeline. Study was terminated early due to company decision.). Results are not available in the source record.

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?

Absolute change from baseline in HbA1c at Week 24 (time frame: At week 24). 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 NCT03344341, 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 7 Dec 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in