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

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ClinicalTrials.gov Identifier: NCT03344341
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : July 4, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief 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.

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.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Dapagliflozin Drug: Acarbose Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 900 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 15, 2017
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : August 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dapagliflozin
Dapagliflozin 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.
Drug: Dapagliflozin
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.

Active Comparator: Acarbose
Acarbose 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.
Drug: Acarbose
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.




Primary Outcome Measures :
  1. Absolute change from baseline in HbA1c at Week 24 [ Time Frame: At week 24 ]
    Which will be derived using the HbA1c (%) at week 24 minus HbA1c (%) at baseline.


Secondary Outcome Measures :
  1. Percentage of patients at Week 24 with reduction of HbA1c≥0.5%, body weight≥3% and SBP ≥3mmHg from baseline [ Time Frame: From baseline to week 24 ]
    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.

  2. Percentage of patients achieving HbA1c<7.0% [ Time Frame: From baseline to week 24 ]
    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.

  3. Percentage of patients with reduction of HbA1c≥0.5% [ Time Frame: From baseline to week 24 ]
    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.

  4. Absolute change from baseline in fasting plasma glucose (FPG) [ Time Frame: From baseline to week 24 ]
    Which will be derived using the value of fasting plasma glucose (FPG) at post-baseline visits minus the value at baseline

  5. Absolute change from baseline in 2h postprandial glucose (PPG) [ Time Frame: From baseline to week 24 ]
    Which will be derived using the value of 2h postprandial glucose (PPG) at the post-baseline visits minus the value at baseline

  6. Absolute change from baseline in body weight [ Time Frame: From baseline to week 24 ]
    Which will be derived using the value of the body weight at the post-baseline visits minus the value at baseline

  7. Percentage of patients with reduction of body weight ≥3% [ Time Frame: From baseline to week 24 ]
    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.

  8. Absolute change from baseline in systolic blood pressure (SBP) [ Time Frame: From baseline to week 24 ]
    Which will be derived using the value of the systolic blood pressure at the post-baseline visits minus the value at baseline

  9. Percentage of patients with reduction of SBP ≥3 mmHg [ Time Frame: From baseline to week 24 ]
    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.


Other Outcome Measures:
  1. Homeostasis model assessment-β [ Time Frame: From baseline to week 24 ]
    Which will be used to evaluate the beta cell function.

  2. HOMA-IR [ Time Frame: From baseline to week 24 ]
    Which will be used to evaluate the insulin sensitivity

  3. The difference of the number between tablets taken and tablets prescribed [ Time Frame: From baseline to week 24 ]
    Which will be derived using the number of tablets dispensed minus the number of tablets returned



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. 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.
  2. Diagnosis or history of:

    a. Acute metabolic diabetic complications such as ketoacidosis or hyperglycemic hyperosmolar state b. Diabetes insipidus.

  3. 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.
  4. Triglycerides (fasting) > 9.3 mmol/L (> 800 mg/dL).
  5. 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).
  6. Patients with following renal disease history or renal disease related features:

    1. History of unstable or rapidly progressing renal disease;
    2. Patients with moderate /severe renal impairment or end-stage renal disease (eGFR< 60 mL/min/1.73 m2);
    3. Urinary albumin: creatinine ratio >1800 mg/g;
    4. 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;
    5. Conditions of congenital renal glycosuria.
  7. Severe uncontrolled hypertension defined as SBP ≥180 mmHg and/or BP ≥110 mmHg; Patients with SBP < 95mmHg.
  8. Any of the following cardiovascular diseases within 6 months of the enrollment visit:

    1. Myocardial infarction;
    2. Cardiac surgery or revascularization (coronary artery bypass graft/percutaneous transluminal coronary angioplasty);
    3. Unstable angina;
    4. Congestive heart failure New York Heart Association Class III or IV;
    5. Transient ischemic attack or significant cerebrovascular disease.
  9. History of gastrointestinal disease or surgery including Roemheld Syndrome, severe hernia, intestinal obstruction, intestinal ulcer, gastroenterostomy, enterectomy, bariatric surgery or lap-band procedure.
  10. Malignancy within 5 years of the enrollment visit (with the exception of treated basal cell or treated squamous cell carcinoma).
  11. Known immunocompromised status, including but not limited to, individuals who had undergone organ transplantation or acquired immunodeficiency syndrome (AIDS).
  12. 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.
  13. History of bone fracture secondary to diagnosed severe osteoporosis.
  14. Currently unstable or serious cardiovascular, renal, hepatic, hematologic, oncologic, endocrine, psychiatric, or rheumatic diseases as judged by the Investigator.
  15. Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for >4 weeks within 3 months before enrollment visit.
  16. Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, or phendimetrazine within 30 days of enrollment visit.
  17. Any subject who was currently abusing alcohol or other drugs or had done so within the last 6 months.
  18. 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.
  19. History of hypersensitivity reaction to dapagliflozin or acarbose. Allergies or contraindication to the contents of dapagliflozin tablets or acarbose tablets.
  20. Previous participation in a clinical trial with dapagliflozin.
  21. 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.
  22. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03344341


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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China
Research Site Not yet recruiting
Beijing, China, 100020
Research Site Not yet recruiting
Beijing, China, 100034
Research Site Not yet recruiting
Beijing, China, 100730
Research Site Not yet recruiting
Changsha, China, 410008
Research Site Not yet recruiting
Changsha, China, 410013
Research Site Not yet recruiting
Changsha, China, 430033
Research Site Not yet recruiting
Chengdu, China, 610041
Research Site Not yet recruiting
Chongqing, China, 400016
Research Site Not yet recruiting
Guangzhou, China, 510280
Research Site Not yet recruiting
Guiyang, China
Research Site Recruiting
Hangzhou, China, 310014
Research Site Not yet recruiting
Hangzhou, China, 310016
Research Site Not yet recruiting
Hefei, China, 230022
Research Site Not yet recruiting
Jinan, China, 250012
Research Site Not yet recruiting
Kunming, China, 650032
Research Site Not yet recruiting
Nanjing, China, 2100008
Research Site Not yet recruiting
Nanjing, China, 210029
Research Site Not yet recruiting
Qingdao, China, 266003
Research Site Not yet recruiting
Qingdao, China
Research Site Not yet recruiting
Shanghai, China, 200032
Research Site Recruiting
Shanghai, China, 200233
Research Site Recruiting
Shanghai, China, CN-200120
Research Site Not yet recruiting
Shenyang, China, 100003
Research Site Not yet recruiting
Shenyang, China, 110001
Research Site Not yet recruiting
Suzhou, China, 215004
Research Site Not yet recruiting
Tianjin, China, CN-300070
Research Site Not yet recruiting
Urumqi, China, 830054
Research Site Not yet recruiting
Xi'an, China, 710061
Research Site Not yet recruiting
Xining, China, 810001
Research Site Not yet recruiting
Yinchuan, China, 750004
Sponsors and Collaborators
AstraZeneca
Investigators
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Study Chair: Weiping Jia Shanghai 6th People's Hospital

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.

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03344341     History of Changes
Other Study ID Numbers: D1690C00060
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: July 4, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
T2DM

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Acarbose
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs
Glycoside Hydrolase Inhibitors
Enzyme Inhibitors