Effects of Dapagliflozin 10 mg on Insulin Resistance in Patients With Type 2 Diabetes Mellitus

NCT ID: NCT02426541

Last Updated: 2018-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-23
• Study Completion Date: 2016-04-28

Brief Summary

This is an 8-week, single centre, randomized, parallel-group, double-blind, placebo-controlled Phase IV study to evaluate the effect of dapagliflozin on tissue specific insulin sensitivity in patients with Type 2 diabetes mellitus

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Dapagliflozin

Dapagliflozin Once Daily 10 mg

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks

Placebo

Matching placebo for Dapagliflozin Once Daily 10 mg

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo to Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks

Interventions

Dapagliflozin

Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks

Intervention Type: DRUG

Placebo

Matching placebo to Dapagliflozin 10 mg Tablets, Oral, Once Daily, 8 weeks

Intervention Type: DRUG

Other Intervention Names

Forxiga, Farxiga

Eligibility Criteria

Inclusion Criteria

1. Provision of signed informed consent prior to any study specific procedures.

2. Female or male aged 35 to 70 years inclusive with suitable veins for cannulation or repeated venipuncture

3. Type 2 Diabetes mellitus defined as HbA1c of ≥ 6.5% and ≤ 10.5%.

4. Stable (≥ 3 months) T2D treatment with metformin and/or metformin+dipeptidyl peptidase-4 inhibitors (DPP-IV)

5. Body mass index (BMI) ≤ 40 kg/m2.

6. Female subjects must be of non-childbearing potential, meeting at least one of the following criteria:

1. Hysterectomized females

2. Postmenopausal women, defined as women who have not had a menstrual period within 1 year

Exclusion Criteria

1. Any condition that is contraindicated with MRI such as, but not limited to, having a pacemaker or claustrophobia.

2. Volume depleted patients. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status.

3. Recent Cardiovascular Events in a patient:

• Acute Coronary Syndrome (ACS) within 2 months prior to enrolment
• Hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment
• Acute Stroke or Transient Ischemic Attack (TIA) within two months prior to enrolment
• Less than two months post coronary artery revascularization

4. Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure.

5. Blood pressure at enrolment: Systolic BP ≥165 mm Hg and/or diastolic BP ≥100 mm Hg

6. Any clinically significant illness, medical or surgical procedure or trauma within 4 weeks of the first administration of the investigational product.

7. On insulin, GLP-1 or other oral antidiabetic drug treatment (metformin or both metformin and DPP-IV allowed) or using other medications known to affect glucose metabolism.

1. Creatinine clearance <60mL/min (estimated with Cockroft-Gault formula).

2. Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN.

3. Total bilirubin (TB) >2.0 mg/dL (34.2 µmol/L).

9. Body weight loss greater than 5% within 3 months prior to Visit 1.

10. Previous PET scan

11. History of or presence of (as found at Visit 1) any clinically significant disease, disorder or condition which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Antaros Medical

INDUSTRY

Sponsor Role: collaborator

Bioventure Hub

UNKNOWN

Sponsor Role: collaborator

43183 Mölndal

UNKNOWN

Sponsor Role: collaborator

Sweden

UNKNOWN

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pirjo Nuutila, MD, PhD, Professor

Role: PRINCIPAL_INVESTIGATOR

Turku PET Centre, Turku, Finland

Locations

Research Site

Turku, , Finland

Countries

Finland

References

Latva-Rasku A, Honka MJ, Kullberg J, Mononen N, Lehtimaki T, Saltevo J, Kirjavainen AK, Saunavaara V, Iozzo P, Johansson L, Oscarsson J, Hannukainen JC, Nuutila P. The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients. Diabetes Care. 2019 May;42(5):931-937. doi: 10.2337/dc18-1569. Epub 2019 Mar 18.

Reference Type: DERIVED

PMID: 30885955 (View on PubMed)

Other Identifiers

2014-005377-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D1690C00025

Identifier Type: -

Identifier Source: org_study_id