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

NCT02426541 | Completed Phase 4 Results

• 2 other identifiers: D1690C000252014-005377-36
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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

Keywords

Diabetes Mellitus; Dapagliflozin; Placebo; Insulin resistance; Insulin sensitivity

Outcome Measures

Primary Outcomes (1)

• Adjusted Change From Baseline in Skeletal Muscle Insulin-stimulated Gluocose Uptake

  Adjusted change from baseline in skeletal muscle insulin-stimulated gluocose uptake (umol/min/kg)

  From baseline to Week 8

Secondary Outcomes (2)

• Adjusted Change in Adipose Tissue Insulin-stimulated Glucose Uptake

  Baseline to Week 8

• Adjusted Change in Liver Insulin-stimulated Glucose Uptake From Baseline to Week 8

  Baseline to Week 8

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

Dapagliflozin Once Daily 10 mg

Drug: Dapagliflozin

Placebo

PLACEBO COMPARATOR

Matching placebo for Dapagliflozin Once Daily 10 mg

Drug: Placebo

Interventions

Dapagliflozin DRUG

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

Also known as: Forxiga, Farxiga

Dapagliflozin

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed informed consent prior to any study specific procedures.
• Female or male aged 35 to 70 years inclusive with suitable veins for cannulation or repeated venipuncture
• Type 2 Diabetes mellitus defined as HbA1c of ≥ 6.5% and ≤ 10.5%.
• Stable (≥ 3 months) T2D treatment with metformin and/or metformin+dipeptidyl peptidase-4 inhibitors (DPP-IV)
• Body mass index (BMI) ≤ 40 kg/m2.
• Female subjects must be of non-childbearing potential, meeting at least one of the following criteria:
• Hysterectomized females
• Postmenopausal women, defined as women who have not had a menstrual period within 1 year

You may not qualify if:

• Any condition that is contraindicated with MRI such as, but not limited to, having a pacemaker or claustrophobia.
• 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.
• 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
• Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure.
• Blood pressure at enrolment: Systolic BP ≥165 mm Hg and/or diastolic BP ≥100 mm Hg
• Any clinically significant illness, medical or surgical procedure or trauma within 4 weeks of the first administration of the investigational product.
• 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.
• Creatinine clearance \<60mL/min (estimated with Cockroft-Gault formula).
• 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.
• Total bilirubin (TB) \>2.0 mg/dL (34.2 µmol/L).
• Body weight loss greater than 5% within 3 months prior to Visit 1.

Sponsors & Collaborators

• AstraZeneca: lead
• Antaros Medical: collaborator
• Bioventure Hub: collaborator
• 43183 Mölndal: collaborator
• Sweden: collaborator

Study Sites (1)

Research Site

Turku, Finland

Location

Related Publications (1)

• 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.

  PMID: 30885955 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Insulin Resistance

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Results Point of Contact

• Title: Anna Maria Langkilde
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Pirjo Nuutila, MD, PhD, Professor

  Turku PET Centre, Turku, Finland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: April 27, 2015
• Study Start: March 23, 2015
• Primary Completion: April 28, 2016
• Study Completion: April 28, 2016
• Last Updated: February 5, 2018
• Results First Posted: February 5, 2018

Record last verified: 2017-07

Locations

FI (1)