A Clinical Study to Investigate the Effects of Dapagliflozin on Heart Work, Heart Nutrient Uptake, and Heart Muscle Efficiency in Type 2 Diabetes Patients

NCT03387683 | Completed Phase 4 Results

• 2 other identifiers: D1690C000632017-003820-58
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a randomised, placebo-controlled, double-blind, parallel-group, international, multicentre, Phase IV study to investigate the effects of dapagliflozin on cardiac substrate uptake, myocardial efficiency and myocardial contractile work in T2D patients. Eligible subjects with T2D before randomisation and fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomised in a 1:1 ratio to dapagliflozin 10 mg or placebo once daily and treated for six weeks. The study includes five visits.

Conditions

Diabetes Mellitus Type 2

Outcome Measures

Primary Outcomes (1)

• Adjusted Mean Change From Baseline in Global Longitudinal Strain of the Left Ventricle (GLSLV) at End of Treatment.

  Patients underwent magnetic resonance imaging (MRI) examination to determine the GLSLV, which is expressed as a percentage. The least square mean (LSM) change from baseline estimates were generated from an analysis of covariance (ANCOVA) model with treatment and baseline value of the endpoint as covariates.

  Baseline (Day 1) and end of treatment (Day 42)

Secondary Outcomes (1)

• Adjusted Mean Change From Baseline in Myocardial Efficiency at End of Treatment.

  Baseline (Day 1) and end of treatment (Day 42)

Study Arms (2)

placebo

PLACEBO COMPARATOR

placebo tablets once daily

Drug: placebo

dapagliflozin 10mg

EXPERIMENTAL

dapagliflozin 10mg tablets once daily

Drug: dapagliflozin

Interventions

dapagliflozin DRUG

dapagliflozin 10mg

Also known as: Forxiga 10mg

dapagliflozin 10mg

placebo DRUG

placebo to match dapagliflozin

placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
• Females or males ≥40 years up to 75 years of age.
• Individuals with type 2 diabetes diagnosed for at least 6 months based on the American Diabetes Association standards (ADA, 2017) and on stable dose of metformin for at least 6 weeks prior to screening and HbA1c at screening visit of ≥42 mmol/mol (6.0%) and ≤75 mmol/mol (9.0%) measured at local hospital laboratory.
• No significant signs or symptoms of coronary artery disease or, if known coronary artery disease, currently free of symptoms and a) all major epicardial vessels with \<50% stenosis within 12 months prior to screening, or b) if revascularized with all major epicardial vessels with \<50% remaining stenosis after stenting or bypass surgery procedure determined between 3 and 12 months prior to screening.
• Normal left ventricular ejection fraction (≥50%) assessed within 1 year prior to informed consent, and if applicable, after most recent acute episode of coronary artery syndrome, or at screening visit.
• Body mass index (BMI) ≥ 25 kg/m2.

You may not qualify if:

• Blood pressure at screening that would require a change in blood pressure treatment over the study period or any of the following: systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg.
• History of stroke or other clinically significant cerebrovascular disease.
• Any of the following cardiovascular diseases known within 3 months prior to signing the consent at enrolment:
• Atrial fibrillation, or other unstable or severe arrhythmia affecting heart function
• Unstable heart failure or any heart failure with NYHA class III and IV
• Significant valvular disease
• Significant peripheral artery disease
• Planned cardiac surgery or angioplasty within 3 months from enrolment.
• Clinical diagnosis of type 1 diabetes, maturity onset diabetes of the young (MODY), secondary diabetes or diabetes insipidus.
• Verified body weight variability of \>3 kg during the 3 proceeding months before screening.
• Active malignancy requiring treatment at the time of visit 1 (with the exception of successfully treated basal cell or treated squamous cell carcinoma).
• Patients with severe hepatic impairment (Child-Pugh class C).
• Unstable or rapidly progressing renal disease.
• Clinically significant disease or disorder 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.
• Ongoing treatment with other antidiabetic drugs than metformin.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Turku, 20520, Finland

Location

Research Site

Uppsala, SE-751 85, Sweden

Location

Related Links

• redacted SAP
• redacted CSP

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

+1 302 885 1180

Study Officials

• Jonas Oldgren, MD, PhD

  Uppsala Clinical Research Center, Upppsala Sweden

  PRINCIPAL INVESTIGATOR

• Pirjo Nuutila, MD, PhD

  University of Turku, Turku, Finland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: January 2, 2018
• Study Start: February 28, 2018
• Primary Completion: March 19, 2019
• Study Completion: March 19, 2019
• Last Updated: April 27, 2020
• Results First Posted: March 25, 2020

Record last verified: 2020-04

Locations

SE (1); FI (1)