A clinical trial investigating the effects of dapagliflozin 10 mg on insulin resistance in patients with type 2 diabetes mellitus.

Phase 1

• Conditions: type 2 diabetes mellitus.; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2014-005377-36-FI
• Lead Sponsor: AstraZeneca AB, R&D Mölndal

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-01-20
• Study Completion: 2016-11-29
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

For inclusion in the study subjects should fulfil the following 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 venepuncture
3) Type 2 Diabetes mellitus defined as HbA1c of = 6.5% and = 10.5%.
4) Be on stable (= 3 months) T2D treatment with
• either metformin, sulphonylurea or dipeptidyl peptidase-4 inhibitors (DPP-IV) alone
or
• metformin in combination with sulphonylurea or DPP-IV
5) Have a body mass index (BMI) (measured as body weight (kg)/(height (m))2) = 40 kg/m2.
6) Female subjects must be of non-childbearing potential, meeting at least one of the following criteria:
a) Hysterectomized females
b) Postmenopausal women, defined as women who have not had a menstrual period within 1 year
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1) Involvement in the planning and/or conduct of the study.
2) Previous enrolment in the present study.
3) Participation in another clinical study with an IP during the last 3 months prior to Visit 1.
4) Has any condition that is contraindicated with MRI such as, but not limited to, having a pacemaker or claustrophobia.
5) 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.
6) 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.
7) 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
8) Congestive heart failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure.

Note: eligible patients with congestive heart failure, especially those who are on diuretic therapy, should have careful monitoring of their volume status throughout the study.
9) Blood pressure at enrolment: Systolic BP =165 mm Hg and/or diastolic BP =100 mm Hg
10)Any clinically significant illness, medical or surgical procedure or trauma within 4 weeks of the first administration of IP.
11)On insulin, GLP-1 or other oral antidiabetic drug treatment (metformin, sulphonylurea or DPP-IV, or a combination of metformin with sulphonylurea or DPP-IV allowed) or using other medications known to affect glucose metabolism.
12)Any clinically significant abnormalities in physical examination, Electrocardiography (ECG) or clinical chemistry results at as judged by the investigator. The following specific exclusion criteria apply to the selected Clinical Chemistry results:
a) Creatinine clearance <60mL/min (estimated with Cockroft-Gault formula).
b) 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.
c) Total bilirubin (TB) >2.0 mg/dL (34.2 µmol/L).
13) Recent history (past 12 months) of drug abuse or alcohol abuse. Alcohol abuse is defined as >14 drinks per week (1 drink= 35 cl beer, 14 cl wine or 4 cl hard liquor) or as judged by the investigator.
14) Body weight loss greater than 5% within 3 months prior to Visit 1.
15)Any other condition the investigator believe would interfere with the subject’s ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the subject at undue risk.
16) Plasma donation within one month of Visit 2 or any blood donation/blood loss > 500 mL during 3 months prior to Visit 2.
17) Previous PET scan

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified