The renal effects of the new glucose lowering drug dapagliflozin with another glucose lowering drug gliclazide in type 2 diabetes mellitus patients

Phase 1

• Conditions: Type 2 Diabetes Mellitus; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2015-003818-24-NL
• Lead Sponsor: VU University Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-11-10
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

Inclusion criteria
•Caucasian*
•Both genders (females must be post-menopausal; no menses >1 year; in case of doubt, Follicle-Stimulating Hormone (FSH) will be determined with cut-off defined as >31 U/L)
•Age: 35 - 75 years
•BMI: >25 kg/m2
•HbA1c: 6.5 – 9.0% Diabetes Control and Complications Trial (DCCT) or 48 - 86 mmol/mol International Federation of Clinical Chemistry (IFCC)
•Treatment with a stable dose of oral antihyperglycemic agents for at least 3 months prior to inclusion
•Metformin monotherapy
•Combination of metformin and low dose SU derivative**
•Hypertension should be controlled, i.e. =140/90 mmHg, and treated with an ACE-I or ARB (unless prevented by side effect) for at least 3 months.
•Albuminuria should be treated with a RAAS-interfering agent (ACE-I or ARB) for at least 3 months.
•Written informed consent

* In order to increase homogeneity
** In order to accelerate inclusion, patients using combined metformin/SU derivative will be considered. In these patients, a 12 week wash-out period of the SU derivative will be observed, only when combined use has led to a HbA1c <8% at screening. Subsequently, patients will be eligible to enter the study, now using metformin monotherapy, provided that HbA1c still meets inclusion criteria.

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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion Criteria

Exclusion criteria
•History of unstable or rapidly progressing renal disease
•Estimated GFR <60 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation)
•Current/chronic use of the following medication: TZD, SU derivative, GLP-1RA, DPP-4I, SGLT-2 inhibitors, glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). Subjects on diuretics will only be excluded when these drugs cannot be stopped for the duration of the study.
•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.
•Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications (i.e. sports injury, head-ache or back ache). However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing
•History of diabetic ketoacidosis (DKA) requiring medical intervention (eg, emergency room visit and/or hospitalization) within 1 month prior to the Screening visit.
•Current urinary tract infection and active nephritis
•Recent (<6 months) history of cardiovascular disease, including:
oAcute coronary syndrome
oChronic heart failure (New York Heart Association grade II-IV)
oStroke or transient ischemic neurologic disorder
•Complaints compatible with neurogenic bladder and/or incomplete bladder emptying (as determined by ultrasonic bladder scan)
•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
• (Unstable) thyroid disease; defined as fT4 outside of laboratory reference values or change in treatment within 3 months prior to screening visit
•History of or actual malignancy (except basal cell carcinoma)
•History of or actual severe mental disease
•Substance abuse (alcohol: defined as >4 units/day)
•Allergy to any of the agents used in the study
•Individuals who are investigator site personnel, directly affiliated with the study, or are immediate (spouse, parent, child, or sibling, whether biological or legally adopted) family of investigator site personnel directly affiliated with the study
•Inability to understand the study protocol or give informed consent

Study & Design

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