A study to evaluate the efficacy and safety of dapagliflozin and dapagliflozin in combination with saxagliptin in type 2 diabetes with kidney disease.

• Register: EUCTR
• Last refreshed on: 14 May 2018
• Main ID: EUCTR2015-002676-24-ES
• Date of registration: 05/10/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A study to evaluate the efficacy and safety of dapagliflozin and dapagliflozin in combination with saxagliptin in type 2 diabetes with kidney disease.
• Scientific title: An exploratory Phase II/III, randomized, double-blind, placebo controlled, parallel design study to evaluate the efficacy, safety and pharmacodynamics of dapagliflozin and dapagliflozin in combination with saxagliptin in CKD3 patients with type 2 diabetes mellitus and albuminuria treated with ACEi or ARB. - DELIGHT
• Date of first enrolment: 24/11/2015
• Target sample size: 1125
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002676-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Japan, Mexico, Spain, Taiwan, United States

Contacts

• Name: Unidad de Investigación Clínica
• Affiliation: AstraZeneca Farmacéutica Spain, S.A.

• Name: Unidad de Investigación Clínica
• Affiliation: AstraZeneca Farmacéutica Spain, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of informed consent prior to any study specific procedures 2. Female or male aged > o = 18 years and < 75 years. 3. History of type 2 diabetes mellitus for more than 12 months 4. Inadequate glycemic control, defined as HbA1c > o = 7.5% and < o = 10.5%. 5. Stable antidiabetic treatment during the last 12 weeks up to randomization.Stable antidiabetic treatment regimen, defined as: Stable diet and exercise therapy alone or in combination with any or both of the two following alternatives a.A regimen of any approved oral anti-diabetic medication (except SGLT2 inhibitors, GLP-1 receptor agonists and DPP4 inhibitors) where no dosechanges have occurred during the last 12 weeks up to randomization. b.Long acting or intermediate acting insulin and mixed insulin permitted as long as the dose is stable 12 weeks before randomization, changes ± 10% are allowed (in relation to number of units at randomization). 6. Renal impairment defined as eGFR 30 - 59 mL/minute/1.73 m^2, inclusive. 7. Micro or macroalbuminuria (UACR 30 - 3500 mg/g, inclusive). 8. Patient must be receiving an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) for at least 3 months prior to screening, where the dose of the ACE inhibitor or the ARB is considered appropriate for that patient, and has been stable and maintained on that dose for at least 4 weeks prior to study randomization.
9. Body mass index between 20 and 40 kg/m^2, inclusive.
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 225
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 225

Exclusion criteria:
Main exclusion criteria are:- History of ?2 major hypoglycaemic events in the 3 months prior to enrolment visit, defined as symptomatic events
requiring external assistance due to severe impairment in consciousness or behaviour, with blood glucose level <3.0 mmol/L, <54 mg/dL (plasma glucose level <3.5 mmol/L, <63 mg/dL) and prompt recovery after glucose or glucagon administration.- Patients with Type 1 DM, history of diabetes insipidus, diabetic ketoacidosis, hyperosmolar nonketotic coma- Severe uncontrolled hypertension or any CV/Vascular Diseases within 3 month prior to signing the following: - Myocardial infarction. - Cardiac surgery or revascularization.- Unstable angina.- Unstable heart failure.- HF
New York Heart Association Class III-IV.- Transient ischemic attack or
significant cerebrovascular disease.- Unstable or previously undiagnosed arrhythmia.-Significant hepatic disease, severe hepatobiliary disease or hepatotoxicity with any medication- History of haemoglobinopathy or acute kidney injury requiring renal replacement therapy or any biopsy or imaging verifying intercurrent kidney disease other than diabetic nephropathy or diabetic nephropathy with nephrosclerosis.- History of unexplained microscopic or gross haematuria, or microscopic haematuria, confirmed by a follow-up sample at next scheduled visit- Treatment with a SGLT2 inhibitor, GLP-1 agonist or DPP4 inhibitors.- Simultaneous treatment with both an ACEi and an ARB- A metformin dose which is outside the specified dose range for moderate renal impairment (eGFR 30-59 mL/minute/1.73 m^2,) according to local guidelines and investigators judgement.- Any condition which, in the ju gment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk or suspected risk to the patient or with confirmed poor protocol or medication compliance - Patients at risk for volume depletion as judged by the investigator.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

CKD3 patients with type 2 diabetes mellitus and albuminuria.
MedDRA version: 18.0 Level: LLT Classification code 10045250 Term: Type II diabetes mellitus with renal manifestations System Organ Class: 100000004857

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: Forxiga
Product Name: Dapagliflozin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Dapagliflozin propanediol
CAS Number: 960404-48-2
Other descriptive name: DAPAGLIFLOZIN PROPANEDIOL MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Onglyza
Product Name: Saxagliptin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Saxagliptin
CAS Number: 361442-04-8
Other descriptive name: SAXAGLIPTIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: ·To compare the mean percent change from baseline in total body weight, and to compare the mean change from baseline in fasting plasma glucose or seated systolic blood pressure between dapagliflozin 10 mg plus saxagliptin 2.5 mg and placebo. ·To compare the proportion of patients achieving a 30% reduction in Urine albumin-to-creatinine ratio or a reduction in HbA1c <7.0% between dapagliflozin 10 mg plus saxagliptin 2.5 mg and placebo. ·To compare the mean percent change from baseline in total body weight and to compare the mean change from basleine in seated systolic blood pressure, HbA1c, or fasting plasma glucose between dapagliflozin 10 mg and placebo. ·To compare the proportion of patients achieving a 30% reduction in Urine albumin-to-creatinine ratio or a reduction in HbA1c <7.0% between dapagliflozin 10 mg and placebo.

Primary end point(s): Outcome Measure for the Saxagliptin/Dapagliflozin treatment
arm?Change from baseline in HbA1c at Week 24.- Percent change from
baseline in UACR at Week 24 Outcome Measure for the Dapagliflozin
treatment arm.- Percent change from baseline in UACR at Week 24

Main Objective: Primary objectives for the Saxagliptin/Dapagliflozin treatment arm
- To compare the mean change from baseline in HbA1c between dapagliflozin 10 mg plus saxagliptin 2.5 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes and CKD stage 3.- To compare the mean percent change from baseline in urine albumin-to creatinine ratio (UACR) between dapagliflozin 10 mg plus saxagliptin 2.5 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes and CKD stage 3. Primary objective for the Dapagliflozin treatment arm. - To compare the mean percent change from baseline in urine albumin-to creatinine ratio
(UACR) between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes and CKD stage 3.

Timepoint(s) of evaluation of this end point: Baseline to end of treatment

Secondary Outcome(s)

Secondary end point(s): Outcome Measure for the Saxagliptin/Dapagliflozin treatment arm: 1.
Percent change from baseline in total body weight at Week 24 2. Change from baseline in FPG at Week 24 3. 30% reduction in UACR at Week 24 4. HbA1c < 7.0 % at Week 24 5. Change from baseline in seated SBP at Week 24 Outcome Measure for the Dapagliflozin treatment arm: 1. Percent change from baseline in total body weight at Week 24 2. 30% reduction in UACR at Week 24 3. Change from baseline in seated SBP at Week 24 4. Change from baseline in HbA1c at Week 24 5. Change from baseline in FPG at Week 24 6. HbA1c < 7.0 % at Week 24

Timepoint(s) of evaluation of this end point: Baseline to the end of treatment

Secondary ID(s)

D1690C00023

Source(s) of Monetary Support

AstraZeneca AB