Clinical trial NCT02965443: Dapagliflozin + Saxagliptin in a Basal-bolus Insulin Treatment
Official title: Effectiveness of Dapagliflozin + Saxagliptin to Revert From a Basal-bolus Insulin Treatment (BBIT) Regimen to a Basal Supported Oral Therapy (BOT) in Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Type 2 Diabetes
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2016-11-16
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To perform a study that investigates the effectiveness of adding the SGLT2 inhibitor dapagliflozin + the dipeptidyl peptidase 4 (DPP-4) inhibitor saxagliptin vs placebo to revert from a BBIT regimen to a BOT regimen in patients with type 2 diabetes.

Detailed description: This will be a phase IV study investigating the efficacy and safety of adding the SGLT2 inhibitor dapagliflozin together wih the DPP-4 inhibitor saxagliptin to an intensified insulin treatment regimen. Because BOT is superior to BBIT in respect to the development of bodyweight, hypoglycaemia and patient satisfaction in type 2 diabetes, we hypothesize that the combined addition of the SGLT2 inhibitor dapagliflozin with the DPP-4 inhibitor saxagliptin is effective and safe to revert from a BBIT to a BOT treatment regimen.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes
* Age 18 - 75 years
* Anti-GAD antibodies negative (Glutamic Acid Decarboxylase)
* C-peptide levels ≥ 1.5 ng/mL
* Fasting blood glucose \> 126 mg/dl
* HbA1c 8.0 - 10.5 %
* BMI 25.0 - 45.0 kg/m2
* Previous therapy with BBIT (basal insulin and at least once daily bolus insulin)

Exclusion Criteria:

* Use of any oral antidiabetic treatment except for metformin (i.e., sulphonylureas, DPP-IV inhibitors, thiazolidinediones, SGLT-2 inhibitors (Sodium dependent glucose transporter) or GLP-1 analogues (glucagone like peptide) within the last three months prior to Screening
* Repeated episodes of severe hypoglycaemia within the last six months prior to Screening
* History of diabetic ketoacidosis, precoma diabetica, or diabetic coma
* Treatment with any other investigational drug within the last three months before Screening
* Acute infections within the last four weeks prior to Screening
* Recurrent urogenital infections
* History of pancreatitis
* Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures
* History of severe or multiple allergies
* Concomitant participation in other clinical trials
* Type 1 diabetes
* Cardiovascular disease Clinically relevant ventricular tachycardia or ventricular fibrillation, 3rd degree AV block or Torsades de Pointes or treatment with antiarrhythmic drugs. Percutaneous coronary intervention within the past 6 months. Any of the following within the past 6 months: myocardial infarction (MI), coronary artery bypass surgery; unstable angina; or stroke.

Uncontrolled unstable angina pectoris or history of pericarditis, myocarditis, endocarditis. Congestive heart failure NYHA (New York Heart Association) class III or IV. Increased risk of thromboembolism, e.g. subjects with a history of deep leg vein thrombosis or family history of deep leg vein thrombosis, as judged by the Investigator.

* Malignancy including leukemia and lymphoma within the last 5y.
* Liver disease such as cirrhosis or chronic active hepatitis.
* Significant renal dysfunction (see also exclusion criteria laboratory abnormalities).
* State after kidney transplantation
* Endocrine disease:

Acromegaly or treatment with growth hormone or similar drugs. Chronic oral or parenteral corticosteroid treatment (\>7 consecutive days of treatment) within 8 weeks; thyroid hormone replacement is allowed if the dosage has been stable for at least 3 months and the TSH is within normal limits

•Any of the following significant laboratory abnormalities: eGFR (as calculated by the MDRD equation) \< 60 ml/min at Screening Fasting triglycerides \>700 mg/dl (\>7.9 mmol/l)

* Systolic blood pressure outside the range of 100-160 mmHg or diastolic blood pressure above 95 mmHg at Screening
* History of active substance abuse (including alcohol \> 40g/day) within the past 2 years.
* Pregnancy or childbearing potential without adequate contraception
* Present therapy with systemic steroids
* Presence of psychiatric disorder or intake of anti-depressive or anti-psychotic agents with the exception of benzodiazepines and SSRIs/SNRI´s (selective serotonin reuptake inhibitor)
* Potentially unreliable subjects, and those judged by the investigator to be unsuitable for the study.
* Contraindications for Magnetic resonance (MR) scanning such as persons with cardiac pacemaker and implants out of metal or claustrophobia

Primary outcomes:
measure: Percentage of subjects achieving a HbA1c ≤ 7.5% and having a reversal from a BBIT to a BOT regimen
timeFrame: 24 weeks
Secondary outcomes:
measure: changes in HbA1c between groups
timeFrame: 24 weeks
measure: changes in hypoglycaemic events between groups
timeFrame: 24 weeks
measure: changes in fasting blood glucose between groups
timeFrame: 24 weeks
measure: changes in daily insulin dose between groups
timeFrame: 24 weeks
measure: changes in bodyweight between groups
timeFrame: 24 weeks
measure: changes in body fat content between groups
timeFrame: 24 weeks
measure: changes in body fat distribution between groups
timeFrame: 24 weeks
measure: changes in liver fat content between groups
timeFrame: 24 weeks
measure: changes in intra-nasal insulin-induced brain fMR (functional magnetic resonance) imaging results between groups
timeFrame: 24 weeks
measure: changes in blood pressure between groups
timeFrame: 24 weeks
measure: changes in the blood lipid profile between groups
timeFrame: 24 weeks
measure: changes in microalbuminuria between groups
timeFrame: 24 weeks
measure: changes in well being and disease perception between groups
timeFrame: 24 weeks
measure: changes in fear of hypoglycemia between groups
timeFrame: 24 weeks
Other outcomes:
measure: changes in fetuin-A levels between groups
timeFrame: 24 weeks
measure: changes in adiponectin levels between groups
timeFrame: 24 weeks
measure: changes in (Interleucin 1?ßß) IL-1ß levels between groups
timeFrame: 24 weeks
measure: changes in Il-6 levels between groups
timeFrame: 24 weeks
measure: differences in adverse events between groups
timeFrame: 24 weeks
measure: differences in severe adverse events between groups
timeFrame: 24 weeks
measure: differences in heart rate between groups
timeFrame: 24 weeks
measure: differences in ECG parameters between groups
timeFrame: 24 weeks
measure: changes in clinical chemistry/haematology parameters between groups
timeFrame: 24 weeks
Locations:
city: Tübingen
country: Germany
facility: University Hospital Tübingen
Study officials:
References: