Dapagliflozin + Saxagliptin in a Basal-bolus Insulin Treatment

Type 2 Diabetes Clinical Trial

— DapaSaxaBBIT  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02965443
• Other study ID #: UTUB - 2015-005740-34
• Status: Terminated
• Phase: Phase 4
• Start date: February 2, 2018
• Est. completion date: February 3, 2020

Study information

• Verified date: May 2018
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: February 3, 2020
• Est. primary completion date: February 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Dapagliflozin 10 mg + Saxagliptin 5 mg
24 weeks intervention with Dapagliflozin 10 mg + Saxagliptin 5 mg
• Placebo 1 10 mg + Placebo 2 5 mg
24 weeks intervention with Placebo 1 10 mg + Placebo 2 5 mg

Locations

Country	Name	City	State
Germany	University Hospital Tübingen	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	changes in fetuin-A levels between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Other	changes in adiponectin levels between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Other	changes in (Interleucin 1?ßß) IL-1ß levels between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Other	changes in Il-6 levels between groups	treatment of dapagliflozin/saxagliptinn or placebo	24 weeks
Other	differences in adverse events between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Other	differences in severe adverse events between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Other	differences in heart rate between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Other	differences in ECG parameters between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Other	changes in clinical chemistry/haematology parameters between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Primary	Percentage of subjects achieving a HbA1c = 7.5% and having a reversal from a BBIT to a BOT regimen	Percentage of subjects achieving a HbA1c = 7.5% and having a reversal from a BBIT to a BOT regimen with treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in HbA1c between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in hypoglycaemic events between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in fasting blood glucose between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in daily insulin dose between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in bodyweight between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in body fat content between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in body fat distribution between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in liver fat content between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in intra-nasal insulin-induced brain fMR (functional magnetic resonance) imaging results between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in blood pressure between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in the blood lipid profile between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in microalbuminuria between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in well being and disease perception between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
Secondary	changes in fear of hypoglycemia between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks