Dapagliflozin + Saxagliptin in a Basal-bolus Insulin Treatment (DapaSaxaBBIT)

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

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.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Dapagliflozin 10 mg + Saxagliptin 5 mg; Drug: Placebo 1 10 mg + Placebo 2 5 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • University Hospital Tübingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Verum; Dapagliflozin 10 mg + Saxagliptin 5 mg, each once daily, for 24 weeks	Drug: Dapagliflozin 10 mg + Saxagliptin 5 mg; 24 weeks intervention with Dapagliflozin 10 mg + Saxagliptin 5 mg; Other Names: Forxiga + Onglyza
PLACEBO_COMPARATOR: Placebo; Placebo 1 10 mg + Placebo 2 5 mg, each once daily, for 24 weeks	Drug: Placebo 1 10 mg + Placebo 2 5 mg; 24 weeks intervention with Placebo 1 10 mg + Placebo 2 5 mg; Other Names: Placebo 1 + Placebo 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in HbA1c between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in hypoglycaemic events between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in fasting blood glucose between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in daily insulin dose between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in bodyweight between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in body fat content between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in body fat distribution between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in liver fat content between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in intra-nasal insulin-induced brain fMR (functional magnetic resonance) imaging results between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in blood pressure between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in the blood lipid profile between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in microalbuminuria between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in well being and disease perception between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in fear of hypoglycemia between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in fetuin-A levels between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in adiponectin levels between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in (Interleucin 1?ßß) IL-1ß levels between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in Il-6 levels between groups	treatment of dapagliflozin/saxagliptinn or placebo	24 weeks
differences in adverse events between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
differences in severe adverse events between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
differences in heart rate between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
differences in ECG parameters between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks
changes in clinical chemistry/haematology parameters between groups	treatment of dapagliflozin/saxagliptin or placebo	24 weeks

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 2, 2018
• Primary Completion (ACTUAL): February 3, 2020
• Study Completion (ACTUAL): February 3, 2020

Study Registration Dates

• First Submitted: October 28, 2016
• First Submitted That Met QC Criteria: November 11, 2016
• First Posted (ESTIMATE): November 16, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Dapagliflozin; Saxagliptin
• Other Study ID Numbers: UTUB - 2015-005740-34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No