Effect of Saxagliptin in Addition to Dapagliflozin and Metformin on Insulin Resistance, Islet Cell Dysfunction, and Metabolic Control in Subjects with Type 2 Diabetes Mellitus on Previous Metformin Treatment

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2014-003788-39-DE
• Date of registration: 27/10/2014
• Prospective Registration: Yes
• Primary sponsor: Profil Mainz GmbH & Co KG
• Public title: Effect of Saxagliptin in Addition to Dapagliflozin and Metformin on Insulin Resistance, Islet Cell Dysfunction, and Metabolic Control in Subjects with Type 2 Diabetes Mellitus on Previous Metformin Treatment
• Scientific title: Effect of Saxagliptin in Addition to Dapagliflozin and Metformin on Insulin Resistance, Islet Cell Dysfunction, and Metabolic Control in Subjects with Type 2 Diabetes Mellitus on Previous Metformin Treatment
• Date of first enrolment: 17/12/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003788-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Germany

Contacts

• Name: Prof. Dr. Thomas Forst
• Affiliation: Profil Mainz GmbH & Co KG

• Name: Prof. Dr. Thomas Forst
• Affiliation: Profil Mainz GmbH & Co KG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Diabetes mellitus type 2
2. HbA1c 7.0%–9.9%, both inclusive
3. Treatment with metformin for at least six months (daily dose 1500 – 3000 mg)
4. Age 30–75 years, both inclusive
5. BMI 25–35 kg/m^2, both 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 21
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Use of any oral antidiabetic treatment except for metformin (i.e., sulphonylureas, DPP-IV inhibitors, thiazolidinediones, SGLT-2 inhibitors) within the last three months prior to Screening
2. Use of insulin or GLP-1 analogues within three months prior to Screening
3. Treatment with any other investigational drug within three months before screening
4. History of diabetes mellitus type 1



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

Health Condition(s) or Problem(s) studied

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

Type 2 Diabetes mellitus
MedDRA version: 17.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Intervention(s)

Trade Name: Forxiga
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DAPAGLIFLOZIN
CAS Number: 461432-26-8
Other descriptive name: DAPAGLIFLOZIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Onglyza
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SAXAGLIPTIN
Other descriptive name: SAXAGLIPTIN HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate alpha- and beta-cell function during combination treatment with dapagliflozin plus saxagliptin compared to dapagliflozin alone in subjects with T2DM on stable metformin background therapy

Secondary Objective: •evaluate the effect of dapagliflozin treatment on alpha- and beta-cell function in subjects with T2DM
•evaluate insulin resistance during combination treatment with dapagliflozin plus saxagliptin compared to dapagliflozin alone in subjects with T2DM
•evaluate the effect of dapagliflozin treatment on insulin resistance in subjects with T2DM
•evaluate body weight during combination treatment with dapagliflozin plus saxagliptin compared to dapagliflozin alone in subjects with T2DM
•evaluate the effect of dapagliflozin treatment on body weight in subjects with T2DM
•evaluate the risk of hypoglycaemia during combination treatment with dapagliflozin plus saxagliptin compared to dapagliflozin alone in subjects with T2DM
•evaluate the effect of dapagliflozin treatment on the risk of hypoglycaemic events in subjects with T2DM

Primary end point(s): • Glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc270–390min / AUCIns270–390min)

Timepoint(s) of evaluation of this end point: Endpoint measurements will be performed at baseline (Visit 2) as well as after Treatment Phase 1 (Visit 3) and after Treatment Phase 2 (Visit 3)

Secondary Outcome(s)

Secondary end point(s): •Glucagon release during hyperglycaemic clamp phase (AUCGluc270–390min; pg/ml*min)
•First phase glucagon release during hyperglycaemic clamp phase (AUCGluc270–290min; pg/ml*min)
•First phase insulin release during hyperglycaemic clamp phase (AUCIns270–290min; pmol/l*min)
•Second phase insulin release during hyperglycaemic clamp phase (AUCIns290–390min; pmol/l*min)
•First Phase glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc270–290min / AUCIns270–290min)
•Second Phase glucagon / insulin ratio during hyperglycaemic clamp phase (AUCGluc290–390min / AUCIns290–390min)
•Intact proinsulin release during hyperglycaemic clamp (AUCIP270–390min ; pmol/l*min)
•Insulin / proinsulin ratio during hyperglycaemic clamp (AUCIns270–390min / AUCIP270–390min)
•C-Peptide release during hyperglycaemic clamp (AUCC-Pep270–390min ; pmol/l*min)
•C-Peptide/Insulin ratio during hyperglycaemic clamp (AUCC-Pep270–390min / AUCIP270–390min)
•M-Value during euglycaemic-hyperinsulinaemic clamp phase (mg/kg*min)
•HOMAIR Index
•Body Weight (kg)
•Fasting Adiponectin (µg/ml)
•Fasting Plasma Glucose (mg/dl)
•HbA1C (mmol/mol; %)
•QuantoseTM Score
•Blood Lipids (Triglycerides [mg/dl]; total, HDL, LDL cholesterol [mg/dl])
•Incidence of treatment-emergent hypoglycaemic episodes from baseline (first administration of trial medication on Visit 2) until end of treatment (last administration of trial medication on Visit 4)
•Changes in clinical and laboratory safety variables from baseline until end of treatment
•Incidence of adverse events from baseline until end of Treatment

Timepoint(s) of evaluation of this end point: Endpoint measurements will be performed at baseline (Visit 2) as well as after Treatment Phase 1 (Visit 3) and after Treatment Phase 2 (Visit 3)

Secondary ID(s)

ESR-14-10231

Source(s) of Monetary Support

Astra Zeneca