A trial to investigate the efffect of a SGLT-2 inhibitor a DPP-4 inhibitor and a SGLT-2 inhibitor + DPP-4 inhibitor on glucagon levels, endogenous glucose production and lipolysis.

• Register: EUCTR
• Last refreshed on: 13 February 2017
• Main ID: EUCTR2015-004637-27-AT
• Date of registration: 14/12/2015
• Prospective Registration: Yes
• Primary sponsor: Medizinische Universität Graz
• Public title: A trial to investigate the efffect of a SGLT-2 inhibitor a DPP-4 inhibitor and a SGLT-2 inhibitor + DPP-4 inhibitor on glucagon levels, endogenous glucose production and lipolysis.
• Scientific title: A randomized, double-blind, three arm, three treatment period, cross-over trial to investi-gate the effect of a SGLT-2 inhibitor, a DPP-4 inhibitor and a SGLT-2 inhibitor + DPP-4 inhibitor on glucagon levels, endogenous glucose production and lipolysis during hyper-, normo- and hypoglycaemia in subjects with type 2 diabetes using stable tracer technique.
• Date of first enrolment: 21/01/2016
• Target sample size: 18
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004637-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no 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: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria

Contacts

• Name: Study Coordinator
• Affiliation: Medizinische Universität Graz

• Name: Study Coordinator
• Affiliation: Medizinische Universität Graz

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female aged 18-64 years (both inclusive) at the time of signing informed consent.
• Subjects diagnosed with type 2 diabetes and on stable treatment for a period of 90 days prior to screening with metformin as monotherapy. Stable is defined as un-changed dose.
• Body mass index (BMI) between 20.0 and 35.0 kg/m2 (both inclusive).
• HbA1c between 47.5 and 85.8 mmol/mol (6.5 – 10.0%) (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 18
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Treatment with any glucose lowering agent(s) other than metformin in a period of 90 days before screening. An exception is short-term treatment (= 7 days in total) with insulin due to intercurrent illness.
• Clinically significant abnormal haematology, biochemistry, lipids, hormones, coagu-lation and urinalysis.
• Acute symptomatic (according to investigator’s judgement) urinary tract infection or genital infection, chronic or recurrent (= 3 annual episodes) cystitis.
• Uncontrolled hypertension defined as sitting blood pressure at screening (after resting for 5 min) outside the range of 90-160 mmHg for systolic or 50-100 mmHg for diastolic.
• Chronic liver failure with severe liver dysfunction as assessed by the investigator.



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

Health Condition(s) or Problem(s) studied

Diabetes mellitus type 2
MedDRA version: 19.0 Level: LLT Classification code 10012594 Term: Diabetes System Organ Class: 100000004861

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

Intervention(s)

Trade Name: Forxiga 10 mg
Pharmaceutical Form: 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-
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use

Trade Name: Onglyza
Pharmaceutical Form: 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: Coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): ?Glucagon: Change in glucagon concentration from 5.5 mmol/L low insulin to 11.1 mmol/L: Glucagon11.1-Glucagon.

Timepoint(s) of evaluation of this end point: At each plateau of the hyper-, normo- and hypoglycaemic clamp

Main Objective: To compare the glucagon response of a treatment with metformin monotherapy (baseline), a SGLT-2 inhibitor, a DPP-4 inhibitor and a combination of a SGLT-2 inhibitor and a DPP-4 inhibitor during normo-, hyper- and hypoglycaemia in a controlled clamp setting under stable metformin therapy.

Secondary Objective: To compare the effect of treatment with metformin monotherapy (baseline), an add-on SGLT-2 inhibitor, an add-on DPP-4 inhibitor and an add-on combination of a SGLT-2 inhibitor and a DPP-4 inhibitor on endogenous glucose production, peripheral glucose uptake, lipolysis, insulin sensitivity, metabolites, and glucose regulating hormones during normo-, hyper- and hypoglycaemia in a controlled clamp setting under stable metformin therapy.

Secondary Outcome(s)

Secondary end point(s): AUCGlucagon: area under the complete glucagon concentration curve during the clamp procedure.
GlucagonPG, glucagon concentration at different assessment plateaus (e.g. 11.1 mmol/L)
?Glucagona,b, change in glucagon concentration between different glucose levels (e.g. change from 5.5 mmol/L low insulin to 11.1 mmol/L)
EGPplateau, mean endogenous glucose production (EGP) at different assessment plateaus (e.g. assessment plateau 11.1 mmol/L)
?EGPa,b, change in EGP between different assessment plateaus (e.g. change from assessment plateau 5.5 mmol/L low insulin to 11.1 mmol/L)
AUCGIR, area under the glucose infusion rate (GIR) curve at different assessment plateaus (e.g. assessment plateau 11.1 mmol/L)
?GIRa,b, change in AUCGIR between different assessment plateaus (e.g. change from assessment plateau 5.5 mmol/L low insulin to 11.1 mmol/L)
PGUplateau, mean peripheral glucose uptake (PGU) at different assessment plateaus (e.g. assessment plateau 11.1 mmol/L)
?PGUa,b, change in PGU between different assessment plateaus (e.g. change from assessment plateau 5.5 mmol/L low insulin to 11.1 mmol/L)
Lipoplateau, mean lipolysis at different assessment plateaus (e.g. assessment plateau 11.1 mmol/L)
?lipoa,b, change in lipolysis between different assessment plateaus (e.g. change from assessment plateau 5.5 mmol/L low insulin to 11.1 mmol/L)
MetabolPG, concentration of lactate, free fatty acids, glycerol and ketone bodies at different assessment plateaus(e.g. 11.1 mmol/L)
?Metabola,b, change in concentration of lactate, free fatty acids, glycerol and ketone bodies between different glucose levels (e.g. change from 5.5 mmol/L low insulin to 11.1 mmol/L)
CounterPG, concentration of adrenaline, noradrenaline, growth hormone and cortisol at different assessment plateaus (e.g. 11.1 mmol/L)
?Countera,b, change in concentration of adrenaline, noradrenaline, growth hormone and cortisol between different glucose levels (e.g. change from 5.5 mmol/L low insulin to 11.1 mmol/L)

Timepoint(s) of evaluation of this end point: At each plateau of the hyper-, normo- and hypoglycaemic clamp

Secondary ID(s)

AZ-01_SGLT-2

Source(s) of Monetary Support

Medizinische Universität Graz