Efficacy and safety of semaglutide once-weekly versus exenatide ER 2.0 mg once-weekly as add-on to 1-2 oral antidiabetic drugs (OADs) in subjects with type 2 diabetes

Study ID
STU 102013-012

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Madhuri Poduri
214/648-2321
madhuri.poduri@utsouthwestern.edu

Principal Investigator
Ildiko Lingvay

Summary

This is a 56-weeks randomised, open-label, active-controlled parallel-group, multi-national, multicentre two-armed, efficacy and safety trial comparing semaglutide 1.0 mg once-weekly against exenatide eR 2.0 mg once-weekly. Subjects with type 2 diabetes inadequately controlled with 1-2 oral antidiabetic drugs (oaDs) will be randomised in a 1:1 manner to receive a dose of 1.0 mg semaglutide once-weekly or exenatide eR 2.0 mg once-weekly.
Trial product will be add-on to the subject[?]s stable pre-trial medication consisting of 1-2 of the following compounds: metformin, sulfonylureas (Su) or thiazolidinediones (TZDs).

Primary objective:
To compare the effect of semaglutide 1.0 mg once-weekly versus exenatide eR 2.0 mg once-weekly on glycaemic control after 56 weeks of treatment

Secondary objective:
To compare the effect of semaglutide 1.0 mg once-weekly versus exenatide eR 2.0 mg once-weekly
after 56 weeks of treatment on:
- inducing and maintaining weight loss
- other parameters of efficacy, safety and tolerability

Primary endpoint
- Change from baseline to week 56 in Hba1c

Confirmatory secondary efficacy endpoint
- Change from baseline to week 56 in body weight

Supportive secondary efficacy endpoint
Change from baseline to week 56 in:
- FPG
- Self-measured plasma glucose (SMPG), 7 point profile
o Mean 7-point profile
o Mean post-prandial increment (over all meals)
- insulin, C-peptide, glucagon, pro-insulin, pro-insulin/insulin ratio, homeostasis model assessment of beta-cell function (HoMa-B) and insulin resistance (HoMa-iR) (all fasting)
- Fasting blood lipids (total cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides and free fatty acids)
- Body mass index (BMi)
- Waist circumference
- Systolic and diastolic blood pressure
- Highly sensitive C-reactive protein (hsCRP)
- Patient reported outcome (PRo) questionnaire Diabetes Treatment Satisfaction Questionnaire status (DTSQs) score
- Patient reported outcome (PRo) questionnaire SF-36v2[TM] score

Subjects who after 56 weeks treatment achieve (yes/no):
* -Hba1c [Less Than]7.0% (53 mmol/mol) american Diabetes association (aDa) target
* -Hba1c [LessThanorequalTo]6.5% (48 mmol/mol) american association of Clinical endocrinologists (aaCe) target
* -Weight loss [GreaterThanorequalTo]5%
* -Weight loss [GreaterThanorequalTo]10%
* -Hba1c [Less Than]7.0% (53 mmol/mol) without confirmed (plasma glucose [LessThanorequalTo]3.1 mmol/L) hypoglycaemia and no weight gain

Safety endpoints
* -number of treatment emergent aes during 56 weeks of treatment
* -number of confirmed hypoglycaemic episodes during 56 weeks of treatment
Change from baseline to week 56 in:
* Haematology
* Biochemistry
* Calcitonin
* urinalysis
* urinary albumin to creatinine ratio (uaCR)
* Pulse
* electrocardiogram (eCG) evaluation
* Physical examination evaluation
occurrence of positive semaglutide antibodies during 56 weeks of treatment (yes/no):
- anti-semaglutide antibodies
o anti-semaglutide antibodies with in vitro neutralising effect
o anti-semaglutide antibodies cross reacting with endogenous GLP-1
* --Cross reacting antibodies with in vitro neutralising effect to endogenous GLP-1

anti-semaglutide antibody level during 56 weeks of treatment
occurrence of positive exenatide eR antibodies during 56 weeks of treatment (yes/no):
- anti-exenatide eR antibodies
o anti-exenatide eR antibodies with in vitro neutralising effect
o anti-exenatide eR antibodies cross reacting with endogenous GLP-1
* --Cross reacting antibodies with in vitro neutralising effect to endogenous GLP-1

anti-exenatide eR antibody level during 56 weeks of treatment

endpoint to be included in meta-analyses across phase 3a trials with semaglutide PK-concentrations
- Semaglutide plasma concentration in all subjects randomised to semaglutide 1.0 mg for population PK analyses

Participant Eligibility

1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for
the trial
2. Male or female, age >= 18 years at the time of signing informed consent.
3. Subjects diagnosed with type 2 diabetes and on stable diabetes treatment with 1-2 OADs (Metformin >= 1500 mg or maximum tolerated dose and/or TZD and SUs >= half of maximum dose allowed according to national label) for at least 90 days prior to screening. Stable is defined as unchanged medication and unchanged dose
4. HbA1c 7.0 x 10.5 % (53 x 91 mmol/mol) (both inclusive)