A Trial Comparing the Safety and Efficacy of Semaglutide Once Weekly in Monotherapy or in Combination With One OAD in Japanese Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Asia. The aim of the trial is to investigate safety and efficacy of semaglutide once weekly in monotherapy or in combination with one OAD (oral anti-diabetic drug) in Japanese subjects with type 2 diabetes who are insufficiently controlled on diet/exercise therapy or OAD monotherapy. All subjects will continue their pre-trial treatment (diet and exercise therapy or OAD monotherapy in addition to diet and exercise therapy) during the trial.

Official Title
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Safety and Efficacy of Semaglutide Once Weekly in Monotherapy or in Combination With One OAD in Japanese Subjects With Type 2 Diabetes Who Are Insufficiently Controlled on Diet/Exercise Therapy or OAD Monotherapy

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: semaglutide
* Drug: DPP-4 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age at least 20 years at the time of signing informed consent HbA1c (glycosylated haemoglobin A1c) between 7.0% and 10.5% (53-91 mmol/mol) (both inclusive) Japanese subjects with type 2 diabetes mellitus (diagnosed clinically) and on stable treatment (defined as unchanged medication and unchanged dose) who are: a) on diet and exercise therapy for at least 30 days before Visit 1 (week -2). or b) on OAD monotherapy (either of SU (sulfonylurea), glinide, a-GI (a-glucosidase inhibitor) or TZD (thiazolidinediones)) within approved Japanese labelling in addition to diet and exercise therapy for at least 60 days before Visit 1 (week -2) Exclusion Criteria: Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (e.g., abstinence [not having sex], diaphragm, condom [by the partner], intrauterine device, sponge, spermicide or oral contraceptives) throughout the trial including the 5 week follow-up period Treatment with glucose lowering agent(s) other than stated in the inclusion criteria within 60 days before Visit 1 (week -2) and treatment with once weekly glucagon-like peptide-1 (GLP-1) receptor agonists within 90 days before Visit 1 (week -2). An exception is short-term treatment (below or equal to 7 days in total) with insulin in connection with inter-current illness Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol History of chronic or idiopathic acute pancreatitis Screening calcitonin value above or equal to 50 ng/L (pg/mL) Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2) Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m^2 per modification of diet in renal disease (MDRD) formula (4 variable version) Acute coronary or cerebrovascular event within 90 days before randomisation (Visit 2 [week 0]) Heart failure, New York Heart Association (NYHA) class IV

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide 0.5 mg<br> | Drug: semaglutide<br>* Subject will receive either a dose of 0.5 or 1.0 mg of semaglutide once weekly (subcutaneous (s.c.) injection).Treatment duration 56 weeks.<br>|
| Experimental: Semaglutide 1.0 mg<br> | Drug: semaglutide<br>* Subject will receive either a dose of 0.5 or 1.0 mg of semaglutide once weekly (subcutaneous (s.c.) injection).Treatment duration 56 weeks.<br>|
| Active Comparator: One additional OAD + pre-trial treatment<br>The type and dosage of the additional OAD will be selected by the investigators according to the approved Japanese labelling including drug combinations and contraindications. One of DPP-4 inhibitor (dipeptidyl peptidase-4), SU (sulfonylurea), glinide, biguanide, α-GI (α-glucosidase inhibitor)or TZD (thiazolidinediones) will be selected as the additional OAD. For the subjects treated with OAD monotherapy as pre-trial treatment, the type and dosage of the additional OAD with a different mechanism of action from the pre-trial OAD should be chosen. | Drug: DPP-4 inhibitor<br>* Subjects will receive one DPP-4 inhibitor in addition to pre-trial OAD monotherapy, if any, for 56 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Emergent Adverse Events (TEAEs) | An adverse event (AEs) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-56 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days). | Weeks 0-56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes | Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <56 mg/dL (3.1 mmol/L), with symptoms consistent with hypoglycaemia. Severe hypoglycaemia: was an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. The episodes mentioned here are treatment emergent hypoglycaemic episodes and defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-56 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days). | Weeks 0-56 | 
| Change in Glycosylated Haemoglobin A1c (HbA1c) | The observed mean change in HbA1c values from baseline after 56 weeks of treatment. Changes in HbA1c were analysed using a mixed model for repeated measurements (MMRM) with treatment and pre-trial treatment at screening as fixed factors and baseline value as covariate. The data were analysed for the on-treatment without rescue medication observation period which includes observations noted at or after the date of first dose of randomised treatment and not after the last dose of the trial product (+ a 7-day visit window) or initiation of rescue medication. | Week 0, week 56 |