Dose-finding of Semaglutide Administered Subcutaneously Once Daily Versus Placebo and Liraglutide in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted globally. The aim of this trial is to investigate dose-finding of semaglutide administered subcutaneously once daily versus placebo and liraglutide in subjects with type 2 diabetes

Official Title
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Dose-finding of Semaglutide Administered Subcutaneously Once Daily Versus Placebo and Liraglutide in Subjects With Type 2 Diabetes

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: semaglutide
* Drug: liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age at least 18 years at the time of signing informed consent. Subjects should be on stable diabetes treatment consisting of diet and exercise with or without metformin (at least 1500 mg daily or maximum tolerated dose documented in the patient medical record) for at least 90 days prior to screening HbA1c (glycosylated haemoglobin): 53-86 mmol/mol (7.0-10.0%) (both inclusive) BMI: 25.0 - 40.0 kg/m^2 (both inclusive) Exclusion Criteria: Simultaneous participation in any other clinical trial of an investigational medicinal product Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods throughout the trial including the 7 weeks follow-up period (adequate contraceptive measures as required by local regulation or practice). Germany: Only highly effective methods of birth control are accepted (i.e. one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine device), or sexual abstinence or vasectomised partner. United Kingdom: Adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), female sterilisation, male sterilisation (where partner is sole partner of subject), or true abstinence (when in line with preferred and usual lifestyle) Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before screening (an exception is short-term insulin treatment for acute illnesses for a total of below or equal to 14 days) Anticipated initiation or change in concomitant medications (for more than 14 consecutive days or on an frequent basis) known to affect weight or glucose metabolism (e.g. orlistat, thyroid hormones, corticosteroids) History of pancreatitis (acute or chronic) Screening calcitonin above or equal to 50 ng/L Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN2) or Medullary Thyroid Carcinoma (MTC) Severe to moderate renal impairment defined as GFR, estimated below 60 ml/min/1.73 m^2 as per CKD-EPI (Chronic Kidney Disease Epidemiology) Within the past 180 days before screening any of the following: Myocardial infarction, stroke or hospitalisation for unstable angina and/or transient ischemic attack Currently planned coronary, carotid or peripheral artery revascularisation Patients presently classified as being in New York Heart Association (NYHA) Class III or IV

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide 0.05 mg/day<br> | Drug: semaglutide<br>* Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.<br>|
| Active Comparator: Liraglutide 0.3 mg/day<br> | Drug: liraglutide<br>* Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen.<br>|
| Placebo Comparator: Placebo 50 µL<br> | Drug: placebo<br>* Administered subcutaneously ( s.c., under the skin) once daily.<br>|
| Experimental: Semaglutide 0.05/0.1 mg/day<br> | Drug: semaglutide<br>* Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.<br>|
| Active Comparator: Liraglutide 0.3/0.6 mg/day<br> | Drug: liraglutide<br>* Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen.<br>|
| Placebo Comparator: Placebo 50/100 µL<br> | Drug: placebo<br>* Administered subcutaneously ( s.c., under the skin) once daily.<br>|
| Experimental: Semaglutide 0.05/0.1/0.2 mg/day<br> | Drug: semaglutide<br>* Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.<br>|
| Active Comparator: Liraglutide 0.3/0.6/1.2 mg/day<br> | Drug: liraglutide<br>* Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen.<br>|
| Placebo Comparator: Placebo 50/100/200 µL<br> | Drug: placebo<br>* Administered subcutaneously ( s.c., under the skin) once daily.<br>|
| Experimental: Semaglutide 0.05/0.1/0.2/0.3 mg/day<br> | Drug: semaglutide<br>* Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.<br>|
| Active Comparator: Liraglutide 0.3/0.6/1.2/1.8 mg/day<br> | Drug: liraglutide<br>* Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen.<br>|
| Placebo Comparator: Placebo 50/100/200/300 µL<br> | Drug: placebo<br>* Administered subcutaneously ( s.c., under the skin) once daily.<br>|
| Experimental: Semaglutide flexible escalation from 0.05 mg/day to 0.3 mg/day<br> | Drug: semaglutide<br>* Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (Glycosylated Haemoglobin) | Estimated mean change from baseline in HbA1c at week 26. The data were analysed for the on-treatment until rescue medication observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy. | Week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose (FPG) | Estimated mean change from baseline in FPG at week 26. The data were analysed for the on-treatment until rescue medication observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy. | Week 0, Week 26 | 
| Body Weight Change | The data were analysed for the on-treatment until rescue medication observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy. | Week 0, Week 26 | 
| Change in Systolic and Diastolic Blood Pressure | The data were analysed for the on-treatment until rescue medication observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy. | Week 0, Week 26 |