Multiple Dose Trial Examining Dose Range, Escalation and Efficacy of Oral Semaglutide 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 the trial is to examine the dose range, escalation and efficacy of oral semaglutide in subjects with type 2 diabetes.

Official Title
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Multiple Dose Trial Examining Dose Range, Escalation and Efficacy of Oral Semaglutide 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: semaglutide
* Drug: oral placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI above or equal to 25 and below or equal to 40 kg/m^2 Subjects diagnosed with T2D (Type 2 diabetes) treated with diet and exercise and/or who have been on a stable dose of metformin for at least 30 days prior to screening HbA1c 7.0-9.5% (53-80 mmol/mol) (both inclusive) Exclusion Criteria: Subjects on selected oral medication with a narrow therapeutic window, such as warfarin, digoxin, tricyclic antidepressants, lithium, aminophylline, theophylline and anticonvulsants History of chronic pancreatitis or idiopathic acute pancreatitis Chronic malabsorption, regardless of aetiology History of Crohn's disease, ulcerative colitis, or other inflammatory bowel disease Treatment with glucose lowering agent(s) other than metformin as stated in the inclusion criteria in a period of 90 days before the screening visit

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: 1:Semaglutide tablets : 2.5 mg<br>2.5 mg for 26 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone. | Drug: semaglutide<br>* Once-daily oral administration as tablets.<br>|
| Experimental: 2:Semaglutide tablets: 2.5 mg/5 mg<br>2.5 mg for 4 weeks, then 5.0 mg for 22 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone. | Drug: semaglutide<br>* Once-daily oral administration as tablets.<br>|
| Experimental: 3:Semaglutide tablets: 5.0 mg/10 mg<br>5.0 mg for 4 weeks, then 10 mg for 22 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone. | Drug: semaglutide<br>* Once-daily oral administration as tablets.<br>|
| Experimental: 4:Semaglutide tablets:5.0 mg/10 mg/20 mg<br>5.0 mg for 4 weeks, then 10 mg for 4 weeks, then 20 mg for 18 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone. | Drug: semaglutide<br>* Once-daily oral administration as tablets.<br>|
| Experimental: 5:Semaglutide tablets:5.0 mg/10 mg/20 mg/40 mg<br>5.0 mg for 4 weeks, then 10 mg for 4 weeks, then 20 mg for 4 weeks, then 40 mg for 14 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone. | Drug: semaglutide<br>* Once-daily oral administration as tablets.<br>|
| Experimental: 6:Semaglutide tablets:5.0 mg/10 mg/20 mg/40 mg<br>5.0 mg for 8 weeks, then 10 mg for 8 weeks, then 20 mg for 8 weeks, then 40 mg for 2 weeks All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone. | Drug: semaglutide<br>* Once-daily oral administration as tablets.<br>|
| Experimental: 7:Semaglutide tablets: 5.0 mg/10 mg/20 mg/40 mg<br>5.0 mg for 2 weeks, then 10 mg for 2 weeks, then 20 mg for 2 weeks, then 40 mg for 20 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone. | Drug: semaglutide<br>* Once-daily oral administration as tablets.<br>|
| Placebo Comparator: 8:Placebo tablets<br>All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone. | Drug: oral placebo<br>* Once-daily oral administration as tablets.<br>|
| Active Comparator: 9:Semaglutide injections :0.25 mg/0.50 mg/1.0 mg<br>0.25 mg for 4 weeks, then 0.50 mg for 4 weeks, then 1.0 mg for 18 weeks. All arms include 26 weeks of treatment and a 5 week follow-up period. The trial medication will be add-on to metformin therapy or as monotherapy in the case where the subject is treated with diet and exercise alone. | Drug: semaglutide<br>* Once-weekly,injected s.c./subcutaneously (under the skin) using a pen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (Glycosylated Haemoglobin) | Change from baseline (week 0) in HbA1c was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation. | Week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects Who Achieve (Yes/no) HbA1c Below 7 Percent (53 mmol/Mol) | Participants who achieved HbA1c <7.0%, was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation. | After 26 weeks of treatment | 
| Change in Body Weight | Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation. | Week 0, Week 26 | 
| Change in Waist Circumference | Change from baseline (week 0) in waist circumference was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation. | Week 0, week 26 | 
| Change in Body Mass Index (BMI) | Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation. | Week 0, week 26 | 
| Number of Treatment Emergent Adverse Events (TEAEs) Recorded | TEAEs were recorded during weeks 0-31 (26 weeks treatment period+5 weeks follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. | Weeks 0-31 | 
| Number of Confirmed Hypoglycaemic Episodes Recorded | Treatment-emergent confirmed hypoglycaemic episodes were recorded during weeks 0-31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Confirmed hypoglycaemic episode is an episode that is severe according to the American Diabetes Association (ADA) classification or plasma glucose value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia. | Weeks 0-31 |