E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000072461 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Main phase: To compare the effect of once-daily dosing of oral semaglutide using a flexible dose adjustment based on clinical evaluation versus sitagliptin once-daily, both in combination with 1-2 oral antidiabetic drugs (OADs) on glycaemic control in subjects with Type 2 diabetes mellitus (T2DM). |
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E.2.2 | Secondary objectives of the trial |
Main phase
To compare
- the effect on body weight
- the safety and tolerability
of once-daily dosing of oral semaglutide using a flexible dose adjustment based on clinical evaluation versus sitagliptin once daily, both in combination with 1-2 OADs in subjects with T2DM.
Extension phase (sustainability)
To evaluate
- the sustainability of glycaemic control and body weight reduction
- the long term safety
of once-daily dosing of oral semaglutide using a flexible dose adjustment based on clinical evaluation in subjects with T2DM.
Extension phase (switch)
To compare
- the effect on glycaemic control
- the effect on body weight
- the safety and tolerability
of switching to once-daily dosing of oral semaglutide using a flexible dose adjustment based on clinical evaluation versus staying on oncedaily
sitagliptin in subjects with T2DM. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main phase (the inclusion criteria for the main phase are not reassessed for the extension phase):
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 above or equal to 18 years at the time of signing informed consent. For Korea only: Male or female, age above or equal to
19 years at the time of signing informed consent.
3. Diagnosed with type 2 diabetes mellitus ≥ 90 days prior to day of screening.
4. HbA1c 7.5-9.5% (58-80 mmol/mol) (both inclusive).
5. Treatment target of HbA1c < 7.0% (53 mmol/mol), as judged by the investigator.
6. Stable daily dose(s) of 1-2 of the following anti-diabetic drugs within 90 days prior to the day of screening:
– Metformin (≥1500 mg or maximum tolerated dose as documented in the subject medical record).
– Sulfonylureas (≥ half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record).
– Sodium glucose co-transporter 2 inhibitors.
– Thiazolidinediones (≥ half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record).
Extension phase:
7. Informed consent for the extension phase obtained before any trial-related activities for the extension phase.
8. On randomised treatment with or without rescue medication at week 52. |
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E.4 | Principal exclusion criteria |
Main phase (the exclusion criteria for the main phase are not reassessed for the extension phase):
1. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate
contraceptive method (adequate contraceptive measure as required by local regulation or practice). For certain specific countries: Additional specific requirements apply.
2. Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol.
3. Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma.
4. History of pancreatitis (acute or chronic).
5. History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy,
sleeve gastrectomy, gastric bypass surgery).
6. Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation.
7. Subjects presently classified as being in New York Heart Association Class IV.
8. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.
9. Subjects with alanine aminotransferase > 2.5 x upper normal limit.
10. Renal impairment defined as Estimated Glomerular Filtration rate < 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology
Collaboration formula.
11. 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 the day of screening. An exception is short-term insulin treatment for acute illness for a total of ≤ 14 days.
12. Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation.
13. History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ).
14. History of diabetic ketoacidosis.
Extension phase:
There are no new exclusion criteria for the extension phase. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Main phase:
Glycosylated haemoglobin (HbA1c) < 7% (53 mmol/mol) American
Diabetes Association target (yes/no) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Main phase:
1. Change in body weight (kg)
2. Change in HbA1c
3. Change in fasting plasma glucose
4. Number of treatment-emergent adverse events during exposure to trial product
5. Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes during exposure to trial product
Ext phase (sustainability):
1. If a subject achieves (yes/no) HbA1c < 7% (53 mmol/mol) American Diabetes Association target.
2. Change in body weight (kg)
3. Change in HbA1c
4. Change in fasting plasma glucose (FPG)
5. Number of treatment-emergent adverse events during exposure to trial product,
6. Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes during exposure to trial product
Ext phase (switch):
7. If a subject achieves (yes/no) HbA1c < 7% (53 mmol/mol) American Diabetes Association target.
8. Change in body weight (kg)
9. Change in HbA1c
10. Change in fasting plasma glucose (FPG)
11. Number of treatment-emergent adverse events during exposure to trial product
12. Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes during exposure to trial product |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Main phase:
1.-3. From baseline to week 52
4.+ 5. Assessed up to approximately 52 weeks
Ext phase (sustainability)
1.: After week 104
2. – 4.: From baseline to week 104
5. – 6.: Assessed up to approximately 109 weeks
Ext phase (switch)
7.: After week 104
8. – 10.: From week 52 to 104
11. – 12.: Assessed from week 52 up to approximately 109 weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Egypt |
European Union |
Korea, Republic of |
Norway |
Switzerland |
Turkey |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 11 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 11 |