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 | 18.1 |
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 | 100000004861 |
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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 |
To compare the effect of once-weekly dosing of two dose levels of semaglutide versus sitagliptin 100 mg once-daily on glycaemic control after 56 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of once-weekly dosing of two dose levels of semaglutide versus sitagliptin 100 mg once-daily after 56 weeks of treatment on:
- Inducing and maintaining weight loss
- Other parameters of efficacy, safety and tolerability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age ≥ 18 years at the time of signing informed consent. For Japan only: Age ≥ 20 years
- Subjects diagnosed with type 2 diabetes and on stable treatment in a period of 90 days prior to screening with either metformin ≥ 1500 mg (or maximum tolerated dose), pioglitazone ≥ 30 mg (or maximum tolerated dose), rosiglitazone ≥ 4 mg (or maximum tolerated dose) or a combination of either metformin/pioglitazone or metformin/rosiglitazone (doses as for individual therapies). Stable is defined as unchanged medication and unchanged dose.
- HbA1c 7.0 – 10.5 % (53 – 91 mmol/mol) (both inclusive) |
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E.4 | Principal exclusion criteria |
- Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using an adequate contraceptive method throughout the trial including the 5 weeks follow-up period (adequate contraceptive measures as required by local law or practice)
- Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject’s safety or compliance with the protocol
- Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term treatment (≤ 7 days in total) with insulin in connection with inter-current illness
- History of chronic or idiopathic acute pancreatitis
- Screening calcitonin value ≥ 50 ng/L (pg/mL)
- Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2)
- Impaired renal function defined as eGFR < 60 ml/min/1.73 m2 per modification of diet in renal disease (MDRD) formula (4 variable version)
- Acute coronary or cerebrovascular event within 90 days before randomisation
- Heart failure, New York Heart Association (NYHA) class IV |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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) |
Confirmatory efficacy endpoint:
1. Change in body weight
Supportive efficacy endpoints:
Change in:
2. Fasting Plasma Glucose (FPG)
3. Systolic and diastolic blood pressure
4. Patient reported outcome (PRO) questionnaire Diabetes Treatment Satisfaction Questionnaire status (DTSQs)
These endpoints will be evaluated as the mean treatment differences.
Subjects who achieve (yes/no):
5. HbA1c ≤6.5% (48 mmol/mol) American Association of Clinical Endocrinologists (AACE) target
This endpoint will be evaluated as the odds ratio between treatments. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Confirmatory efficacy endpoint:
1. From baseline to week 56
Supportive efficacy endpoints:
2.-4. From baseline to week 56
5. After 56 weeks treatment
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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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 4 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
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 |
European Union |
Hong Kong |
India |
Japan |
Mexico |
Norway |
Russian Federation |
South Africa |
Thailand |
Turkey |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 16 |