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 | 14.1 |
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 confirm superiority of switch from sitagliptin 100 mg/day to liraglutide 1.8 mg/day, both + metformin vs. continued sitagliptin 100 mg/day + metformin on glycaemic control after 26 weeks of treatment in subjects with type 2 diabetes. |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of switch from sitagliptin 100 mg/day to liraglutide 1.8 mg/day, both + metformin vs. continued sitagliptin 100 mg/day + metformin after 26 weeks of treatment in subjects with type 2 diabetes.
- selected parameters of anthropometry
- selected cardiovascular risk factors
- safety and tolerability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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
- Male or female, age ≥ 18 years
- Subjects diagnosed with type 2 diabetes and treated with metformin ≥ 1500 mg/day (or maximum tolerated dose ≥ 1000 mg/day) and sitagliptin 100 mg/day, both at a stable dose for at least 90 days prior to screening. Stable is defined as unchanged medication and dose
- HbA1c 7.5% – 9.5% (58 mmol/mol – 80 mmol/mol) (both inclusive)
- Body mass index ≥ 20 kg/m^2 |
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E.4 | Principal exclusion criteria |
- Any chronic disorder or severe disease which at the discretion 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 prior to screening. An exception is short-term treatment (≤ 7 days in total) with insulin in connection with intercurrent illness
- Female who is pregnant, breast-feeding, intends to become pregnant or of child-bearing potential not using adequate contraceptive methods (adequate contraceptive measures as required by local regulations or practice)
- History of chronic pancreatitis or idiopathic acute pancreatitis
- Screening calcitonin value ≥ 50 ng/L
- Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
- Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)
- Impaired liver function, defined as alanine aminotransferase ≥ 2.5 times upper normal limit
- Impaired renal function defined as estimated glomerular filtration rate < 60 mL/min/1.73 m^2 per modification of diet in renal disease formula
- Any episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack or other significant cardiovascular event as judged by the investigator within 90 days prior to screening
- Heart failure, New York Heart Association class IV
- Uncontrolled treated or untreated hypertension (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥100 mmHg) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c
This endpoint will be evaluated as the mean treatment difference. |
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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 secondary endpoint
1. Change in body weight
This endpoint will be evaluated as the mean treatment difference.
Key supportive secondary endpoints
Change in:
2. Fasting plasma glucose
3. Fasting blood lipids
4. Systolic blood pressure and diastolic blood pressure
These endpoints will be evaluated as the mean treatment differences.
Subjects who achieve (y/n):
5. HbA1c < 7.0% (53 mmol/mol) (American Diabetes Association target)
This endpoint will be evaluated as the odds ratio between treatments.
Safety endpoints
6. Number of treatment emergent adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Confirmatory secondary endpoint
1. - 4. From baseline to Week 26
5. After 26 weeks of treatment
6. During 26 weeks of 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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 |
European Union |
Canada |
India |
Israel |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 6 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 6 |