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 | 19.0 |
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 | 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-daily dosing of 14 mg oral semaglutide versus placebo, both in combination with metformin and/or sulfonylurea, basal insulin alone or metformin in combination with basal insulin on glycaemic control in subjects with type 2 diabetes mellitus and moderate renal impairment |
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E.2.2 | Secondary objectives of the trial |
1. To compare the effect of once-daily dosing of 14 mg oral semaglutide versus placebo, both in combination with metformin and/or sulfonylurea, basal insulin alone or metformin in combination with basal insulin on body weight in subjects with type 2 diabetes mellitus and moderate renal impairment.
2. To compare the safety and tolerability of once-daily dosing of 14 mg oral semaglutide versus placebo, both in combination with metformin and/or sulfonylurea, basal insulin alone or metformin in combination with basal insulin in subjects with type 2 diabetes mellitus and moderate renal impairment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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.
3. Diagnosed with type 2 diabetes mellitus ≥ 90 days prior to day of screening.
4. HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive).
5. Moderate renal impairment defined as estimated glomerular filtration rate of 30-59 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula.
6. Stable daily dose(s) within 90 days prior to the day of screening of any of the following treatment regimens:
– 1-2 of the following oral anti-diabetic drugs: - Metformin ≥ 1500 mg or maximum tolerated dose documented in the subject medical record), - Sulfonylurea (≥ half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)
– Basal insulin alone (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin)
or
– Metformin (≥ 1500 mg or maximum tolerated dose documented in the subject medical record) in combination with basal insulin (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin)
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E.4 | Principal exclusion criteria |
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. Rapidly progressing renal disease (e.g. such as acute glomerulonephritis) as judged by the investigator or known nephrotic albuminuria (> 2200 mg/24 hours or > 2200 mg/g).
11. Use of systemic immunosuppressive treatment within 90 days prior to screening.
12. 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.
13. Known hypoglycaemic unawareness and/or recurrent severe hypoglycaemic episodes as judged by the investigator.
14. Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation.
15. History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ).
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in glycosylated haemoglobin (HbA1c) |
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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) |
1. Change in body weight (kg)
2. Change in fasting plasma glucose
3. HbA1c < 7.0% (53 mmol/mol) American Diabetes Association target (yes/no)
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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. + 2. From baseline to week 26
3. After week 26
4. + 5. Assessed up to approximately 31 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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 19 |
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 |
Israel |
Russian Federation |
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 | 4 |
E.8.9.1 | In the Member State concerned days | 2 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 2 |