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 | 10027433 - Metabolism and nutrition disorders |
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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 efficacy in terms of glycaemic control of biphasic insulin aspart 30 (BIAsp 30) twice daily + sitagliptin + metformin, BIAsp 30 twice daily + metformin and BIAsp 30 once daily + sitagliptin + metformin in subjects with type 2 diabetes inadequately controlled on sitagliptin and metformin (± other oral anti-diabetic drugs (OADs)) |
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E.2.2 | Secondary objectives of the trial |
To compare the safety, patient reported treatment impact and the health economic consequences of BIAsp 30 twice daily + sitagliptin + metformin, BIAsp 30 twice daily + metformin and BIAsp 30 once daily + sitagliptin + metformin in subjects with type 2 diabetes inadequately controlled on sitagliptin and metformin (± other OADs) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age ≥ 18 years
- Diagnosed with type 2 diabetes for a minimum of 6 months prior to screening (Visit 1)
- Stable treatment with a total daily dose of at least 1000 mg of metformin (± additional OAD treatment). The metformin dose must have been unchanged for at least 3 months prior to screening (Visit 1)
- Stable treatment with a total daily dose of at least 100 mg sitagliptin. The sitagliptin dose must have been unchanged for at least 3 months prior to screening (Visit 1)
- Subject is insulin-naïve (However, short term insulin use due to intermittent illness of up to 14 days or insulin treatment for gestational diabetes is allowed)
- HbA1c 7.0-10.0 % (53-86 mmol/mol) (both inclusive) by central laboratory analysis demonstrating inadequate control on sitagliptin and metformin (± other OADs)
- Body Mass Index (BMI) ≤ 40.0 kg/m^2
- Able and willing to eat at least 2 meals (breakfast and dinner) every day during the trial |
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E.4 | Principal exclusion criteria |
- Treatment with thiazolidinedione (TZD) or glucagon-like-peptide-1 (GLP-1) receptor agonist within the last 3 months prior to screening (Visit 1)
- Cardiac disease, within the last 6 months prior to screening (Visit 1), defined as: decompensated heart failure New York Heart Association (NYHA) class III or IV; unstable angina pectoris; or myocardial infarction
- Severe hypertension, systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≥ 100 mm Hg, after 5 minutes rest in the sitting position using mean value of 3 measurements at screening (Visit 1)
- Anticipated change of dose of any systemic treatment with products, which in the investigator’s opinion could interfere with glucose metabolism (e.g., systemic corticosteroids)
- Clinically significant diseases (except for conditions associated with type 2 diabetes) which, in the investigator’s opinion may confound the results of the trial or pose additional risk in administering trial product(s)
- Impaired hepatic function as indicated by aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) > 2.5 times the upper normal range, according to central laboratory reference ranges
- Impaired renal function as indicated by serum creatinine levels ≥ 133 μmol/L (1.5 mg/dL) for males and ≥ 124 μmol/L (1.4 mg/dL) for females or estimated creatinine clearance below 60 mL/min, based on the Cockroft & Gault formula and according to local practise for metformin use |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c after 24 weeks of treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 24 weeks of treatment |
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E.5.2 | Secondary end point(s) |
Key secondary endpoint supporting primary objective
1. Responder for HbA1c, proportion of subjects achieving pre-defined HbA1c targets after 24 weeks of treatment
2. Change from baseline in fasting plasma glucose (FPG) after 24 weeks of treatment
3. Prandial plasma glucose (PPG) increments at each meal (breakfast, lunch and dinner) and overall mean increment after 24 weeks of treatment
Key secondary safety endpoints supporting the secondary objective
4. Adverse Events (AEs) during the 24 week treatment period
5. Number of treatment emergent hypoglycaemic episodes (nocturnal and day-time) during the 24 week treatment period classified both according to the American Diabetes Association (ADA) definition and to an additional definition for minor episodes
Key secondary efficacy endpoints supporting the secondary objectives
6. Change from baseline in Patient Reported Outcome after 24 weeks of treatment by use of the Treatment Related Impact Measure - Diabetes |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 24 weeks of treatment
2. After 24 weeks of treatment
3. After 24 weeks of treatment
4. During the 24 week treatment period
5. During the 24 week treatment period
6. After 24 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 | No |
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) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
3 different combinations and dosing regimen |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Australia |
Brazil |
Greece |
India |
Korea, Republic of |
Malaysia |
Portugal |
Thailand |
Turkey |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 14 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 14 |