E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 14.0 |
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 | 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 confirm the efficacy of IDegAsp twice daily (BID) added to metformin in controlling glycaemia with respect to change from baseline in HbA1c after 26 weeks of treatment. This is done by comparing the difference in change from baseline in HbA1c after 26 weeks of treatment between IDegAsp and BIAsp 30 both BID added to metformin, to a non-inferiority limit of 0.4%, and if noninferiority is confirmed, to a superiority limit of 0%. |
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E.2.2 | Secondary objectives of the trial |
To confirm superiority of IDegAsp BID added to metformin against BIAsp 30 BID added to metformin after 26 weeks of treatment in terms of:
- Fasting plasma glucose (FPG) from central laboratory
- Nocturnal hypoglycaemic episodes (severe and minor)
- Hypoglycaemic episodes (severe and minor)
- Body weight
- Frequency of responders for HbA1c (<7.0 %) without severe or minor hypoglycaemic episodes
To compare efficacy and safety of IDegAsp BID added to metformin against BIAsp 30 BID added to metformin after 26 weeks of treatment in terms of:
- 9-point profile self measured plasma glucose (SMPG)
- 2-point profile (SMPG) for dose adjustments
- Frequency of responders for HbA1c targets
- Adverse Events (AEs)
- Hypoglycaemic episodes
- Clinical and laboratory assessments
- Insulin dose |
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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 procedure that would not have been performed during normal management of the subject.)
- Male or female ≥ 18 years of age
- Type 2 diabetes mellitus (diagnosed clinically) for ≥ 24 weeks
- Current treatment: metformin monotherapy or metformin in any combination with one of the following OADs: insulin secretagogue (sulfonylurea or glinide), dipeptidyl peptidase IV (DPPIV) inhibitor, α-glucosidase inhibitors for at least 12 weeks prior to randomisation (Visit 2) with the minimum doses stated:
- Metformin: alone or in combination (including fixed combination) 1500 mg daily, or maximum tolerated dose (at least 1000 mg daily)
- Insulin secretagogue (sulphonylurea or glinide): minimum half of the daily maximum dose according to local labelling
- DPP-IV inhibitor: minimum 100 mg daily or according to local labelling
- α-glucosidase-inhibitors: minimum half of the daily maximum dose or maximum tolerated dose
- Insulin naïve subject; allowed is:
- Previous short term insulin treatment up to 14 days
- Treatment during hospitalization or during gestational diabetes is allowed for periods longer than 14 days)
- HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis
- Body mass index (BMI) ≤ 40.0 kg/m2 |
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E.4 | Principal exclusion criteria |
- Treatment with thiazolidinedione (TZDs) or GLP-1 receptor agonists within 12 weeks prior to Visit 1
- Anticipated change in concomitant medication known to interfere significantly with glucose metabolism, such as systemic corticosteroids, beta-blockers and MAO inhibitors
- Anticipated significant lifestyle changes during the trial according to the discretion of the investigator, e.g. shift work (including permanent night/evening shift workers), as well as highly variable eating habits
- Cardiovascular disease, within the last 24 weeks prior to visit 1, defined as: stroke; decompensated heart failure NYHA1 class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty
- Any clinically significant disease or disorder, except for conditions associated with type 2 diabetes, which in the Investigator’s opinion could interfere with the results of the trial
- Previous participation in this trial. Participation is defined as randomised. Re-screening of screening failures is allowed only once within the limits of the recruitment period
- Known or suspected hypersensitivity to trial products or related products |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c (%) after 26 weeks of treatment (central laboratory) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 26 weeks of treatment |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in FPG after 26 weeks of treatment (central laboratory)
2. Number of treatment emergent nocturnal (00:01-05:59 am) severe or minor hypoglycaemic episodes
3. Number of severe and minor treatment emergent hypoglycaemic episodes
4. Change from baseline in body weight after 26 weeks of treatment
5. Responder without hypoglycaemic episodes (HbA1c <7.0% at end of trial and no severe or minor hypoglycaemic episodes during the last 12 weeks of treatment including only subjects
exposed for at least 12 weeks) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. After 26 weeks of treatment
2. On or after the first day of exposure to investigational product and no later than 7 days after last exposure to investigational product
3. On or after the first day of exposure to investigational product and no later than 7 days after last exposure to investigational product
4. After 26 weeks of treatment
5. After 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 | 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) | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
Algeria |
Bulgaria |
Croatia |
Czech Republic |
Germany |
Poland |
Romania |
Slovakia |
Turkey |
Ukraine |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 10 |