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 | 20.1 |
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 investigate the effect on glycaemic control after 26 weeks treatment of once weekly insulin 287
versus once daily insulin glargine both in combination with metformin with or without dipeptidyl
peptidase-4 inhibitors in insulin-naïve type 2 diabetes mellitus subjects inadequately treated with
metformin with or without dipeptidyl peptidase-4 inhibitors. |
|
E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability during 26 weeks of treatment with once weekly insulin 287
versus once daily insulin glargine both in combination with metformin with or without dipeptidyl
peptidase-4 inhibitors in insulin-naïve subjects with type 2 diabetes mellitus inadequately treated
with metformin with or without dipeptidyl peptidase-4 inhibitors. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent.
- Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening.
- HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory.
- Stable daily dose(s) for 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regime(s):
a) Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's medical record).
b) Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject medical record) with DPP4i (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose (as documented in subject's medical records).
- Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes.
- Body mass index (BMI) less than or equal to 40.0 kg/sqm. |
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E.4 | Principal exclusion criteria |
- Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of screening and between screening and randomisation.
- Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening and between screening and randomisation.
- Presently classified as being in New York Heart Association (NYHA) Class IV.
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes.
- Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g., treatment with orlistat, thyroid hormones, or corticosteroids).
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in glycated haemoglobin (HbA1c) (%-point and
[mmol/mol]) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline (week 0) to week 26 |
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E.5.2 | Secondary end point(s) |
1. Change in fasting plasma glucose (mmol/l)
2. Nine (9)-point profile (individual self-measured plasma glucose (SMPG) values) (mmol/l)
3. Change in mean of the 9-point profile, defined as the area under the profile (mmol/l)
4. Fluctuations of the 9-point profile (defined as the integrated absolute distance from the mean profile value divided by measurement time) (mmol/l)
5. Change in fasting C-peptide (mmol/l)
6. Change in body weight (kilogram)
7. Weekly dose of insulin 287 and weekly dose of IGlar (U)
8. Number of treatment emergent adverse events (TEAEs)
9. Number of hypoglycaemic alert episodes (level 1) (greater than or equal to 3.0 and less than 3.9 mmol/L (greater than or equal to 54 and less than70 mg/dL), confirmed by blood glucose (BG) meter)
10. Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)
11. Number of severe hypoglycaemic episodes (level 3)
12. Change in anti-insulin 287 antibodies level
13. Change in anti-insulin 287 antibody titres
14. Change in cross-reactive anti-human insulin antibody status (positive/negative) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 3, 5 and 6: From baseline (week 0) to week 26
2 and 4: At week 26
7: Week 24-26
8 and 12-14: Baseline (week 0)-week 31
9 – 11: Baseline (week 0)-week 26 |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Canada |
European Union |
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 | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 10 |