E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
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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 SIBA ± OAD(s) in a flexible dosing regimen 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 SIBA ± OAD(s) in a flexible dosing regimen and insulin glargine ± OAD(s) to a non-inferiority limit of 0.4%, and if non-inferiority is confirmed, to a superiority limit of 0%. |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of SIBA ± OAD(s) in a flexible regimen to the efficacy of SIBA ± OAD(s) in a fixed regimen in terms of change from baseline in HbA1c after 26 weeks of treatment.
To compare the efficacy and safety after 26 weeks of treatment between the three treatment groups in terms of: • Frequency of responders for HbA1c • Frequency of responders for HbA1c without hypoglycaemic episodes • Fasting plasma glucose (FPG) from central laboratory • Hypoglycaemic episodes • 9-point profile (SMPG) • Prandial plasma glucose (PG) increment • Selfmeasured plasma glucose for dose adjustments • Glucose profile as measured with CGM in a sub-population • Insulin dose • Body weight • Adverse events • Clinical and laboratory assessments • Insulin antibodies • Patient reported outcome
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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 defined as any procedure that would not have been performed during standard management of the subject). 2. Male or female ≥ 18 years of age 3. Type 2 diabetes mellitus (diagnosed clinically) for ≥ 6 months 4. Current treatment: OAD(s) alone, basal insulin alone or the combination of OAD(s) and basal insulin. Allowed OADs (alone or in combination with basal insulin) are: Metformin, insulin secretagogues (sulphonylureas (SU) or glinides), pioglitazone with unchanged dosing for at least 3 months prior to Visit 1 with the minimum doses stated: a. Metformin: alone or in combination (including fixed combination) 1500 mg daily, or maximum tolerated dose (at least 1000 mg daily) b. Insulin secretagogue (sulfonylurea or glinide): Minimum half of the daily maximal dose according to local labelling c. Pioglitazone: Minimum half of the daily maximal dose according to local labelling or maximum tolerated dose 5. HbA1c: OADs only users 7.0-11.0 % (both inclusive), basal insulin ± OADs users 7.0-10.0% (both inclusive) by central laboratory analysis 6. BMI ≤ 40.0 kg/m² 7. Ability and willingness to adhere to the protocol including performance of self measured plasma glucose (SMPG) profiles according to the protocol
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E.4 | Principal exclusion criteria |
1. Use within the last 3 months prior to Visit 1 of: GLP-1 receptor agonist (exenatide, liraglutide), rosiglitazone, DPP-IV inhibitors, α-glucosidase-inhibitors 2. Anticipated change in concomitant medication known to interfere significantly with glucose metabolism, such as systemic corticosteroids, beta-blockers, MAO inhibitors 3. Local off-label use of any concomitant medication, including OADs to be continued in the trial 4. Cardiovascular disease, within the last 6 months prior to Visit 1, defined as: stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty. 5. Uncontrolled treated/untreated severe hypertension (systolic blood pressure ≥180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure ≥ 100 mmHg). 6. Impaired liver function, defined as ALAT ≥ 2.5 times upper limit of normal (one retest analysed at the central laboratory within a week of receipt of the result is permitted with the result of the last sample being conclusive). 7. Impaired renal function defined as serum-creatinine ≥ 125 µmol/L (≥ 1.4 mg/dL) for males and ≥ 110 µmol/L (≥ 1.3 mg/dL) for females or according to local label for metformin use. One re-test within a week of receipt of the result is permitted with the result of the last sample being conclusive. 8. Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months 9. Proliferative retinopathy or maculopathy requiring treatment according to the Investigator 10. Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements 11. Cancer and medical history of cancer hereof (except basal cell skin cancer and squamous cell skin cancer) 12. 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 13. Mental incapacity, psychiatric disorder, unwillingness or language barriers precluding adequate understanding or co-operation, including subjects not able to read or write 14. 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. 15. Known or suspected allergy to any of the trial products or related products 16. Receipt of any investigational drug within one month prior to Visit 1. 17. Donation of blood or participation in other trials within one month prior to Visit 1 18. Known or suspected abuse of alcohol, narcotics or illicit drugs
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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 (analysed by central laboratory) |
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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 | No |
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.8.3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
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 | 9 |