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 investigate if IAsp added step-wise (1-2-3) in a Basic regimen (according to the largest meal, and titrated based mainly on pre-meal SMPG) is equivalent to IAsp added step-wise (1-2-3) in an Advanced regimen (according to the largest prandial increment, and titrated based mainly on post-meal SMPG) as measured by HbA1c after 36 weeks of treatment in subjects with type 2 diabetes treated with once daily IDet in combination with OAD(s). |
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E.2.2 | Secondary objectives of the trial |
To compare the proportion of subjects achieving HbA1c levels <7.0% at 11, 23 and 36 weeks with IAsp at the largest meal (Basic Basal Plus regimen) vs. IAsp at the meal with the largest prandial increment (Advanced Basal Plus regimen), both as add-on to IDet and OADs●To compare the FPG at 36 weeks●Compare the average prandial increments●Compare the % of subjects with post prandial PG readings above 8.0 mmol/L or 11.1 mmol/L ●Compare the safety profile as measured by occurrence of AEs●Compare the safety profile as measured by changes in lab. safety parameters, physical examination, and vital signs●Compare the relative incidence of hypoglycaemia●Other objectives●Compare changes in body weight, BMI, waist/hip circumference●Evaluate the distribution of bolus injections by meal and number of boluses●Evaluate insulin doses●Evaluate the average daily bolus insulin doses●Assess the distribution of subjects on 1, 2 or 3 boluses of IAsp●Assess and compare Patient Reported Outcomes. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Signed informed consent obtained before any trial-related activities (Trial related activities are any procedure that would not have been performed during the normal management of the subject) 2.Type 2 diabetes mellitus ≥ 6 months (at visit 2) 3.Age ≥ 18 years (at visit 1) 4.HbA1c ≥ 7.5% and < 10.0% (at Visit 1) 5.BMI < 40.0 kg/m2 6.Basal insulin treatment (NPH once or twice daily, insulin glargine once daily or IDet once daily) for at least 3 months (at Visit 2) 7.Treatment with 1-3 OADs a.Metformin ≥ 1500 mg daily or highest tolerable dose b.± SU ≥ 50% of maximum dose (in accordance with local labelling) c.± Pioglitazone or Rosiglitazone in accordance with local labelling 8.Able and willing to perform SMPG testing as per protocol 9.Able and willing to eat 3 main meals each day during the trial 10.Able and willing to adhere to the therapeutic regimens
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E.4 | Principal exclusion criteria |
1.Known or suspected allergy to trial product(s) or related products 2.Previous participation in any trial for the last 3 months 3.Previous participation in this trial defined as past inclusion at visit 2 4.Women of childbearing potential who are pregnant, breast-feeding or intend to become pregnant within the next 50 weeks or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice). UK: Adequate contraceptive measures are defined as sterilisation, intra-uterine device, oral contraceptives or consistent use of barrier methods 5.Use of more than 1 U/kg of basal insulin daily (at Visit 1) 6.Treatment with α-glucosidase inhibitors (at Visit 1) 7.Treatment with GLP-1 mimetics or DPP-IV inhibitors (at Visit 1) 8.Active proliferative retinopathy or maculopathy requiring treatment within 6 mnths prior to screening 9.Cardiac disease defined as NYHA class III or IV, unstable angina and/or myocardial infarction within 6 months prior to screening 10.Uncontrolled hypertension (treated or untreated) as judged by the Investigator 11.Any disease or condition (such as renal, hepatic or cardiac) that according to the judgement of the Investigator makes the subject unsuitable for participation in the trial 12.Recurrent (> 2 episodes) hypoglycaemia with PG < 3.1 mmol/L (55.8 mg/dL) within the last month or hypoglycaemic unawareness as judged by the investigator 13.Use of concomitant medication which may alter glucose metabolism including but not limited to: systemic (or inhaled) glucocorticoids or non-selective beta-blockers 14.Substance abuse including abuse of anabolic steroids 15.Mental incapacity or language barrier precluding adequate understanding and/or cooperation 16.Any condition that the investigator and/or Sponsor consider a potential obstacle to trial participation and/or data analysis 17.Treatment with other insulin than those described in inclusion criteria no. 6
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E.5 End points |
E.5.1 | Primary end point(s) |
Key Efficacy Endpoints •HbA1c (cf. Section 8.2.1) •1-, 4-, 6- and 7-point SMPG profiles (cf. Section 8.2.4) •FPG (laboratory analysis)(cf. Section 8.2.3)
Key safety Endpoints •AEs (cf. Section 8.3.1) •Hypoglycaemic episodes (cf. Section 8.3.2) •Haematology (cf. Section 8.3.5) •Biochemistry (cf. Section 8.3.6) •Lipids (cf. Section 8.3.3) •Physical examination (cf. Section 8.3.8) •Vital signs (cf. Section 8.3.7) •CV risk markers (cf. section 8.3.4)
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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) | No |
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) | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | |
E.8.9.1 | In the Member State concerned months | 15 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 15 |