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 | 10049746 |
E.1.2 | Term | Insulin-requiring 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 |
Primary: To demonstrate the superiority of insulin glargine over insulin NPH on the change in HbA1c from baseline to the end of the treatment period.
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E.2.2 | Secondary objectives of the trial |
Main Secondary: To compare between treatment groups: • Plasma glucose (fasting, nocturnal) over time, • Changes from baseline in HbA1c over time, • Percentage of patients who reach the target of HbA1c <7% and <6.5%, • Use of prandial insulin as rescue medication at month 6 • Incidence and rate of hypoglycemia (symptomatic diurnal and nocturnal, asymptomatic and severe), • Daily dose of insulin, • Change in body weight from baseline, • Evolution of 8-point plasma-glucose (PG) profiles, • Overall safety, • Patient reported outcomes (treatment satisfaction). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria • Aged from 30 to 70 years inclusively • Insulin-naïve type 2 diabetes mellitus • Type 2 diabetes mellitus diagnosed for at least 1 year • Treated with at least one OAD (Metformin [daily dose of at least 1000mg], Sulfonylurea, glinides or alpha-glucosidase inhibitor) at stable dose for at least 3 months. • HbA1c > or = 7.0% and < or = 10,5% • BMI < 40 kg/m2 • Ability and willingness to perform plasma glucose monitoring using the sponsor-provided glucose meter and patient diary at home • Informed consent obtained in writing at enrolment into the study • Willingness and ability to comply with the study protocol
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E.4 | Principal exclusion criteria |
Exclusion criteria: • Treatment with GLP-1 agonists or with DPP-IV inhibitors in the 3 months prior to study entry • Treatment with TZD as monotherapy • Diabetes mellitus other than Type 2 (e.g. secondary to pancreatic disorders, drugs or chemical agents intake • Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study (an optic fundus examination should have been performed within the 2 years prior to study entry) • Impaired renal function: serum creatinine ≥ 1.5 mg/dL (≥ 133µmol/L) or ≥ 1.4 mg/dL (≥ 124 µmol/L) in men and women, respectively • History of sensitivity to the study drugs or to drugs with a similar chemical structure • Impaired hepatic function (ALT and/or AST > 3 x upper limit of normal range) • Pregnant or lactating women; Women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method. Medically approved contraceptive method is defined as contraceptive pill, contraceptive patch, hormonal implant, injectible contraceptive and intrauterine device. Local approved method is defined as condom and cap with intravaginal spermicide. States that do not require contraception are tubal ligation, hysterectomy, oophorectomy, infertility and vasectomized partner. Women that have reach menopause are defined as no menstrual period for 12 consecutive months and no other biological or physiological cause can be identified. • Treatment with systemic corticosteroids within the 3 months prior to study entry or likelihood of requiring treatments during the study which are not permitted. • Treatment with an investigational product in the 30 days prior to visit 1 • Alcohol or drug abuse in the last year • Presence of any condition (medical, psychological, social or geographical), current or anticipated that the Investigator feels would compromise the patient’s safety or limit the patient successful participation in the study (including night shift worker)
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in HbA1c from baseline to end of study treatment in ITT population Data collected for the assessment of efficacy and safety criteria: At specific time points: • HbA1c recorded at baseline, weeks 12, 24 and 36 • Self-monitored fasting plasma glucose assessment over 6 consecutive days before baseline, weeks 12, 24 and 36 • During the week before baseline, at 12, 24 and 36 weeks, patients will do a 8-point plasma glucose profile twice a week (at their convenience): immediately before and 2 hours after breakfast, lunch and dinner, at bedtime and at 3:00 a.m before insulin initiation and 5 to 6 hours after insulin injection during the treatment period. One or both of these nocturnal values will be used for insulin titration. • Need of additional a prandial insulin at month 6 • Body weight measured at baseline, weeks 4, 8, 12, 24 and 36 • Daily doses of insulin at each visit, • Lipid profile at baseline and week 36 , • Patient reported outcomes: Treatment satisfaction will be assessed using the DTSQs at baseline, weeks 12, 24 and 36 and the DTSQc at week 36. • Vital signs at each visit,
All across the study: • Episodes of hypoglycemia. • Adverse events |
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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 | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |