| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Patients with type 2 diabetes
• with insufficient glycaemic control (HbA1c ≥ 7.5 to < 11 % at Visit 2)
• with very poor glycaemic control (HbA1c ≥ 11 %)
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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 |
|
| 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 |
The main objective of the randomised part of the trial: Efficacy and safety of BI 1356 + metformin compared to BI 1356 or metformin alone given for 24 weeks to drug naïve or previously treated (4 weeks wash-out, 2 weeks placebo run-in) type 2 diabetic patients with insufficient glycaemic control.
For the open-label part of the study the objective is to estimate the efficacy and safety of BI 1356 and metformin in type II diabetic patients with very poor glycaemic control for 24 weeks.
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| E.2.2 | Secondary objectives of the trial |
Secondary endpoints for both the randomised and open-label parts of the trial are:
• The occurrence of a treat to target efficacy response, that is an HbA1c
under treatment of < 7.0 % after 24 weeks of treatment
• The occurrence of treat to target efficacy response, that is an HbA1c
under treatment of < 6.5 % after 24 weeks of treatment
• Occurrence of relative efficacy response (HbA1c lowering by at least 0.5 %
after 24 weeks of treatment)
• HbA1c reduction from baseline by visit over time
• The change from baseline in fasting plasma glucose (FPG, biomarker)
after 24 weeks of treatment
• The change from baseline in fasting plasma glucose (FPG, biomarker)
by visit over time
• Meal Tolerance Test (MTT): two-hour postprandial glucose value (2hPPG)
at baseline, after 24 weeks of treatment and change from baseline to week 24
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
This trial will include 2 substudies:
Substudy: Pharmacogenetic sample taking
Substudy: Meal Tolerance Test
The MTT substudy will include additional measurements of biomarkers such as glucose (FPG, PPG), insulin, C-peptide, total and active GLP-1, DPP-4 inhibition (at baseline and 24 weeks) and PK measurement of BI 1356 plasma concentration.
|
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| E.3 | Principal inclusion criteria |
• Male and female patients with a diagnosis of type 2 diabetes mellitus, either
treatment drug naïve patients or previously treated patients with not more than
one oral antidiabetic drug. Antidiabetic therapy has to be unchanged for 10 weeks
prior to informed consent
• Diagnosis of type 2 diabetes prior to informed consent
• Glycosylated haemoglobin A1c (HbA1c) at Visit 1a (Screening):
For patients undergoing wash-out (pre-treated patients): HbA1c ≥ 7.0 to ≤ 10.5 %.
For naïve patients not undergoing wash-out: HbA1c ≥ 7.5 to < 11.0%
• Glycosylated haemoglobin A1c (HbA1c) ≥ 7.5 to < 11.0% at Visit 2 (Start of Run-in)
• Patients with very poor glycaemic control [HbA1c ≥ 11 %, determined by
examination at Visit 1a (naïve patients) or at Visit 2 (naïve and pre-treated
patients)] will be eligible to participate in an additional open-label study arm
• Age ≥ 18 and ≤ 80 years at Visit 1a (Screening)
• BMI (Body Mass Index) ≤ 40 kg/m2 at Visit 1a (Screening)
• Signed and dated written informed consent by date of Visit 1a in accordance with
GCP and local legislation
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|
| E.4 | Principal exclusion criteria |
• Myocardial infarction, stroke or TIA within 6 months prior to informed consent
• Impaired hepatic function, defined by serum levels of either ALT (SGPT), AST
(SGOT), or alkaline phosphatase (AP) above 3 x upper limit of normal (ULN) as
determined at Visit 1a
• Known hypersensitivity or allergy to verum or its excipients or metformin or placebo
• Treatment with rosiglitazone or pioglitazone within 3 months prior to informed
consent
• Treatment with a GLP-1 analogue (e.g. exenatide) within 3 months prior to
informed consent
• Treatment with insulin within 3 months prior to informed consent
• Treatment with anti-obesity drugs (e.g. sibutramine, orlistat, rimonabant) within
3 months prior to informed consent
• Alcohol abuse within the 3 months prior to informed consent that would interfere
with trial participation or drug abuse
• Participation in another trial with an investigational drug within 2 months prior to
informed consent
• Pre-menopausal women (last menstruation ≤ 1 year prior to informed consent)
who are nursing or pregnant, or are of child-bearing potential and are not
practicing an acceptable method of birth control, or do not plan to continue using
this method throughout the study and do not agree to submit to periodic
pregnancy testing during participation in the trial. Acceptable methods of birth
control include transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral,
implantable or injectable contraceptives, sexual abstinence and vasectomised
partner
• Current treatment with systemic steroids at time of informed consent or change in
dosage of thyroid hormones within 6 weeks prior to informed consent
• Renal failure or renal impairment at Visit 1a (screening) with an eGFR < 60 ml/min
• Gastric bypass
• Dehydration by clinical judgement of the investigator
• Unstable or acute congestive heart failure
• Acute or chronic metabolic acidosis (present in patient history)
• Hereditary galactose intolerance
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint in this study is the change from baseline in HbA1c after 24 weeks of treatment (for both the randomised and open-label parts of the trial). |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | 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 |
| additional open-label arm |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| 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 |
|
| 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
|
End of the trial is last visit of last subject undergoing the trial.
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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