E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
The change from baseline in HbA1c after 14 weeks treatment |
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E.2.2 | Secondary objectives of the trial |
Key sencondary objectives are to assess whether the combination therapy (once daily) has improved tolerability to gastrointestinal (GI) side effects over metformin alone (twice daily), by comparing the composite endpoint of occurrence of treat to target response, defined HbA1c<7.0% and no occurence of moderate or severe metformin pre-specified GI side effects during 14 weeks treatment; and the occurrence of metformin pre-specified moderate or severe GI side effects during 14 weeks treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of T2DM prior to informed consent; 2. Male and female patients on diet and exercise regimen who are drug-naïve, defined as absence of any oral antidiabetic drugs (OAD) or any injectable antidiabetic therapies for at least 12 weeks prior to randomization; 3. HbA1c of >/=7.0% (53 mmol/mol) and </=10.0% (86 mmol/mol) at Visit 1 (screening); 4. Age>/=18 and </=80 years at visit 1(screening); 5. Body Mass Index(BMI)</= 45kg/m2 at vist 1 (screening); 6. Signed and dated written informed consent by date of Visit 1 in accordance with GCP and local legislation |
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E.4 | Principal exclusion criteria |
1.Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (13.3mmol/L) after an overnight fast during screening/placebo run-in and confirmed by a second measurement (Not on the same day);
2.Treatment with any oral antidiabetic drug or insulin within 12 weeks prior to randomization;
3. Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or TIA within 3 months prior to informed consent;
4. Indication of liver disease / Impaired hepatic function , defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or run-in phase 5. Impaired renal function, defined as eGFR<60 ml/min (MDRD formula) as determined during screening or run-in phase;
5. Impaired renal function, defined as eGFR<60 ml/min (MDRD formula) as determined during screening or run-in phase;
6. Bariatric surgery within the past two years and other gastrointestinal surgeries that induced chronic malaborption;
7. Medical history of Cancer(except for basal cell carcinoma) and/or treatment for cancer within the last 5 years;
8. Blood dyscrasia or any other disorders causing hemolysis or unstable Red Blood Cell (eg. malaria, babesiosis, hamolytic anemia);
9. Known history of pancreatitis and chronic pancreatitis;
10. Contraindications to moetformin according to the local label;
11. Treatment with anti-obesity drugs 3 months prior to informed consent or any otehr treatment at the time of screening (i.e. surgery, aggressive diet regimenm etc.) leading to unstable body weight;
12. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM;
13. Pre-menopausal women (last menstruation less than 1 year prior to informed consent) who:
a. are nursing or pregnant or
b. are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to contiune using this method throughout the study and do not agree to submit to periodic pregancy testing during parcipation in the trial or who do not agree to continue contraception for at least 30 days after the last dose of study drug. Acceptable methods of birth control include transdermal patch, intra-uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence and vasectomised partner.
14. Alcohol or drug abuse within 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drgu intake;
15. Participation in another trial with application of any investigational drug within 30 days prior to informed consent;
16. Any other clinical condition that would jeopardize patients safety while participating in this clinical trial according to investigator’s judgement; |
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E.5 End points |
E.5.1 | Primary end point(s) |
1: The change from baseline in Glycosylated Hemoglobin A1c (HbA1c) after 14 weeks treatment
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1: Composite endpoint of occurence of treat to target efficacy response, that is an HbA1c under treatment of <7.0% after 14 weeks of treatment, and no occurence of moderate or severe gastrointestinal (GI) side effects during 14 weeks of treatment
2: Change from baseline in fasting plasma glucose (FPG) after 14 weeks of treatment
3: Metformin pre-specified GI symptom intensity score assessed by investigators during 14 weeks of treatment
4: Metformin pre-specified GI symptom intensty score assessed by patients during 14 weeks of treatment
5: Composite endpoint of occurrence of treat to target efficacy response, that is an HbA1c under treatment of <6.5% after 14 weeks of treatment, and on occurence of moderate or severe metformin pre-specified GI side effects assessed by investigators
6: Occurrence of relative efficacy response (HbA1c lowering by at least 0.5% after 14 weeks of treatment)
7: Occurence of metformin pre-specified moderate to severe GI side effects assessed by investigators during 14 weeks of treatment
8: Occurrence of relative efficacy response (HbA1c lowering by at least 0.8% after 14 weeks of treatment)
9: Composite endponit of occurence of relative efficacy response(HbA1c lowering by at least 0.5% after 14 weeks of treatment) and no occurence of moderate and severe metformin pre-specified GI side effects assessed by the investigators during 14 weeks
10: Compostie endpoint of occurrence of relative efficacy response(HbA1c lowering by at least 0.8% after 14 weeks of treatment) and no occurrence of moderate and severe metformin pre-specified GI side effects assessed by investigators during 14 weeks
11: change from baseline in HbA1c by visit over time
12: change from baseline in body weight by visit over time
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: 14 weeks
2: 14 weeks
3: 14 weeks
4: 14 weeks
5: 14 weeks
6: 14 weeks
7: 14 weeks
8: 14 weeks
9: 14 weeks
10: 14 weeks
11: 14 weeks
12: 14 weeks
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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 | Yes |
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 | 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 | 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 | 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.8.2.4 | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
China |
Guatemala |
Hong Kong |
India |
Lebanon |
Mexico |
Peru |
Philippines |
Taiwan |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 18 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 18 |