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 | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
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 objective of the study is to investigate the efficacy, safety, and tolerability of linagliptin 5 milligrams (mg) once a day (q.d.) compared to an initial combination of linagliptin 5 mg and metformin immediate release (IR) in a total daily dose of 1500 to 2000 mg/day for 24 weeks in newly diagnosed, treatment-naïve patients with Type 2 Diabetes Mellitus (T2DM) |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female patients, 18 years of age or older at Visit 1 (Screen), with newly diagnosed (less than 12 months prior to Screen) T2DM.
2. Patients who are treatment-naïve, defined as absence of any oral antidiabetic therapy, injectable GLP-1 agonist/analogue, or insulin, and uncontrolled for the 12 weeks prior to randomisation.
3. Patients must have an HbA1c between 8.5% [69 millimoles per mole (mmol/mol)] and 12.0% (108 mmol/mol) at Visit 1 (Screen).
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E.4 | Principal exclusion criteria |
1. Acute coronary syndrome (non-ST Elevation Myocardial Infarction (STEMI), STEMI, and unstable angina pectoris), stroke or transient ischemic attack within 3 months prior to informed consent.
2.Indication of liver disease determined during Screen and/or Run-In Period, defined by a serum level above 3 times the upper limit of normal (ULN) in any of the following: alanine aminotransferase [ALT or called serum glutamic pyruvic transaminase (SGPT)], aspartate aminotransferase [AST or serum glutamic oxaloacetic transaminase (SGOT)], or alkaline phosphatase. Gilbert-Meulengracht syndrome (also known as conjugated hyperbilirubinemia, constitutional hepatic dysfunction, or familial nonhemolytic jaundice) will be permitted.
3.Impaired renal function, defined as calculated creatinine clearance of less than 60 milliters per minute (< 60 mL/min), by the Cockcroft-Gault Equation, as determined during Screen and/or Run-In Period.
4.Bariatric, gastric bypass, and other gastrointestinal surgeries (including all types of gastric banding and/or LapBand) within the past two years.
5.Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years.
6.Medical history of pancreatitis.
7.Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells (e.g., malaria, babesiosis, haemolytic anaemia).
8.Any contraindication to metformin IR and/or linagliptin therapies, according to local labels.
9.Treatment with anti-obesity drugs, including over-the-counter drugs such as Alli(orlistat), 3 months prior to informed consent or any other treatment at the time of screening (i.e., surgery, aggressive diet regimen, etc.) leading to unstable body weight.
10.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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in HbA1c |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 24 weeks of treatment |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in fasting plasma glucose
2. Change from baseline in HbA1c |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
ad 1. After 24 weeks of treatment
ad 2. by visit over time |
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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 | 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 | 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 | 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 | 11 |
E.8.5 | The trial involves multiple Member States | No |
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 |
India |
Israel |
Malaysia |
Mexico |
Philippines |
Russian Federation |
Slovakia |
Sri Lanka |
Thailand |
Ukraine |
United States |
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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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The end of the trial is defined as 'last patient out', i.e. last scheduled visit completed by last patient. |
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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 | 1 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 5 |