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 |
Diabetes is a problem with the body that causes blood sugar levels to rise higher than normal. In type 2 diabetes the body does not use insulin properly. |
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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 | 18.0 |
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 primary objective of the current study is to investigate the safety and tolerability of a once daily oral dose of 20 mg, 80 mg or 240 mg BI 187004 as mono-therapy and 240 mg BI 187004 on a stable metformin background over 28 days in patients with type 2 diabetes mellitus. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the change from baseline in fasting plasma glucose after 28 days of treatment with 20 mg, 80 mg or 240 mg BI 187004 as mono-therapy and 240 mg BI 187004 on a stable metformin background |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or postmenopausal or hysterectomised female patients with diagnosis of T2DM before informed consent
2. To be eligible for Arm 1
a. Oral antidiabetic mono-therapy for the last 12 weeks prior to Informed Consent AND Glycosylated haemoglobin (HbA1c) >= 6.5% and <= 8.5% at Visit 1a
b. Therapy-naïve patients or no antidiabetic treatment within 4 weeks prior to Informed Consent AND HbA1c >= 7.0% and <= 9.5% at Visit 1a.
3. To be eligible for Arm 2:
a. Antidiabetic treatment with metformin with an unchanged daily dose for 12 weeks prior to Informed Consent AND patient´s willingness to keep this therapy stable during the course of the trial AND HbA1c >= 7.0% and <= 9.5% at Visit 1a
4. Age >=18 and <=80 years for female hysterectomised and male patients at Visit 1a
5. Age >=55 and <=80 years for female postmenopausal (defined by the absence of menses for at least 2 years) patients at Visit 1a
6. Body mass index (BMI) >= 28 and <= 40 kg/m2 at Visit 1a
7. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation |
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E.4 | Principal exclusion criteria |
1. Treatment with a non-oral antidiabetic therapy or with more than one oral antidiabetic medication within 12 weeks prior to visit 1a.
2. Fasted plasma glucose > 240 mg/dl (>13.3 mmol/l) on two consecutive days after screening (Visit 1a) confirmed by a fasted laboratory blood glucose test until first administration of the trial drug
3. Any laboratory value more than 3 times above upper limit normal (ULN) at screening (visit 1a) or any other laboratory value outside the reference range and clinically relevant in the investigator judgment
4. Any known clinically relevant concomitant diseases or chronic diseases other than type 2 diabetes, hyperlipidaemia or medically treated hypertension
5. Medical history of cancer or treatment for cancer in the last five years prior to the Visit 1a.
6. History of Cushing syndrome, Addison´s disease, congenital adrenal hyperplasia or polycystic ovary syndrome
7. Treatment with systemic, inhalatory or ophthalmologic steroids within 12 weeks prior to first administration of the trial drug.
8. Treatment compliance during the run-in period is outside the per protocol range defined range, between 80%-120% treatment compliance.
9. Use of any other concomitant medication within 5 half-lives before the first administration of the trial drug except for allowed co-medication.
10. Surgery or trauma with significant blood loss (more than 500 ml) within the last 3 months prior to informed consent or blood donation (more than 100 ml) within four weeks prior to first administration of study medication or planned during the trial
11. Any other medical condition that would interfere with trial participation based on investigator´s judgement or any on-going clinical condition that would jeopardize patient´s or site personnel´s safety or study compliance based on investigator judgement. Smoking habits interfering with hospitalization. Patients not willing to abstain from alcoholic beverages during inpatient visits
12. Male patients not willing to use adequate contraception (sexual abstinence, condom use plus another form of contraception e.g. spermicide, oral contraceptive taken by female partner, sterilisation, intrauterine device) during the whole study period from the time of the first intake of study drug until three months after the last intake
13. Prior to Visit 3, plasma cortisol levels higher than 83 nmol/l, in the morning,
after treatment with 2 mg of oral Dexamethasone (Dexamethasone suppression test).
14. Prior to Visit 3, plasma cortisol peak levels after CRH iv injection of <377 nmol/L OR ACTH peak levels after CRH iv injection of <4.4 pmol/L. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1: The number (%) of patients with drug- related adverse events
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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: Change from baseline in fasting plasma glucose (FPG) after 28 days of treatment
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 3 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 12 |