Safety and Tolerability, Efficacy, Pharmacokinetic and Pharmacodynamic Study of Three Doses of BI 187004 Over 28 Days in Patients With Type 2 Diabetes Mellitus With and Without Metformin

Study Overview
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Brief Summary
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Assess the safety and tolerability of once daily oral doses of BI 187004 in patients with type 2 diabetes mellitus without oral antidiabetic treatment and in patients on a stable metformin background treatment over 28 days. Assess the effect on fasting plasma glucose after 28 days of treatment and to investigate the pharmacokinetics and pharmacodynamics of BI 187004.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel Groups Study to Investigate the Safety and Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of Three BI 187004 Doses Given Once Daily as Mono-therapy and of the Highest BI 187004 Dose Given Once Daily as Add on Treatment to Metformin Over 28 Days in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: BI 187004
* Drug: Placebo
* Drug: BI 187004
* Drug: BI 187004
* Drug: BI 187004


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or postmenopausal or hysterectomised female patients with diagnosis of Type 2 Diabetes Mellitus (T2DM) before informed consent To be eligible for Arm 1 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 Therapy-naïve patients or no antidiabetic treatment within 4 weeks prior to Informed Consent AND HbA1c >= 7.0% and <= 9.5% at Visit 1a. 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 Age >=18 and <=80 years for female hysterectomised and male patients at Visit 1a Age >=55 and <=80 years for female postmenopausal (defined by the absence of menses for at least 2 years) patients at Visit 1a Body mass index (BMI) >= 28 and <= 40 kg/m2 at Visit 1a Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation Exclusion criteria: Treatment with a non-oral antidiabetic therapy or with more than one oral antidiabetic medication within 12 weeks prior to visit 1a. 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 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 Any known clinically relevant concomitant diseases or chronic diseases other than type 2 diabetes, hyperlipidaemia or medically treated hypertension Medical history of cancer or treatment for cancer in the last five years prior to the Visit 1a. History of Cushing syndrome, Addison´s disease, congenital adrenal hyperplasia or polycystic ovary syndrome Treatment with systemic, inhalatory or ophthalmologic steroids within 12 weeks prior to first administration of the trial drug. Treatment compliance during the run-in period is outside the per protocol range defined range, between 80%-120% treatment compliance. Use of any other concomitant medication within 5 half-lives before the first administration of the trial drug except for allowed co-medication. 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 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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 187004 low dose mono QD<br>patient to receive one tablet containing low dose of BI 187004 or matching placebo | Drug: Placebo<br>* BI 187004 low dose matching placebo once daily<br>Drug: BI 187004<br>* BI 187004 low dose once daily<br>|
| Experimental: BI 187004 medium dose mono QD<br>patient to receive one tablet containing medium dose mg of BI 187004 or matching placebo | Drug: Placebo<br>* BI 187004 medium dose matching placebo once daily<br>Drug: BI 187004<br>* BI 187004 medium dose once daily<br>|
| Experimental: BI 187004 high dose mono QD<br>patient to receive one tablet containing high dose of BI 187004 or matching placebo | Drug: Placebo<br>* BI 187004 high dose matching placebo once daily<br>Drug: BI 187004<br>* BI 187004 high dose once daily<br>|
| Experimental: BI 187004 high dose QD add on<br>patient to receive one tablet containing high dose of BI 187004 or matching placebo add on to metformin background dose | Drug: Placebo<br>* BI 187004 high dose matching placebo once daily add on to background metformin<br>Drug: BI 187004<br>* BI 187004 high dose once daily add on to background metformin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients with drug- related adverse events |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in fasting plasma glucose (FPG) after 28 days of treatment |  | 4 weeks |