Clinical trial NCT00558909: 4 Weeks Treatment of Type II Diabetic Patients With BI 44847
Official title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 4 Weeks Treatment With Three Selected Oral Doses of BI 44847 as Tablet in Female and Male Patients With Type 2 Diabetes.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-11-15
Enrollment: 80
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: The primary objective of the current study is to investigate the safety and tolerability of BI 44847 in male and female patients with type 2 diabetes following oral administration of repeated doses of 100 mg b.i.d, 400 mg b.i.d. and 800 mg b.i.d. over 28 days.

A secondary objective is the exploration of the pharmacokinetics and pharmacodynamics of BI 44847 after multiple dosing, including assessment of steady state.


Eligibility criteria: Inclusion Criteria:

* Male and postmenopausal or hysterectomised female patients with proven diagnosis of type 2 diabetes mellitus treated with diet and exercise only or with one or 2 oral hypoglycaemic agent other than glitazones. In case of 2 oral hypoglycaemic agents, at least one of these may be taken at no more than 50% of its maximum dose;
* Age = \> 21 and Age = \<70 years (female hysterectomised and male patients);
* Age = \>55 and Age = \<70 years (female postmenopausal patients);
* BMI = \>18.5 and BMI = \<40 kg/m2 (Body Mass Index);
* Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.

Exclusion Criteria:

* Treatment with insulin, glitazones, or more than one oral hypoglycaemic agent (except if 2 agents and at least one of them not taken at more than 50% of maximum dose);
* Fasted blood glucose \> 240 mg/dl on two consecutive days during wash-out; HbA1c \> 8.5 % at screening;
* Clinically relevant concomitant diseases other than type 2 diabetes, hyperlipidaemia and medically treated hypertension;
* History of relevant allergy/hypersensitivity;
* Marked baseline prolongation of QT/QTc interval;
* History of additional risk factors for TdP;
* Any laboratory value outside the reference range and the clinical relevance is not acceptable in the opinion of the investigator, or the value is more than 3 times higher than the upper limit of the reference range;
* Concomitant medication except for acetylsalicylic acid, statins, antihypertensives (diuretics not allowed), beta-blockers for BPH and occasional use of paracetamol (doses of no more than 1000 mg; no more than 2000 mg per day; no more than 2 days per week);
* Change of drug dosing of allowed co-medication \< the last 6 weeks; Intake of any medication \< 5 half-lives of the respective drug prior to first administration of study medication or during the trial, except allowed co-medication;
* Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval (based on the knowledge at the time of patient inclusion) \< 10 days prior to first administration of study medication or during the trial;
* Use of grapefruit (or its juice) \< 10 days prior to first administration of study medication or during the trial;
* Participation in another trial with an investigational drug \< two months prior to first administration of study medication or during the trial; Smoker;
* Inability to refrain from smoking on specified trial days; Alcohol abuse;
* Drug abuse;
* Blood donation;
* Excessive physical activity;
* Male patients not using adequate contraception;
* Women of childbearing potential, positive pregnancy test or lactating

Primary outcomes:
measure: Weight and waist circumference - change from baseline
timeFrame: Day 28 (Hour = 647:30)
measure: Frequency of patients with maximal increase from baseline QTcF and QTcB interval
timeFrame: 4 weeks
measure: Frequency of patients with possible clinically significant abnormalities
timeFrame: 4 weeks
measure: Micturition total frequency - change from baseline
timeFrame: Day 28
measure: Global tolerability - number of patients by category
timeFrame: 4 weeks
Secondary outcomes:
measure: Cmax (maximum concentration of the analyte in plasma)
timeFrame: Day 1
measure: Tmax (time from dosing to maximum concentration)
timeFrame: Day 1
measure: t1/2 (terminal half-life of the analyte in plasma)
timeFrame: Day 1
measure: λz (terminal rate constant in plasma)
timeFrame: Day 1
measure: C12,1 (concentration of analyte in plasma at 12 hours post-drug administration after administration of the first dose)
timeFrame: Day 1
measure: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point within the first dosing interval)
timeFrame: Day 1
measure: AUC0-12 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 h after administration of the first dose)
timeFrame: Day 1
measure: Ae0-12 (amount of analyte that is eliminated in urine over the time interval 0 h to 12 h)
timeFrame: Day 1
measure: fe0-12 (fraction of analyte excreted unchanged in urine from time points 0 h to 12 h)
timeFrame: Day 1
measure: CLR (renal clearance of the analyte in plasma after extravascular administration - based on 0 - 12 hour data)
timeFrame: Day 1
measure: CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
timeFrame: Day 1
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
timeFrame: Day 1
measure: Cmax,ss (maximum concentration of the analyte in plasma at steady state over a uniform dosing interval)
timeFrame: Day 28
measure: Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)
timeFrame: Day 28
measure: Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N)
timeFrame: Day 28
measure: Cpre,ss (predose concentration of the analyte in plasma at steady state immediately before administration of the last dose)
timeFrame: Day 28
measure: C12,ss (concentration of analyte in plasma at 12 hours post-drug administration at steady state)
timeFrame: Day 28
measure: tmax,ss (time from dosing to maximum concentration at steady state)
timeFrame: Day 28
measure: tmin,ss (time from dosing to minimum concentration during a dosing interval)
timeFrame: Day 28
measure: AUC0-tz,ss (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point within the last dosing interval)
timeFrame: Day 28
measure: AUC0-12,ss (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 h at steady-state)
timeFrame: Day 28
measure: MRTpo,ss (mean residence time of the analyte in the body after 56 administrations (b.i.d.) at steady state)
timeFrame: Day 28
measure: CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)
timeFrame: Day 28
measure: Vz/F,ss (apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state)
timeFrame: Day 28
measure: Ae0-12,ss (amount of analyte that is eliminated in urine at steady state over the time interval 0 to 12 h)
timeFrame: Day 28
measure: fe0-12,ss (fraction of analyte excreted unchanged in urine at steady state over the time interval 0 to 12 h)
timeFrame: Day 28
measure: CLR,ss (renal clearance of the analyte at steady state - based on 0 - 12 hour data)
timeFrame: Day 28
measure: RA,Cmax based on Cmax
timeFrame: following 55 doses (bid)
measure: RA,AUC based on AUCτ
timeFrame: following 55 doses (bid)
measure: Predose concentrations of the analyte in plasma
timeFrame: 5 minutes before drug administration on days 2,3,4,7,14,21,26,27,28 and 29
measure: Change from baseline in UGE, AE0-24
timeFrame: Day 27
measure: Change from baseline in weighted MDG, AUEC0-24
timeFrame: Day 27
measure: Epre-corrected AUEC0-5 following OGTT
timeFrame: Day 28
measure: Cavg (average concentration)
timeFrame: day 28
measure: PTF (peak trough fluctuation).
timeFrame: day 28
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: 1224.4.49002 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1224.4.49003 Boehringer Ingelheim Investigational Site
city: Neuss
country: Germany
facility: 1224.4.49001 Boehringer Ingelheim Investigational Site
city: Zuidlaren
country: Netherlands
facility: 1224.4.31001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: