4 Weeks Treatment of Type II Diabetic Patients With BI 44847

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.

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: BI 44847; Drug: placebo for BI 44847

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • 1224.4.49002 Boehringer Ingelheim Investigational Site
  • Mainz, Germany
    • 1224.4.49003 Boehringer Ingelheim Investigational Site
  • Neuss, Germany
    • 1224.4.49001 Boehringer Ingelheim Investigational Site
• Netherlands
  • Zuidlaren, Netherlands
    • 1224.4.31001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Weight and waist circumference - change from baseline	Day 28 (Hour = 647:30)
Frequency of patients with maximal increase from baseline QTcF and QTcB interval	4 weeks
Frequency of patients with possible clinically significant abnormalities	4 weeks
Micturition total frequency - change from baseline	Day 28
Global tolerability - number of patients by category	4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum concentration of the analyte in plasma)	Day 1
Tmax (time from dosing to maximum concentration)	Day 1
t1/2 (terminal half-life of the analyte in plasma)	Day 1
λz (terminal rate constant in plasma)	Day 1
C12,1 (concentration of analyte in plasma at 12 hours post-drug administration after administration of the first dose)	Day 1
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)	Day 1
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)	Day 1
Ae0-12 (amount of analyte that is eliminated in urine over the time interval 0 h to 12 h)	Day 1
fe0-12 (fraction of analyte excreted unchanged in urine from time points 0 h to 12 h)	Day 1
CLR (renal clearance of the analyte in plasma after extravascular administration - based on 0 - 12 hour data)	Day 1
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)	Day 1
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)	Day 1
Cmax,ss (maximum concentration of the analyte in plasma at steady state over a uniform dosing interval)	Day 28
Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)	Day 28
Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N)	Day 28
Cpre,ss (predose concentration of the analyte in plasma at steady state immediately before administration of the last dose)	Day 28
C12,ss (concentration of analyte in plasma at 12 hours post-drug administration at steady state)	Day 28
tmax,ss (time from dosing to maximum concentration at steady state)	Day 28
tmin,ss (time from dosing to minimum concentration during a dosing interval)	Day 28
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)	Day 28
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)	Day 28
MRTpo,ss (mean residence time of the analyte in the body after 56 administrations (b.i.d.) at steady state)	Day 28
CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)	Day 28
Vz/F,ss (apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state)	Day 28
Ae0-12,ss (amount of analyte that is eliminated in urine at steady state over the time interval 0 to 12 h)	Day 28
fe0-12,ss (fraction of analyte excreted unchanged in urine at steady state over the time interval 0 to 12 h)	Day 28
CLR,ss (renal clearance of the analyte at steady state - based on 0 - 12 hour data)	Day 28
RA,Cmax based on Cmax	following 55 doses (bid)
RA,AUC based on AUCτ	following 55 doses (bid)
Predose concentrations of the analyte in plasma	5 minutes before drug administration on days 2,3,4,7,14,21,26,27,28 and 29
Change from baseline in UGE, AE0-24	Day 27
Change from baseline in weighted MDG, AUEC0-24	Day 27
Epre-corrected AUEC0-5 following OGTT	Day 28
Cavg (average concentration)	day 28
PTF (peak trough fluctuation).	day 28

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: August 30, 2007
• First Submitted That Met QC Criteria: November 14, 2007
• First Posted (Estimate): November 15, 2007

Study Record Updates

• Last Update Posted (Estimate): May 1, 2014
• Last Update Submitted That Met QC Criteria: April 30, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 1224.4