4 Weeks Treatment of Type II Diabetic Patients With BI 44847

Diabetes Mellitus, Type 2 Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00558909
• Other study ID #: 1224.4
• Status: Completed
• Phase: Phase 1
• First received: August 30, 2007
• Last updated: April 30, 2014
• Start date: June 2007

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: BfArM (Bundesagentur fuer Arzneimittel und Medizinalprodukte)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 70 Years

Eligibility

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 Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• BI 44847

• placebo for BI 44847

Locations

Country	Name	City	State
Germany	1224.4.49002 Boehringer Ingelheim Investigational Site	Berlin
Germany	1224.4.49003 Boehringer Ingelheim Investigational Site	Mainz
Germany	1224.4.49001 Boehringer Ingelheim Investigational Site	Neuss
Netherlands	1224.4.31001 Boehringer Ingelheim Investigational Site	Zuidlaren

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight and waist circumference - change from baseline		Day 28 (Hour = 647:30)	No
Primary	Frequency of patients with maximal increase from baseline QTcF and QTcB interval		4 weeks	No
Primary	Frequency of patients with possible clinically significant abnormalities		4 weeks	No
Primary	Micturition total frequency - change from baseline		Day 28	No
Primary	Global tolerability - number of patients by category		4 weeks	No
Secondary	Cmax (maximum concentration of the analyte in plasma)		Day 1	No
Secondary	Tmax (time from dosing to maximum concentration)		Day 1	No
Secondary	t1/2 (terminal half-life of the analyte in plasma)		Day 1	No
Secondary	?z (terminal rate constant in plasma)		Day 1	No
Secondary	C12,1 (concentration of analyte in plasma at 12 hours post-drug administration after administration of the first dose)		Day 1	No
Secondary	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	No
Secondary	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	No
Secondary	Ae0-12 (amount of analyte that is eliminated in urine over the time interval 0 h to 12 h)		Day 1	No
Secondary	fe0-12 (fraction of analyte excreted unchanged in urine from time points 0 h to 12 h)		Day 1	No
Secondary	CLR (renal clearance of the analyte in plasma after extravascular administration - based on 0 - 12 hour data)		Day 1	No
Secondary	CL/F (apparent clearance of the analyte in the plasma after extravascular administration)		Day 1	No
Secondary	Vz/F (apparent volume of distribution during the terminal phase ?z following an extravascular dose)		Day 1	No
Secondary	Cmax,ss (maximum concentration of the analyte in plasma at steady state over a uniform dosing interval)		Day 28	No
Secondary	Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval)		Day 28	No
Secondary	Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N)		Day 28	No
Secondary	Cpre,ss (predose concentration of the analyte in plasma at steady state immediately before administration of the last dose)		Day 28	No
Secondary	C12,ss (concentration of analyte in plasma at 12 hours post-drug administration at steady state)		Day 28	No
Secondary	tmax,ss (time from dosing to maximum concentration at steady state)		Day 28	No
Secondary	tmin,ss (time from dosing to minimum concentration during a dosing interval)		Day 28	No
Secondary	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	No
Secondary	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	No
Secondary	MRTpo,ss (mean residence time of the analyte in the body after 56 administrations (b.i.d.) at steady state)		Day 28	No
Secondary	CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state)		Day 28	No
Secondary	Vz/F,ss (apparent volume of distribution during the terminal phase ?z following an extravascular dose at steady state)		Day 28	No
Secondary	Ae0-12,ss (amount of analyte that is eliminated in urine at steady state over the time interval 0 to 12 h)		Day 28	No
Secondary	fe0-12,ss (fraction of analyte excreted unchanged in urine at steady state over the time interval 0 to 12 h)		Day 28	No
Secondary	CLR,ss (renal clearance of the analyte at steady state - based on 0 - 12 hour data)		Day 28	No
Secondary	RA,Cmax based on Cmax		following 55 doses (bid)	No
Secondary	RA,AUC based on AUCt		following 55 doses (bid)	No
Secondary	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	No
Secondary	Change from baseline in UGE, AE0-24		Day 27	No
Secondary	Change from baseline in weighted MDG, AUEC0-24		Day 27	No
Secondary	Epre-corrected AUEC0-5 following OGTT		Day 28	No
Secondary	Cavg (average concentration)		day 28	No
Secondary	PTF (peak trough fluctuation).		day 28	No