4 Weeks Treatment of Type II Diabetic Patients With BI 44847

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00558909
First received: August 30, 2007
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: BI 44847
Drug: placebo for BI 44847
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Weight and waist circumference - change from baseline [ Time Frame: Day 28 (Hour = 647:30) ] [ Designated as safety issue: No ]
  • Frequency of patients with maximal increase from baseline QTcF and QTcB interval [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Frequency of patients with possible clinically significant abnormalities [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Micturition total frequency - change from baseline [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Global tolerability - number of patients by category [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cmax (maximum concentration of the analyte in plasma) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Tmax (time from dosing to maximum concentration) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • t1/2 (terminal half-life of the analyte in plasma) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • λz (terminal rate constant in plasma) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • C12,1 (concentration of analyte in plasma at 12 hours post-drug administration after administration of the first dose) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Ae0-12 (amount of analyte that is eliminated in urine over the time interval 0 h to 12 h) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • fe0-12 (fraction of analyte excreted unchanged in urine from time points 0 h to 12 h) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • CLR (renal clearance of the analyte in plasma after extravascular administration - based on 0 - 12 hour data) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • CL/F (apparent clearance of the analyte in the plasma after extravascular administration) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Cmax,ss (maximum concentration of the analyte in plasma at steady state over a uniform dosing interval) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Cpre,N (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose N) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Cpre,ss (predose concentration of the analyte in plasma at steady state immediately before administration of the last dose) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • C12,ss (concentration of analyte in plasma at 12 hours post-drug administration at steady state) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • tmax,ss (time from dosing to maximum concentration at steady state) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • tmin,ss (time from dosing to minimum concentration during a dosing interval) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • MRTpo,ss (mean residence time of the analyte in the body after 56 administrations (b.i.d.) at steady state) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Vz/F,ss (apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Ae0-12,ss (amount of analyte that is eliminated in urine at steady state over the time interval 0 to 12 h) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • fe0-12,ss (fraction of analyte excreted unchanged in urine at steady state over the time interval 0 to 12 h) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • CLR,ss (renal clearance of the analyte at steady state - based on 0 - 12 hour data) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • RA,Cmax based on Cmax [ Time Frame: following 55 doses (bid) ] [ Designated as safety issue: No ]
  • RA,AUC based on AUCτ [ Time Frame: following 55 doses (bid) ] [ Designated as safety issue: No ]
  • Predose concentrations of the analyte in plasma [ Time Frame: 5 minutes before drug administration on days 2,3,4,7,14,21,26,27,28 and 29 ] [ Designated as safety issue: No ]
  • Change from baseline in UGE, AE0-24 [ Time Frame: Day 27 ] [ Designated as safety issue: No ]
  • Change from baseline in weighted MDG, AUEC0-24 [ Time Frame: Day 27 ] [ Designated as safety issue: No ]
  • Epre-corrected AUEC0-5 following OGTT [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Cavg (average concentration) [ Time Frame: day 28 ] [ Designated as safety issue: No ]
  • PTF (peak trough fluctuation). [ Time Frame: day 28 ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: June 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558909

Locations
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, Germany
Netherlands
1224.4.31001 Boehringer Ingelheim Investigational Site
Zuidlaren, Netherlands
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00558909     History of Changes
Other Study ID Numbers: 1224.4
Study First Received: August 30, 2007
Last Updated: April 30, 2014
Health Authority: Germany: BfArM (Bundesagentur fuer Arzneimittel und Medizinalprodukte)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 26, 2014