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Pharmacokinetics, Safety and Tolerability of BI 671800 HEA Given Over 7 Days. A Randomised, Double Blind, Placebo Controlled Within Dose Groups Phase I Study in Healthy Male and Female Volunteers.

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01215773
First received: September 29, 2010
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

The main objectives of the multiple dose study are to investigate the safety, tolerability pharmacokinetics of BI 671800 HEA in healthy male and female volunteers following multiple oral administration of BI 671800


Condition Intervention Phase
Healthy
Drug: Placebo
Drug: BI 671800
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Pharmacokinetics, Safety and Tolerability of BI 671800 HEA Given 200 mg b.i.d. or 400 mg b.i.d. Over 7 Days. A Randomised, Double Blind, Placebo Controlled Within Dose Groups Phase I Study in Healthy Male and Female Volunteers.

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Vital signs (pulse rate (PR)) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Clinical laboratory test (clinical chemistry) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Clinical laboratory test (urinalysis) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Physical examination [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Vital signs (blood pressure (BP)) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • 12-lead ECG (electrocardiogram) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Clinical laboratory test (haematology) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Assessment of tolerability by investigator [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cmax (maximum plasma concentration of BI 671800 or BI 600957) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • tmax (time from dosing until maximum concentration of BI 671800 or BI 600957 is measured) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • AUC0-infinity (area under the plasma concentration-time curve of BI 671800 or BI 600957 from time of dosing extrapolated to infinity) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • AUCτ,1 (area under the plasma concentration-time curve of BI 671800 or BI 600957 for the complete dosing interval τ) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • AUC0-tz (area under the plasma concentration-time curve of BI 671800 or BI 600957 from time of dosing to time tz of last quantifiable concentration) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • Cmax,ss (maximum plasma concentration of BI 671800 or BI 600957 at steady state) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • tmax,ss (time from dosing until maximum concentration of BI 671800 or BI 600957 at steady state is measured) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • Cavg,ss (average measured plasma concentration of BI 671800 or BI 600957 at steady state) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • AUCτ,ss (area under the plasma concentration-time curve of BI 671800 or BI 600957 at steady state for the complete dosing interval τ) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • λz,ss (terminal rate constant of BI 671800 or BI 600957 in plasma at steady state) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • t1/2,ss (terminal half-life of BI 671800 or BI 600957 in plasma at steady state) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • MRTpo,ss (mean residence time of BI 671800 in the body at steady state after oral administration) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • CL/F,ss (apparent clearance of BI 671800 at steady state following oral administration) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • Vz/F,ss (apparent volume of distribution of BI 671800 during the terminal phase at steady state following oral administration) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • RAUCτ,ss,M/P (ratio of AUCτ,ss of the BI 600957 to AUCτ,ss of BI 671800) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • RCmax,ss,M/P (ratio of Cmax,ss of the BI 600957 to Cmax,ss of BI 671800) [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • accumulation ratios RA,Cmax [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • accumulation ratios RA,AUC [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • peak-trough fluctuation (PTF) of BI 671800 [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • peak-trough fluctuation (PTF) of BI 600957 [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]
  • linearity index (LI) of BI 671800 in plasma [ Time Frame: up to day 12 post treatment ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: October 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 671800 HEA medium dose
Tablet, oral administration with 240 mL of water for each treatment
Drug: BI 671800
Medium dose oral administration
Experimental: BI 671800 HEA high dose
2 Tablets, oral administration with 240 mL of water for each treatment
Drug: BI 671800
High dose oral administration
Placebo Comparator: Placebo
Matching to HEA 200 mg tablets, oral administration
Drug: Placebo
Matching to HEA 200 mg tablet, oral administration

  Eligibility

Ages Eligible for Study:   21 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  1. Healthy males and females according to the following criteria: Based upon a complete medical history, including physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
  2. Age 21 to 50 years (incl.)
  3. Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.)
  4. 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:

  1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
  2. Any evidence of a clinically relevant concomitant disease
  3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
  5. History of relevant orthostatic hypotension, fainting spells or blackouts
  6. Chronic or relevant acute infections
  7. History of relevant allergy or hypersensitivity (including allergy to drug or its excipients)
  8. Intake of drugs with a long half life (>24 h) within one month or less than 10 half-lives of the respective drug prior to first study drug administration
  9. Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
  10. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes daily)
  11. Alcohol abuse (average consumption of more than 20 g/day in females and 30 g/day in males) or positive alcohol test
  12. Drug abuse
  13. Blood donation (more than 100 mL within four weeks prior to day 1 of visit 2)
  14. Any laboratory value outside the reference range that is of clinical relevance, especially repeated Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl-transferase (GGT), Alkaline phosphatase (ALP) or total bilirubin above upper limit of normal (ULN) at screening and not resolved before dosing.
  15. Inability to comply with dietary regimen of trial site
  16. Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval within 10 days prior to administration or during the trial, and CYP2C8 substrates such as amiodarone, amodiaquine, paclitaxel, rosiglitazone, pioglitazone and repaglinide or CYP2C9 such as warfarin, tolbutamide, phenytoin, losartan, acenocoumarol within 1 month or six half lives (whichever is greater).
  17. Repeated demonstration of a QTc interval >450 ms, PR interval >230 ms or a QRS interval >120 ms; history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalaemia, family history of Long QT Syndrome)

    For female subjects of childbearing potential only:

  18. Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 2 months after study completion
  19. No adequate contraception during the study including three months before first dosing until 2 month after study completion, e.g. not any of the following: implants, injectables, combined hormonal contraceptives, intrauterine device, or surgical sterilisation (including hysterectomy). In addition to this, also a barrier method (e.g. condom) will be required, if the female is not surgically sterilised.
  20. Lactation
  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: NCT01215773

Locations
Germany
1268.59.1 Boehringer Ingelheim Investigational Site
Ingelheim, Germany
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: NCT01215773     History of Changes
Other Study ID Numbers: 1268.59, 2009-016369-27
Study First Received: September 29, 2010
Last Updated: October 31, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

ClinicalTrials.gov processed this record on November 25, 2014