Trial to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Oral Doses of BI135585 XX Administered as Tablet and as Solution in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01146886
First received: June 14, 2010
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

The purpose of the study is to investigate the safety, tolerability, pharmacokinetics incl. dose proportionality, and pharmacodynamics of BI 135585 XX (Part 1), as well as the relative bioavailability of two different immediate release tablet formulations versus oral solution (Part 2)


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Placebo to BI 135585
Drug: BI 135585
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: A Randomised, Double-blind, Placebo-controlled Trial to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of 10 mg to 1200 mg of BI 135585 XX Administered as a Solution to Healthy Male Volunteers (Trial Part 1), Followed by an Open, Randomised, Single-dose, Intra-individual Bioavailability Comparison of 200 mg BI 135585 XX as Tablet and as Solution (Trial Part 2)

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change from baseline in Physical examination (occurrence of findings) [ Time Frame: up to 14 days post treatment ] [ Designated as safety issue: No ]
  • Change from baseline in Vital signs (blood pressure [BP], pulse rate [PR], respiratory rate [RR]) [ Time Frame: up to 14 days post treatment ] [ Designated as safety issue: No ]
  • Change from baseline in 12-lead ECG with special attention to QTc prolongation [ Time Frame: up to 14 days post treatment ] [ Designated as safety issue: No ]
  • Cardiopulmonary monitoring resulting in clinically relevant findings [ Time Frame: up to 14 days post treatment ] [ Designated as safety issue: No ]
  • Change from baseline in Clinical laboratory parameters including hormones of the HPA axis and thyroid gland [ Time Frame: up to 14 days post treatment ] [ Designated as safety issue: No ]
  • Number of patients with Adverse events (AE) [ Time Frame: up to 14 days post treatment ] [ Designated as safety issue: No ]
  • Assessment of tolerability by the investigator [ Time Frame: up to 14 days post treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • (5α-THF + 5β-THF)/THE ratio as an indicator of 11β-HSD1 inhibition [ Time Frame: up to 24h ] [ 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 time of the last quantifiable data point) [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • tmax (time from dosing to maximum measured concentration) [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • %AUCtz-∞ (percentage of the AUC0-∞ that was obtained by extrapolation) [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • λz (terminal rate constant in plasma) [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • t1/2 (terminal half-life of the analyte in plasma) [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • MRToral (mean residence time of the analyte in the body after oral administration) [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • CL/F (total/apparent clearance of the analyte in plasma after extravascular administration) [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • Aet1-t2 (amount of analyte eliminated in urine from timepoint t1 to timepoint t2) SRD part only [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • fet1-t2 (fraction of analyte eliminated in urine from timepoint t1 to timepoint t2) SRD part only [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • CLR,t1-t2 (renal clearance of the analyte from timepoint t1 to timepoint t2) SRD part only[ [ Time Frame: up to 72 hours post treatment ] [ Designated as safety issue: No ]
  • UFF/UFE ratio as an indicator of 11β-HSD2 inhibition [ Time Frame: up to 24h ] [ Designated as safety issue: No ]
  • Total urinary corticosteroids (5α-THF + 5β-THF + THE + UFF + UFE) as an indicator of the activation of the HPA axis [ Time Frame: up to 24h ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: June 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 135585
1 single dose per subject as oral solution in Part 1, or 3 single doses per subject as oral solution and 2 different tablet formulations in Part 2
Drug: BI 135585
Part 1 - oral doses given to approximately 9 parallel groups of 8 subjects (6 on active and 2 on placebo) on Day 1; Part 2 - oral doses given to 12 subjects on Day 1
Placebo Comparator: Placebo to BI 135585
1 single dose per subject as oral solution in Part 1
Drug: Placebo to BI 135585
Part 1 - oral doses given to approximately 9 parallel groups of 8 subjects (6 on active and 2 on on placebo) on Day 1

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

- healthy male volunteers

  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: NCT01146886

Locations
Germany
1283.1.1 Boehringer Ingelheim Investigational Site
Biberach, 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: NCT01146886     History of Changes
Other Study ID Numbers: 1283.1, 2010-018856-28
Study First Received: June 14, 2010
Last Updated: October 31, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014