Bioavailability of BI 10773 and Pioglitazone in Healthy Male Volunteers

• ClinicalTrials.gov Identifier: NCT02276365
• Recruitment Status: Completed
• First Posted: October 28, 2014
• Last Update Posted: October 28, 2014
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: October 27, 2014
• First Posted Date: October 28, 2014
• Last Update Posted Date: October 28, 2014
• Study Start Date: June 2009
• Actual Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2014)

• AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) [ Time Frame: up to 10 days ]
• Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) [ Time Frame: up to 10 days ]

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 27, 2014)

• Abnormal findings in physical examination [ Time Frame: Baseline and up to 10 days after last study drug administration ]
• Changes from baseline in vital signs (Blood pressure, pulse rate) [ Time Frame: Baseline and up to 10 days after last study drug administration ]
• Changes from baseline in 12-lead ECG (electrocardiogram) [ Time Frame: Baseline and up to 10 days after last study drug administration ]
• Changes in clinical laboratory tests [ Time Frame: Baseline and up to 10 days after last study drug administration ]
• Incidence of adverse events [ Time Frame: up to 35 days ]
• Assessment of tolerability by investigator on a 4-point scale [ Time Frame: Within 3-10 days after last study drug administration ]
• C24,N (concentration of analyte in plasma at 24 hours post-drug administration after administration of the Nth dose) [ Time Frame: up to 10 days ]
• λz,ss (terminal half-life of the analyte in plasma) [ Time Frame: up to 10 days ]
• t½,ss (terminal half-life of the analyte in plasma at steady state) [ Time Frame: up to 10 days ]
• tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ) [ Time Frame: up to 10 days ]
• MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration) [ Time Frame: up to 10 days ]
• CL/F,ss (apparent clearance of the analyte in the plasma after extravascular administration at steady state) [ Time Frame: up to 10 days ]
• Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) [ Time Frame: up to 10 days ]
• Aet1-t2,ss (amount of analyte eliminated in urine at steady state over a uniform dosing interval τ) [ Time Frame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing ]
• fet1-t2,ss (fraction of analyte excreted unchanged in urine at steady state over a uniform dosing interval τ) [ Time Frame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing ]
• CLR,ss (renal clearance of the analyte at steady state) [ Time Frame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing ]
• UGE0-24 (Urinary glucose excretion of the analyte in urine over the time interval from time zero to 24 h) [ Time Frame: 1 hour pre-dose, 0-2, 2-4, 4-8, 8-12, 12-24 hours after last dosing ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Bioavailability of BI 10773 and Pioglitazone in Healthy Male Volunteers
• Official Title: Relative Bioavailability of Both BI 10773 50 mg and Pioglitazone 45 mg After Co-administration Compared to BI 10773 and Pioglitazone Alone in Healthy Male Volunteers (an Open-label, Randomised, Crossover, Clinical Phase I Study)
• Brief Summary: The objective of the study was to investigate whether there is a drug-drug interaction between BI 10773 and pioglitazone when co-administered as multiple oral doses. Therefore, the relative bioavailabilities of BI 10773 and pioglitazone were determined when both drugs were given in combination compared with BI 10773 and pioglitazone given alone.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Healthy

Intervention

• Drug: BI 10773
• Drug: Pioglitazone

Study Arms

• Experimental: Sequence ABC
  1. Treatment A: 50 mg BI 10773 once daily from day 1 to 5
  2. Treatment B: 50 mg BI 10773 and 45 mg pioglitazone once daily from day 1 to 7
  3. Treatment C: 45 mg pioglitazone once daily from day 1 to 7 after 7 days wash-out
  Interventions:

  • Drug: BI 10773
  • Drug: Pioglitazone
• Experimental: Sequence CAB
  1. Treatment C: 45 mg pioglitazone once daily from day 1 to 7
  2. Treatment A: 50 mg BI 10773 once daily from day 1 to 5 after 7 days wash-out
  3. Treatment B: 50 mg BI 10773 and 45 mg pioglitazone once daily from day 1 to 7
  Interventions:

  • Drug: BI 10773
  • Drug: Pioglitazone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 27, 2014): 20
• Original Actual Enrollment: Same as current
• Study Completion Date: Not Provided
• Actual Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy males according to the following criteria:

  • Based upon a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead ECG (electrocardiogram), clinical laboratory tests
• Age 18 to 50 years (incl.)
• BMI 18.5 to 29.9 kg/m2 (incl.)
• Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation

Exclusion Criteria:

• Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
• Any evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs with a long half-life (more than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoker (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (more than 30 g/day)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within one week prior to administration or during the trial)
• ALT (Alanine transaminase) outside the normal range or any other laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of trial site
• Galactose or lactose intolerance, galactose or glucose malabsorption

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT02276365
• Other Study ID Numbers: 1245.17
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Boehringer Ingelheim
• Study Sponsor: Boehringer Ingelheim
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Boehringer Ingelheim
• Verification Date: May 2014