Relative Bioavailability of of Olodaterol and Ketoconazole

Relative Bioavailability of 10 mcg Olodaterol (Solution for Inhalation Administered With the Respimat) at Steady State Alone or in Combination With Multiple Doses of 400 mg q.d. Ketoconazole (Tablet) in Healthy Male and Female Volunteers (an Open Label, Fixed Sequence, Phase I Study)

This clinical trial is intended to investigate a possible effect of the p-gp inhibitor ketoconazole on the bioavailability of olodaterol

Study Overview

• Status: Completed
• Conditions: Healthy; Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: BI 1744; Drug: Ketoconazole

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Ingelheim, Germany
    • 1222.47.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria Healthy male and female volunteers

Exclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 1744 10 mcg; solution for oral inhalation	Drug: BI 1744; 10 mcg solution for oral inhalation; Drug: Ketoconazole; 400 mg tablet
Experimental: Ketoconazole 400 mg; tablet	Drug: BI 1744; 10 mcg solution for oral inhalation; Drug: Ketoconazole; 400 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Curve From 0 to 1 Hour at Steady State (AUC0-1,ss)	AUC0-1,ss represents the area under the concentration curve of olodaterol in plasma from 0 to time t=1 hour at steady state, where t is defined as the latest time-point where at least 2/3 of the subjects in both treatment periods reveal quantifiable plasma concentrations of olodaterol. The geometric mean is actually the adjusted geometric mean. The geometric coefficient of variation (gCV) is the intra-individual gCV.	Day 8 of period 1 and day 14 of period 2
Maximum Concentration at Steady State (Cmax,ss)	Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state. The geometric mean is actually the adjusted geometric mean. The geometric coefficient of variation (gCV) is the intra-individual gCV.	Day 8 of period 1 and day 14 of period 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)	tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.	Day 8 of period 1 and day 14 of period 2
Fraction of Urine Excretion From 0 to 24 Hours at Steady State (fe0-24,ss)	fe0-24,ss represents the fraction of olodaterol eliminated in urine from time point 0 to 24 hours after administration at steady state.	Day 8 of period 1 and day 14 of period 2
Amount of the Analyte Excreted in Urine From 0 to 24 Hours at Steady State (Ae0-24,ss)	Ae0-24,ss represents the amount of olodaterol and olodaterol glucuronide that is eliminated in urine from the time 0 to 24h after administration at steady state. The geometric mean is actually the adjusted geometric mean. The geometric coefficient of variation (gCV) is the intra-individual gCV.	Day 8 of period 1 and day 14 of period 2
Area Under Curve From 0 to 8 Hours at Steady State (AUC0-8,ss)	AUC0-8,ss represents the area under the concentration curve of olodaterol glucuronide in plasma from 0 to time t=8 at steady state, where t is defined as the latest time-point where at least 2/3 of the subjects in both treatment periods reveal quantifiable plasma concentrations of the analyte. The geometric mean is actually the adjusted geometric mean. The geometric coefficient of variation (gCV) is the intra-individual gCV.	Day 8 of period 1 and day 14 of period 2
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG	Clinical relevant abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as treatment-induced Adverse Events.	First administration of trial medication until 6 days after last administration of trial medication
Assessment of Tolerability by the Investigator	The investigator assessed tolerability based on adverse events and the laboratory evaluation at the end-of-trial examination. The investigator classified the overall tolerability according to the categories 'good', 'satisfactory', 'not satisfactory', and 'bad'.	End of period 1 and end of period 2

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: June 29, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (Estimate): June 30, 2010

Study Record Updates

• Last Update Posted (Estimate): April 30, 2014
• Last Update Submitted That Met QC Criteria: March 28, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Ketoconazole
• Other Study ID Numbers: 1222.47; 2010-018527-25 (EudraCT Number: EudraCT)