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Trial record 32 of 729 for:    Area Under Curve AND Bioavailability

Relative Bioavailability of of Olodaterol and Ketoconazole

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ClinicalTrials.gov Identifier: NCT01153711
Recruitment Status : Completed
First Posted : June 30, 2010
Results First Posted : April 30, 2014
Last Update Posted : April 30, 2014
Sponsor:
Information provided by:
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Healthy
Pulmonary Disease, Chronic Obstructive
Interventions Drug: BI 1744
Drug: Ketoconazole
Enrollment 32
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Overall Study
Hide Arm/Group Description Total number of patients treated in the study. This was an open-label, fixed sequence, phase I trial in healthy volunteers. 32 subjects received in period 1 Olodaterol 10 microgram delivered by Respimat inhaler once daily for 8 days and in period 2 Olodaterol 10 microgram delivered by Respimat inhaler once daily plus 1 tablet Ketoconazole 400mg once daily, both for 14 days.
Period Title: Overall Study
Started 32
Completed 32
Not Completed 0
Arm/Group Title Overall Study
Hide Arm/Group Description Total number of patients treated in the study. This was an open-label, fixed sequence, phase I trial in healthy volunteers. 32 subjects received in period 1 Olodaterol 10 microgram delivered by Respimat inhaler once daily for 8 days and in period 2 Olodaterol 10 microgram delivered by Respimat inhaler once daily plus 1 tablet Ketoconazole 400mg once daily, both for 14 days.
Overall Number of Baseline Participants 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants
38.5  (7.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Female
12
  37.5%
Male
20
  62.5%
1.Primary Outcome
Title Area Under Curve From 0 to 1 Hour at Steady State (AUC0-1,ss)
Hide Description 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.
Time Frame Day 8 of period 1 and day 14 of period 2
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) analysis set includes all evaluable subjects in the treated set providing at least 1 observation for at least 1 PK endpoint without important protocol violations.
Arm/Group Title Olodaterol Olodaterol Plus Ketoconazole
Hide Arm/Group Description:
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 14 days plus Ketoconazole 400mg tablet administered orally once daily for 14 days.
Overall Number of Participants Analyzed 24 31
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Picogram*hours/milliliter
2.512
(16.4%)
4.231
(16.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olodaterol, Olodaterol Plus Ketoconazole
Comments Ratio Olodaterol plus Ketoconazole and Olodaterol
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 1.0000
Comments P-value for ratio outside interval 0.8-1.25
Method ANOVA
Comments Adjusted geometric mean ratio
Method of Estimation Estimation Parameter Adjusted geometric mean ratio
Estimated Value 168.4
Confidence Interval (2-Sided) 90%
155.5 to 182.4
Parameter Dispersion
Type: Standard Deviation
Value: 16.4
Estimation Comments The standard deviation is actually the geometric coefficient of variation
2.Primary Outcome
Title Maximum Concentration at Steady State (Cmax,ss)
Hide Description 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.
Time Frame Day 8 of period 1 and day 14 of period 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set with evaluable data for this endpoint.
Arm/Group Title Olodaterol Olodaterol Plus Ketoconazole
Hide Arm/Group Description:
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 14 days plus Ketoconazole 400mg tablet administered orally once daily for 14 days.
Overall Number of Participants Analyzed 32 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Picogram/milliliter
Olodaterol (N=26;31)
3.113
(16.8%)
5.169
(16.8%)
Olodaterol glucuronide (N=32;32)
5.125
(14.7%)
5.465
(14.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olodaterol, Olodaterol Plus Ketoconazole
Comments Ratio Olodaterol plus Ketoconazole and Olodaterol for the category Olodaterol
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 1.0000
Comments P-value for ratio outside 0.8-1.25
Method ANOVA
Comments Adjusted geometric mean ratio
Method of Estimation Estimation Parameter Adjusted geometric mean ratio
Estimated Value 166.1
Confidence Interval (2-Sided) 90%
153.6 to 179.6
Parameter Dispersion
Type: Standard Deviation
Value: 16.8
Estimation Comments The standard deviation is actually the geometric coefficient of variation
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Olodaterol, Olodaterol Plus Ketoconazole
Comments Ratio Olodaterol plus Ketoconazole and Olodaterol for the category Olodaterol glucuronide
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 0.0001
Comments P-value for ratio outside 0.8-1.25
Method ANOVA
Comments Adjusted geometric mean ratio
Method of Estimation Estimation Parameter Adjusted geometric mean ratio
Estimated Value 106.63
Confidence Interval (2-Sided) 90%
100.211 to 113.463
Parameter Dispersion
Type: Standard Deviation
Value: 14.7
Estimation Comments The standard deviation is actually the geometric coefficient of variation
3.Secondary Outcome
Title Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)
Hide Description tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.
Time Frame Day 8 of period 1 and day 14 of period 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set with evaluable data for this endpoint.
Arm/Group Title Olodaterol Olodaterol Plus Ketoconazole
Hide Arm/Group Description:
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 14 days plus Ketoconazole 400mg tablet administered orally once daily for 14 days.
Overall Number of Participants Analyzed 32 32
Median (Full Range)
Unit of Measure: Hours
Olodaterol (N=26;31)
0.250
(0.0830 to 0.750)
0.333
(0.167 to 0.750)
Olodaterol glucuronide (N=32;32)
4.00
(1.00 to 12.0)
3.01
(1.00 to 23.0)
4.Secondary Outcome
Title Fraction of Urine Excretion From 0 to 24 Hours at Steady State (fe0-24,ss)
Hide Description fe0-24,ss represents the fraction of olodaterol eliminated in urine from time point 0 to 24 hours after administration at steady state.
Time Frame Day 8 of period 1 and day 14 of period 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set with evaluable data for this endpoint.
Arm/Group Title Olodaterol Olodaterol Plus Ketoconazole
Hide Arm/Group Description:
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 14 days plus Ketoconazole 400mg tablet administered orally once daily for 14 days.
Overall Number of Participants Analyzed 32 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Percentage
4.29
(35.2%)
6.19
(35.9%)
5.Secondary Outcome
Title Amount of the Analyte Excreted in Urine From 0 to 24 Hours at Steady State (Ae0-24,ss)
Hide Description 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.
Time Frame Day 8 of period 1 and day 14 of period 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set with evaluable data for this endpoint.
Arm/Group Title Olodaterol Olodaterol Plus Ketoconazole
Hide Arm/Group Description:
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 14 days plus Ketoconazole 400mg tablet administered orally once daily for 14 days.
Overall Number of Participants Analyzed 32 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng
Olodaterol
428.972
(17.8%)
618.716
(17.8%)
Olodaterol glucuronide
445.266
(18.9%)
591.620
(18.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olodaterol, Olodaterol Plus Ketoconazole
Comments Ratio Olodaterol plus Ketoconazole and Olodaterol for the category Olodaterol
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 0.9986
Comments P-value for ratio outside 0.8-1.25
Method ANOVA
Comments Adjusted geometric mean ratio
Method of Estimation Estimation Parameter Adjusted geometric mean ratio
Estimated Value 144.23
Confidence Interval (2-Sided) 90%
133.853 to 155.417
Parameter Dispersion
Type: Standard Deviation
Value: 17.8
Estimation Comments The standard deviation is actually the geometric coefficient of variation
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Olodaterol, Olodaterol Plus Ketoconazole
Comments Ratio Olodaterol plus Ketoconazole and Olodaterol for the category Olodaterol glucuronide
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 0.8991
Comments P-value for ratio outside 0.8-1.25
Method ANOVA
Comments Adjusted geometric mean ratio
Method of Estimation Estimation Parameter Adjusted geometric mean ratio
Estimated Value 132.87
Confidence Interval (2-Sided) 90%
122.732 to 143.843
Parameter Dispersion
Type: Standard Deviation
Value: 18.9
Estimation Comments The standard deviation is actually the geometric coefficient of variation
6.Secondary Outcome
Title Area Under Curve From 0 to 8 Hours at Steady State (AUC0-8,ss)
Hide Description 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.
Time Frame Day 8 of period 1 and day 14 of period 2
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set with evaluable data for this endpoint.
Arm/Group Title Olodaterol Olodaterol Plus Ketoconazole
Hide Arm/Group Description:
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 14 days plus Ketoconazole 400mg tablet administered orally once daily for 14 days.
Overall Number of Participants Analyzed 25 30
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Picogram*hours/milliliter
27.868
(17.9%)
28.076
(17.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olodaterol, Olodaterol Plus Ketoconazole
Comments Ratio Olodaterol plus Ketoconazole and Olodaterol
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 0.0001
Comments P-value for ratio outside interval 0.8-1.25
Method ANOVA
Comments Adjusted geometric mean ratio
Method of Estimation Estimation Parameter Adjusted geometric mean ratio
Estimated Value 100.75
Confidence Interval (2-Sided) 90%
92.534 to 109.692
Parameter Dispersion
Type: Standard Deviation
Value: 17.9
Estimation Comments The standard deviation is actually the geometric coefficient of variation
7.Secondary Outcome
Title Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
Hide Description 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.
Time Frame First administration of trial medication until 6 days after last administration of trial medication
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set (TS) - Treated set includes all patients who were dispensed trial medication and were documented to have taken at least 1 dose of investigational treatment.
Arm/Group Title Olodaterol Olodaterol Plus Ketoconazole
Hide Arm/Group Description:
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 14 days plus Ketoconazole 400mg tablet administered orally once daily for 14 days.
Overall Number of Participants Analyzed 32 32
Measure Type: Number
Unit of Measure: participants
0 0
8.Secondary Outcome
Title Assessment of Tolerability by the Investigator
Hide Description 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'.
Time Frame End of period 1 and end of period 2
Hide Outcome Measure Data
Hide Analysis Population Description
TS
Arm/Group Title Olodaterol Olodaterol Plus Ketoconazole
Hide Arm/Group Description:
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 14 days plus Ketoconazole 400mg tablet administered orally once daily for 14 days.
Overall Number of Participants Analyzed 32 32
Measure Type: Number
Unit of Measure: participants
Good 32 32
Satisfactory 0 0
Not satisfactory 0 0
Bad 0 0
Not assessable 0 0
Time Frame First administration of trial medication until 6 days after last administration of trial medication
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Olodaterol Olodaterol Plus Ketoconazole
Hide Arm/Group Description Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days. Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 14 days plus Ketoconazole 400mg tablet administered orally once daily for 14 days.
All-Cause Mortality
Olodaterol Olodaterol Plus Ketoconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Olodaterol Olodaterol Plus Ketoconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   0/32 (0.00%)   0/32 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Olodaterol Olodaterol Plus Ketoconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   5/32 (15.63%)   9/32 (28.13%) 
Gastrointestinal disorders     
Diarrhoea  1  0/32 (0.00%)  2/32 (6.25%) 
Dry mouth  1  1/32 (3.13%)  2/32 (6.25%) 
Nausea  1  0/32 (0.00%)  5/32 (15.63%) 
Immune system disorders     
Allergy to arthropod bite  1  2/32 (6.25%)  0/32 (0.00%) 
Nervous system disorders     
Headache  1  2/32 (6.25%)  1/32 (3.13%) 
Tremor  1  0/32 (0.00%)  2/32 (6.25%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01153711     History of Changes
Other Study ID Numbers: 1222.47
2010-018527-25 ( EudraCT Number: EudraCT )
First Submitted: June 29, 2010
First Posted: June 30, 2010
Results First Submitted: March 28, 2014
Results First Posted: April 30, 2014
Last Update Posted: April 30, 2014