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Trial record 31 of 726 for:    Area Under Curve AND Bioavailability

Relative Bioavailability of Olodaterol and Fluconazole

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ClinicalTrials.gov Identifier: NCT01153724
Recruitment Status : Completed
First Posted : June 30, 2010
Results First Posted : June 10, 2014
Last Update Posted : June 10, 2014
Sponsor:
Information provided by:
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Healthy
Pulmonary Disease, Chronic Obstructive
Interventions Drug: BI 1744
Drug: Fluconazole
Enrollment 35
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. 35 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 capsule Fluconazole 400 milligram once daily, both for 14 days (with a loading dose of 800 milligram on the first day).
Period Title: Treatment Period 1
Started 35
Completed 34
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Period Title: Treatment Period 2
Started 34
Completed 32
Not Completed 2
Reason Not Completed
Adverse Event             1
Other reason not defined above             1
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. 35 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 capsule Fluconazole 400 milligram once daily, both for 14 days (with a loading dose of 800 milligram on the first day).
Overall Number of Baseline Participants 35
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 35 participants
32.0  (9.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants
Female
18
  51.4%
Male
17
  48.6%
1.Primary Outcome
Title Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)
Hide Description AUC0-6,ss represents the area under the concentration curve of olodaterol in plasma from 0 to time t=6 hours 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 Fluconazole
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 Fluconazole 400mg capsule administered orally once daily for 14 days.
Overall Number of Participants Analyzed 24 28
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Picogram*hours/milliliter
19.659
(13.6%)
22.271
(13.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olodaterol, Olodaterol Plus Fluconazole
Comments Ratio Olodaterol plus Fluconazole and Olodaterol
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 0.0101
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 113.29
Confidence Interval (2-Sided) 90%
105.893 to 121.197
Parameter Dispersion
Type: Standard Deviation
Value: 13.6
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 (a metabolite of olodaterol) 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
Arm/Group Title Olodaterol Olodaterol Plus Fluconazole
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 Fluconazole 400mg capsule administered orally once daily for 14 days.
Overall Number of Participants Analyzed 33 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Picogram/milliliter
Olodaterol (N=30;32)
5.336
(15.5%)
5.805
(15.5%)
Olodaterol glucuronide (N=33;32)
4.211
(19.4%)
3.621
(19.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olodaterol, Olodaterol Plus Fluconazole
Comments Ratio Olodaterol plus Fluconazole and Olodaterol for the category Olodaterol
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 0.0009
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 108.78
Confidence Interval (2-Sided) 90%
101.590 to 116.487
Parameter Dispersion
Type: Standard Deviation
Value: 15.5
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 Fluconazole
Comments Ratio Olodaterol plus Fluconazole and Olodaterol for the category Olodaterol glucuronide
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 0.0711
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
Estimated Value 85.98
Confidence Interval (2-Sided) 90%
79.277 to 93.253
Parameter Dispersion
Type: Standard Deviation
Value: 19.4
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
Arm/Group Title Olodaterol Olodaterol Plus Fluconazole
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 Fluconazole 400mg capsule administered orally once daily for 14 days.
Overall Number of Participants Analyzed 33 32
Median (Full Range)
Unit of Measure: Hours
Olodaterol (N=30;32)
0.250
(0.117 to 1.00)
0.250
(0.0830 to 1.00)
Olodaterol glucuronide (N=33;32)
2.00
(0.0330 to 22.9)
2.03
(0.0330 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
Arm/Group Title Olodaterol Olodaterol Plus Fluconazole
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 Fluconazole 400mg capsule administered orally once daily for 14 days.
Overall Number of Participants Analyzed 32 32
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: percentage of olodaterol
5.63
(39.8%)
6.45
(33.1%)
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 excreted in urine from 0 to time t=24 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
Arm/Group Title Olodaterol Olodaterol Plus Fluconazole
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 Fluconazole 400mg capsule 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
563.459
(33.5%)
647.004
(33.5%)
Olodaterol glucuronide
465.946
(26.5%)
347.030
(26.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olodaterol, Olodaterol Plus Fluconazole
Comments Ratio Olodaterol plus Fluconazole and Olodaterol for the category Olodaterol
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 0.1539
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 114.83
Confidence Interval (2-Sided) 90%
99.940 to 131.932
Parameter Dispersion
Type: Standard Deviation
Value: 33.5
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 Fluconazole
Comments Ratio Olodaterol plus Fluconazole and Olodaterol for the category Olodaterol glucuronide
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 0.8574
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 74.48
Confidence Interval (2-Sided) 90%
66.619 to 83.266
Parameter Dispersion
Type: Standard Deviation
Value: 1.068
Estimation Comments The standard deviation is actually the geometric coefficient of variation
6.Secondary Outcome
Title Area Under Curve From 0 to 12 Hours at Steady State (AUC0-12,ss)
Hide Description AUC0-12,ss represents the area under the concentration curve of olodaterol glucuronide in plasma from 0 to time t=12 at steady state, where t is defined as the latest timepoint 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
Arm/Group Title Olodaterol Olodaterol Plus Fluconazole
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 Fluconazole 400mg capsule administered orally once daily for 14 days.
Overall Number of Participants Analyzed 27 29
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Picogram*hours/milliliter
33.389
(14.6%)
24.735
(14.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Olodaterol, Olodaterol Plus Fluconazole
Comments Ratio Olodaterol plus Fluconazole and Olodaterol
Type of Statistical Test Non-Inferiority or Equivalence
Comments Relative bioavailability
Statistical Test of Hypothesis P-Value 0.9646
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 74.08
Confidence Interval (2-Sided) 90%
69.105 to 79.418
Parameter Dispersion
Type: Standard Deviation
Value: 14.6
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 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 had taken at least 1 dose of trial medication.
Arm/Group Title Olodaterol Olodaterol Plus Fluconazole
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 Fluconazole 400mg capsule administered orally once daily for 14 days.
Overall Number of Participants Analyzed 35 34
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 Fluconazole
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 Fluconazole 400mg capsule administered orally once daily for 14 days.
Overall Number of Participants Analyzed 35 34
Measure Type: Number
Unit of Measure: participants
Good 35 30
Satisfactory 0 3
Not satisfactory 0 0
Bad 0 1
Not assessable 0 0
Time Frame First administration of trial medication until 6 days after last administration of trial medication
Adverse Event Reporting Description Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
 
Arm/Group Title Olodaterol Olodaterol Plus Fluconazole
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 Fluconazole 400mg capsule administered orally once daily for 14 days.
All-Cause Mortality
Olodaterol Olodaterol Plus Fluconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Olodaterol Olodaterol Plus Fluconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)   0/34 (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 Fluconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   2/35 (5.71%)   18/34 (52.94%) 
Gastrointestinal disorders     
Constipation  1  1/35 (2.86%)  2/34 (5.88%) 
Paraesthesia oral  1  0/35 (0.00%)  2/34 (5.88%) 
General disorders     
Fatigue  1  0/35 (0.00%)  7/34 (20.59%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/35 (0.00%)  9/34 (26.47%) 
Nervous system disorders     
Headache  1  1/35 (2.86%)  5/34 (14.71%) 
Psychiatric disorders     
Sleep disorder  1  0/35 (0.00%)  3/34 (8.82%) 
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: NCT01153724     History of Changes
Other Study ID Numbers: 1222.48
2010-018528-18 ( EudraCT Number: EudraCT )
First Submitted: June 29, 2010
First Posted: June 30, 2010
Results First Submitted: March 28, 2014
Results First Posted: June 10, 2014
Last Update Posted: June 10, 2014