Trial Outcomes & Findings for Relative Bioavailability of Olodaterol and Fluconazole (NCT NCT01153724)
NCT ID: NCT01153724
Last Updated: 2014-06-10
Results Overview
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.
COMPLETED
PHASE1
35 participants
Day 8 of period 1 and day 14 of period 2
2014-06-10
Participant Flow
Participant milestones
| Measure |
Overall Study
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).
|
|---|---|
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Treatment Period 1
STARTED
|
35
|
|
Treatment Period 1
COMPLETED
|
34
|
|
Treatment Period 1
NOT COMPLETED
|
1
|
|
Treatment Period 2
STARTED
|
34
|
|
Treatment Period 2
COMPLETED
|
32
|
|
Treatment Period 2
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Overall Study
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).
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|---|---|
|
Treatment Period 1
Withdrawal by Subject
|
1
|
|
Treatment Period 2
Adverse Event
|
1
|
|
Treatment Period 2
Other reason not defined above
|
1
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Baseline Characteristics
Relative Bioavailability of Olodaterol and Fluconazole
Baseline characteristics by cohort
| Measure |
Overall Study
n=35 Participants
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).
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|---|---|
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Age, Continuous
|
32.0 years
STANDARD_DEVIATION 9.0 • n=99 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Day 8 of period 1 and day 14 of period 2Population: 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.
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.
Outcome measures
| Measure |
Olodaterol
n=24 Participants
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
|
Olodaterol Plus Fluconazole
n=28 Participants
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.
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|---|---|---|
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Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)
|
19.659 Picogram*hours/milliliter
Geometric Coefficient of Variation 13.6
|
22.271 Picogram*hours/milliliter
Geometric Coefficient of Variation 13.6
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PRIMARY outcome
Timeframe: Day 8 of period 1 and day 14 of period 2Population: PK analysis set
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.
Outcome measures
| Measure |
Olodaterol
n=33 Participants
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
|
Olodaterol Plus Fluconazole
n=32 Participants
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.
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|---|---|---|
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Maximum Concentration at Steady State (Cmax,ss)
Olodaterol (N=30;32)
|
5.336 Picogram/milliliter
Geometric Coefficient of Variation 15.5
|
5.805 Picogram/milliliter
Geometric Coefficient of Variation 15.5
|
|
Maximum Concentration at Steady State (Cmax,ss)
Olodaterol glucuronide (N=33;32)
|
4.211 Picogram/milliliter
Geometric Coefficient of Variation 19.4
|
3.621 Picogram/milliliter
Geometric Coefficient of Variation 19.4
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SECONDARY outcome
Timeframe: Day 8 of period 1 and day 14 of period 2Population: PK analysis set
tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.
Outcome measures
| Measure |
Olodaterol
n=33 Participants
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
|
Olodaterol Plus Fluconazole
n=32 Participants
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.
|
|---|---|---|
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Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)
Olodaterol (N=30;32)
|
0.250 Hours
Interval 0.117 to 1.0
|
0.250 Hours
Interval 0.083 to 1.0
|
|
Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)
Olodaterol glucuronide (N=33;32)
|
2.00 Hours
Interval 0.033 to 22.9
|
2.03 Hours
Interval 0.033 to 23.0
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SECONDARY outcome
Timeframe: Day 8 of period 1 and day 14 of period 2Population: PK analysis set
fe0-24,ss represents the fraction of olodaterol eliminated in urine from time point 0 to 24 hours after administration at steady state.
Outcome measures
| Measure |
Olodaterol
n=32 Participants
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
|
Olodaterol Plus Fluconazole
n=32 Participants
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.
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|---|---|---|
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Fraction of Urine Excretion From 0 to 24 Hours at Steady State (fe0-24,ss)
|
5.63 percentage of olodaterol
Geometric Coefficient of Variation 39.8
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6.45 percentage of olodaterol
Geometric Coefficient of Variation 33.1
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SECONDARY outcome
Timeframe: Day 8 of period 1 and day 14 of period 2Population: PK analysis set
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.
Outcome measures
| Measure |
Olodaterol
n=32 Participants
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
|
Olodaterol Plus Fluconazole
n=32 Participants
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.
|
|---|---|---|
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Amount of the Analyte Excreted in Urine From 0 to 24 Hours at Steady State (Ae0-24,ss)
Olodaterol
|
563.459 ng
Geometric Coefficient of Variation 33.5
|
647.004 ng
Geometric Coefficient of Variation 33.5
|
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Amount of the Analyte Excreted in Urine From 0 to 24 Hours at Steady State (Ae0-24,ss)
Olodaterol glucuronide
|
465.946 ng
Geometric Coefficient of Variation 26.5
|
347.030 ng
Geometric Coefficient of Variation 26.5
|
SECONDARY outcome
Timeframe: Day 8 of period 1 and day 14 of period 2Population: PK analysis set
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.
Outcome measures
| Measure |
Olodaterol
n=27 Participants
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
|
Olodaterol Plus Fluconazole
n=29 Participants
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.
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|---|---|---|
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Area Under Curve From 0 to 12 Hours at Steady State (AUC0-12,ss)
|
33.389 Picogram*hours/milliliter
Geometric Coefficient of Variation 14.6
|
24.735 Picogram*hours/milliliter
Geometric Coefficient of Variation 14.6
|
SECONDARY outcome
Timeframe: First administration of trial medication until 6 days after last administration of trial medicationPopulation: Treated set (TS) - Treated set includes all patients who had taken at least 1 dose of trial medication.
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.
Outcome measures
| Measure |
Olodaterol
n=35 Participants
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
|
Olodaterol Plus Fluconazole
n=34 Participants
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.
|
|---|---|---|
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Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: End of period 1 and end of period 2Population: TS
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'.
Outcome measures
| Measure |
Olodaterol
n=35 Participants
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
|
Olodaterol Plus Fluconazole
n=34 Participants
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.
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|---|---|---|
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Assessment of Tolerability by the Investigator
Good
|
35 participants
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30 participants
|
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Assessment of Tolerability by the Investigator
Satisfactory
|
0 participants
|
3 participants
|
|
Assessment of Tolerability by the Investigator
Not satisfactory
|
0 participants
|
0 participants
|
|
Assessment of Tolerability by the Investigator
Bad
|
0 participants
|
1 participants
|
|
Assessment of Tolerability by the Investigator
Not assessable
|
0 participants
|
0 participants
|
Adverse Events
Olodaterol
Olodaterol Plus Fluconazole
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Olodaterol
n=35 participants at risk
Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.
|
Olodaterol Plus Fluconazole
n=34 participants at risk
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.
|
|---|---|---|
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Gastrointestinal disorders
Constipation
|
2.9%
1/35 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
5.9%
2/34 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
|
Gastrointestinal disorders
Paraesthesia oral
|
0.00%
0/35 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
5.9%
2/34 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
|
General disorders
Fatigue
|
0.00%
0/35 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
20.6%
7/34 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/35 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
26.5%
9/34 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
|
Nervous system disorders
Headache
|
2.9%
1/35 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
14.7%
5/34 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/35 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
8.8%
3/34 • First administration of trial medication until 6 days after last administration of trial medication
Adverse events presented for treated set which includes all patients who had taken at least 1 dose of trial medication.
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place