Trial Outcomes & Findings for Relative Bioavailability of of Olodaterol and Ketoconazole (NCT NCT01153711)

NCT ID: NCT01153711

Last Updated: 2014-04-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

32 participants

Primary outcome timeframe

Day 8 of period 1 and day 14 of period 2

Results posted on

2014-04-30

Participant Flow

Participant milestones

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. 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 Study STARTED	32
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Relative Bioavailability of of Olodaterol and Ketoconazole

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study n=32 Participants 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.
Age, Continuous	38.5 years STANDARD_DEVIATION 7.2 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 8 of period 1 and day 14 of period 2

Population: 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.

AUC0-1,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.

Outcome measures

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 Ketoconazole n=31 Participants 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.
Area Under Curve From 0 to 1 Hour at Steady State (AUC0-1,ss)	2.512 Picogram*hours/milliliter Geometric Coefficient of Variation 16.4	4.231 Picogram*hours/milliliter Geometric Coefficient of Variation 16.4

PRIMARY outcome

Timeframe: Day 8 of period 1 and day 14 of period 2

Population: PK analysis set with evaluable data for this endpoint.

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.

Outcome measures

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 Ketoconazole n=32 Participants 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.
Maximum Concentration at Steady State (Cmax,ss) Olodaterol (N=26;31)	3.113 Picogram/milliliter Geometric Coefficient of Variation 16.8	5.169 Picogram/milliliter Geometric Coefficient of Variation 16.8
Maximum Concentration at Steady State (Cmax,ss) Olodaterol glucuronide (N=32;32)	5.125 Picogram/milliliter Geometric Coefficient of Variation 14.7	5.465 Picogram/milliliter Geometric Coefficient of Variation 14.7

SECONDARY outcome

Timeframe: Day 8 of period 1 and day 14 of period 2

Population: PK analysis set with evaluable data for this endpoint.

tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.

Outcome measures

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 Ketoconazole n=32 Participants 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.
Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) Olodaterol (N=26;31)	0.250 Hours Interval 0.083 to 0.75	0.333 Hours Interval 0.167 to 0.75
Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss) Olodaterol glucuronide (N=32;32)	4.00 Hours Interval 1.0 to 12.0	3.01 Hours Interval 1.0 to 23.0

SECONDARY outcome

Timeframe: Day 8 of period 1 and day 14 of period 2

Population: PK analysis set with evaluable data for this endpoint.

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

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 Ketoconazole n=32 Participants 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.
Fraction of Urine Excretion From 0 to 24 Hours at Steady State (fe0-24,ss)	4.29 Percentage Geometric Coefficient of Variation 35.2	6.19 Percentage Geometric Coefficient of Variation 35.9

SECONDARY outcome

Timeframe: Day 8 of period 1 and day 14 of period 2

Population: PK analysis set with evaluable data for this endpoint.

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.

Outcome measures

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 Ketoconazole n=32 Participants 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.
Amount of the Analyte Excreted in Urine From 0 to 24 Hours at Steady State (Ae0-24,ss) Olodaterol	428.972 ng Geometric Coefficient of Variation 17.8	618.716 ng Geometric Coefficient of Variation 17.8
Amount of the Analyte Excreted in Urine From 0 to 24 Hours at Steady State (Ae0-24,ss) Olodaterol glucuronide	445.266 ng Geometric Coefficient of Variation 18.9	591.620 ng Geometric Coefficient of Variation 18.9

SECONDARY outcome

Timeframe: Day 8 of period 1 and day 14 of period 2

Population: PK analysis set with evaluable data for this endpoint.

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.

Outcome measures

Outcome measures
Measure	Olodaterol n=25 Participants Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.	Olodaterol Plus Ketoconazole n=30 Participants 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.
Area Under Curve From 0 to 8 Hours at Steady State (AUC0-8,ss)	27.868 Picogram*hours/milliliter Geometric Coefficient of Variation 17.9	28.076 Picogram*hours/milliliter Geometric Coefficient of Variation 17.9

SECONDARY outcome

Timeframe: First administration of trial medication until 6 days after last administration of trial medication

Population: 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.

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.

Outcome measures

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 Ketoconazole n=32 Participants 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.
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 2

Population: 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

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 Ketoconazole n=32 Participants 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.
Assessment of Tolerability by the Investigator Bad	0 participants	0 participants
Assessment of Tolerability by the Investigator Good	32 participants	32 participants
Assessment of Tolerability by the Investigator Satisfactory	0 participants	0 participants
Assessment of Tolerability by the Investigator Not satisfactory	0 participants	0 participants
Assessment of Tolerability by the Investigator Not assessable	0 participants	0 participants

Adverse Events

Olodaterol

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Olodaterol Plus Ketoconazole

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Olodaterol n=32 participants at risk Oral inhalation of Olodaterol 10 microgram solution with Respimat A5 device once daily for 8 days.	Olodaterol Plus Ketoconazole n=32 participants at risk 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.
Gastrointestinal disorders Diarrhoea	0.00% 0/32 • First administration of trial medication until 6 days after last administration of trial medication	6.2% 2/32 • First administration of trial medication until 6 days after last administration of trial medication
Gastrointestinal disorders Dry mouth	3.1% 1/32 • First administration of trial medication until 6 days after last administration of trial medication	6.2% 2/32 • First administration of trial medication until 6 days after last administration of trial medication
Gastrointestinal disorders Nausea	0.00% 0/32 • First administration of trial medication until 6 days after last administration of trial medication	15.6% 5/32 • First administration of trial medication until 6 days after last administration of trial medication
Immune system disorders Allergy to arthropod bite	6.2% 2/32 • First administration of trial medication until 6 days after last administration of trial medication	0.00% 0/32 • First administration of trial medication until 6 days after last administration of trial medication
Nervous system disorders Headache	6.2% 2/32 • First administration of trial medication until 6 days after last administration of trial medication	3.1% 1/32 • First administration of trial medication until 6 days after last administration of trial medication
Nervous system disorders Tremor	0.00% 0/32 • First administration of trial medication until 6 days after last administration of trial medication	6.2% 2/32 • First administration of trial medication until 6 days after last administration of trial medication

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
Publication restrictions are in place

Restriction type: OTHER