Trial Outcomes & Findings for Efficacy (Bronchoprotection) and Safety of Orally Inhaled BI 1744 CL in Patients With Intermittent Asthma (NCT NCT00928668)

Results Overview

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 24 hours

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

24 hours post dose

Results posted on

2014-07-01

Participant Flow

This was a randomised, double-blind, placebo-controlled, 5-way crossover trial. The duration of each treatment period was 1 day with a 14 day washout period between treatments.

One patient was randomized, but the trial was put on hold so that the patient had to be discontinued and re-randomized. This causes a discrepancy between the 32 patients enrolled and the 31 patients reported for the participant flow.

Participant milestones

Participant milestones
Measure	Olo 5mcg / Olo 2mcg / Olo 10mcg / Placebo / Olo 20mcg Patients were administered Olodaterol 5 mcg qd in the first period, Olodaterol 2 mcg qd in the second period, Olodaterol 10 mcg qd in the third period, matching Placebo in the fourth period and Olodaterol 20 mcg qd in the fifth period. Olodaterol was administered via the Respimat inhaler.	Olo 10mcg / Olo 20mcg / Olo 2mcg / Olo 5mcg / Placebo Patients were administered Olodaterol 10 mcg qd in the first period, Olodaterol 20 mcg qd in the second period, Olodaterol 2 mcg qd in the third period, Olodaterol 5 mcg qd in the fourth period and matching Placebo in the fifth period. Olodaterol was administered via the Respimat inhaler.	Olo 2mcg / Placebo / Olo 20mcg / Olo 10mcg / Olo 5mcg Patients were administered Olodaterol 2 mcg qd in the first period, matching Placebo in the second period, Olodaterol 20 mcg qd in the third period, Olodaterol 10 mcg qd in the fourth period and Olodaterol 5 mcg qd in the fifth period. Olodaterol was administered via the Respimat inhaler.	Olo 20mcg / Olo 5mcg / Placebo / Olo 2mcg / Olo 10mcg Patients were administered Olodaterol 20 mcg qd in the first period, Olodaterol 5 mcg qd in the second period, matching Placebo in the third period, Olodaterol 2 mcg qd in the fourth period and Olodaterol 10 mcg qd in the fifth period. Olodaterol was administered via the Respimat inhaler.	Placebo / Olo 10mcg / Olo 5mcg / Olo 20mcg / Olo 2mcg Patients were administered matching Placebo in the first period, Olodaterol 10 mcg qd in the second period, Olodaterol 5 mcg qd in the third period, Olodaterol 20 mcg qd in the fourth period and Olodaterol 2 mcg qd in the fifth period. Olodaterol was administered via the Respimat inhaler.
Overall Study STARTED	7	7	7	4	6
Overall Study COMPLETED	6	6	6	3	5
Overall Study NOT COMPLETED	1	1	1	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Olo 5mcg / Olo 2mcg / Olo 10mcg / Placebo / Olo 20mcg Patients were administered Olodaterol 5 mcg qd in the first period, Olodaterol 2 mcg qd in the second period, Olodaterol 10 mcg qd in the third period, matching Placebo in the fourth period and Olodaterol 20 mcg qd in the fifth period. Olodaterol was administered via the Respimat inhaler.	Olo 10mcg / Olo 20mcg / Olo 2mcg / Olo 5mcg / Placebo Patients were administered Olodaterol 10 mcg qd in the first period, Olodaterol 20 mcg qd in the second period, Olodaterol 2 mcg qd in the third period, Olodaterol 5 mcg qd in the fourth period and matching Placebo in the fifth period. Olodaterol was administered via the Respimat inhaler.	Olo 2mcg / Placebo / Olo 20mcg / Olo 10mcg / Olo 5mcg Patients were administered Olodaterol 2 mcg qd in the first period, matching Placebo in the second period, Olodaterol 20 mcg qd in the third period, Olodaterol 10 mcg qd in the fourth period and Olodaterol 5 mcg qd in the fifth period. Olodaterol was administered via the Respimat inhaler.	Olo 20mcg / Olo 5mcg / Placebo / Olo 2mcg / Olo 10mcg Patients were administered Olodaterol 20 mcg qd in the first period, Olodaterol 5 mcg qd in the second period, matching Placebo in the third period, Olodaterol 2 mcg qd in the fourth period and Olodaterol 10 mcg qd in the fifth period. Olodaterol was administered via the Respimat inhaler.	Placebo / Olo 10mcg / Olo 5mcg / Olo 20mcg / Olo 2mcg Patients were administered matching Placebo in the first period, Olodaterol 10 mcg qd in the second period, Olodaterol 5 mcg qd in the third period, Olodaterol 20 mcg qd in the fourth period and Olodaterol 2 mcg qd in the fifth period. Olodaterol was administered via the Respimat inhaler.
Overall Study Adverse Event	1	0	0	0	0
Overall Study Protocol Violation	0	0	0	0	1
Overall Study Withdrawal by Subject	0	1	1	0	0
Overall Study Other reasons not listed above	0	0	0	1	0

Baseline Characteristics

Efficacy (Bronchoprotection) and Safety of Orally Inhaled BI 1744 CL in Patients With Intermittent Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Total n=31 Participants Total number of patients treated in the study. This was a randomised, double-blind, placebo-controlled, 5-way crossover trial. 31 patients were assigned randomly to one of 5 treatment sequences in which they received each of 5 treatments. The duration of each treatment period was 1 day with a 14 day washout period between treatments.
Age, Continuous	28.9 years STANDARD_DEVIATION 9.2 • n=99 Participants
Sex: Female, Male Female	17 Participants n=99 Participants
Sex: Female, Male Male	14 Participants n=99 Participants

PRIMARY outcome

Timeframe: 24 hours post dose

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and post-dose data for at least two periods for the same endpoint.

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 24 hours

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Matching Placebo delivered by the Respimat Inhaler.	Olodaterol (Olo) 2 mcg qd n=28 Participants Olodaterol 2 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 5 mcg qd n=27 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 10 mcg qd n=30 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 20 mcg qd n=29 Participants Olodaterol 20 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 24 Hours	0.793 Log base 2 (mg/ml) Standard Error 0.182	1.950 Log base 2 (mg/ml) Standard Error 0.186	2.504 Log base 2 (mg/ml) Standard Error 0.190	3.236 Log base 2 (mg/ml) Standard Error 0.179	3.777 Log base 2 (mg/ml) Standard Error 0.183

SECONDARY outcome

Timeframe: 30 minutes post dose

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and post-dose data for at least two periods for the same endpoint.

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 30 minutes

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Matching Placebo delivered by the Respimat Inhaler.	Olodaterol (Olo) 2 mcg qd n=28 Participants Olodaterol 2 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 5 mcg qd n=27 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 10 mcg qd n=30 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 20 mcg qd n=29 Participants Olodaterol 20 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 30 Minutes	0.393 Log base 2 (mg/ml) Standard Error 0.180	2.532 Log base 2 (mg/ml) Standard Error 0.184	3.029 Log base 2 (mg/ml) Standard Error 0.187	3.953 Log base 2 (mg/ml) Standard Error 0.177	4.617 Log base 2 (mg/ml) Standard Error 0.181

SECONDARY outcome

Timeframe: 4 hours post dose

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and post-dose data for at least two periods for the same endpoint.

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 4 hours

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Matching Placebo delivered by the Respimat Inhaler.	Olodaterol (Olo) 2 mcg qd n=28 Participants Olodaterol 2 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 5 mcg qd n=27 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 10 mcg qd n=30 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 20 mcg qd n=29 Participants Olodaterol 20 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 4 Hours	0.577 Log base 2 (mg/ml) Standard Error 0.214	2.602 Log base 2 (mg/ml) Standard Error 0.219	2.957 Log base 2 (mg/ml) Standard Error 0.223	4.126 Log base 2 (mg/ml) Standard Error 0.211	4.786 Log base 2 (mg/ml) Standard Error 0.215

SECONDARY outcome

Timeframe: 8 hours post dose

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and post-dose data for at least two periods for the same endpoint.

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 8 hours

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Matching Placebo delivered by the Respimat Inhaler.	Olodaterol (Olo) 2 mcg qd n=28 Participants Olodaterol 2 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 5 mcg qd n=27 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 10 mcg qd n=30 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 20 mcg qd n=29 Participants Olodaterol 20 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 8 Hours	0.576 Log base 2 (mg/ml) Standard Error 0.213	2.484 Log base 2 (mg/ml) Standard Error 0.218	3.050 Log base 2 (mg/ml) Standard Error 0.222	3.903 Log base 2 (mg/ml) Standard Error 0.210	4.796 Log base 2 (mg/ml) Standard Error 0.214

SECONDARY outcome

Timeframe: 32 hours post dose

Population: Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and post-dose data for at least two periods for the same endpoint.

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 32 hours

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Matching Placebo delivered by the Respimat Inhaler.	Olodaterol (Olo) 2 mcg qd n=28 Participants Olodaterol 2 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 5 mcg qd n=27 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 10 mcg qd n=30 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 20 mcg qd n=29 Participants Olodaterol 20 mcg qd delivered by the Respimat Inhaler.
Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 32 Hours	0.960 Log base 2 (mg/ml) Standard Error 0.200	2.189 Log base 2 (mg/ml) Standard Error 0.200	2.785 Log base 2 (mg/ml) Standard Error 0.203	3.074 Log base 2 (mg/ml) Standard Error 0.192	3.605 Log base 2 (mg/ml) Standard Error 0.197

SECONDARY outcome

Timeframe: 5 days

Population: The safety set included all patients who received any study medication.

Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsenings of baseline conditions were reported as Adverse Events (cardiac disorders and investigations).

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Matching Placebo delivered by the Respimat Inhaler.	Olodaterol (Olo) 2 mcg qd n=28 Participants Olodaterol 2 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 5 mcg qd n=28 Participants Olodaterol 5 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 10 mcg qd n=30 Participants Olodaterol 10 mcg qd delivered by the Respimat Inhaler.	Olodaterol (Olo) 20 mcg qd n=29 Participants Olodaterol 20 mcg qd delivered by the Respimat Inhaler.
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Cardiac disorders	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG Investigations	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Visit 6

Population: All patients in the Safety set who have a baseline value and post dose values for each planned time.

Laboratory testing: Average change from baseline of potassium and calcium measured on test-days