Determining Optimal Free Dose Combination of Tiotropium Bromide and BI 1744 CL in Chronic Obstructive Pulmonary Disease (COPD)

A Randomised, Double-blind, 8 Treatments, 4 Periods, Incomplete Crossover Study to Determine the Optimal Free Dose Combination of BI 1744 CL and Tiotropium Bromide (Both Delivered by the Respimat® Inhaler) After 4 Weeks Once Daily Treatment in Patients With COPD

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01040403

Enrollment

233

Registered

2009-12-29

Start date

2010-01-31

Completion date

Unknown

Last updated

2015-07-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Brief summary

The primary objective of this study is to determine the optimum once daily dose of BI 1744 CL and tiotropium in free dose combination (delivered by the Respimat inhaler) after four week treatment in patients with COPD.

Interventions

DRUGolodaterol (BI 1744) low

olodaterol (BI 1744) low

DRUGlow tiotropium bromide

low tiotropium bromide

DRUGolodaterol (BI 1744) high

olodaterol (BI 1744) high

DRUGmedium tiotropium bromide

medium tiotropium bromide

DRUGhigh tiotropium bromide

high tiotropium bromide

DRUGPlacebo

Placebo

DEVICERespimat

Respimat inhaler

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE

Eligibility

Sex/Gender

ALL

Age

40 Years to No maximum

Healthy volunteers

Inclusion criteria

1. All patients must sign an informed consent 2. All patients must have a diagnosis of chronic obstructive pulmonary disease (COPD) must meet the following spirometric criteria: a post-bronchodilator forced expiratory flow in 1 second (FEV1) =\<30% of predicted normal and \<80% of predicted normal and a post bronchodilator FEV1 / forced vital capacity (FVC) \<70% at Visit 1 4. Male or female patients, 40 years of age or older. 5. Patients must be current or ex-smokers with a smoking history of more than 10 pack years

Exclusion criteria

* Patients with a significant disease other than COPD; * Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; * Patients with a history of asthma or a total blood eosinophil count \>=600/mm3. * Patients with any of the following conditions: a diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists) a diagnosis of paroxysmal tachycardia - Patients with any of the following conditions: a history of myocardial infarction within 1 year of screening visit a diagnosis of clinically relevant cardiac arrhythmia a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years * Patients who have undergone thoracotomy with pulmonary resection * Patients being treated with the following concomitant medications: medications that prolong the QT/QTc interval oral Beta-adrenergics oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day \- Pregnant or nursing women

Design outcomes

Primary

Measure	Time frame	Description
Trough FEV1 Response	Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29	Adjusted means of the trough forced expiratory volume in one second (FEV1) response (L) after four weeks treatment. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Secondary

Measure	Time frame	Description
FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29	Adjusted means of forced expiratory volume in one second (FEV1) area under the curve (AUC) 0-3 hour and AUC 0-6 hour responses \[L\] after 4 weeks treatment calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FEV1 AUC 0-3h Response After the First Dose	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1	Adjusted means of Forced Expiratory Volume in One Second (FEV1) Area Under Curve (AUC) 0-3h response \[L\] after the first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FEV1 Peak 0-3h Response	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29	Adjusted means of the FEV1 peak value over the time from 0 to 3 hours (peak 0-3h) response \[L\] after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FEV1 Peak 0-3h Response After the First Dose	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1	Adjusted means of the FEV1 peak 0-3h response \[L\] after the first dose of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FVC AUC 0-3h and FEV1 AUC 0-6h Responses	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29	Adjusted means of the FVC AUC 0-3h and AUC 0-6h responses \[L\] after 4 weeks of treatment, calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FVC AUC 0-3h Response After First Dose	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on days 1	Adjusted means of the FVC AUC 0-3h response \[L\] after first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FVC Peak 0-3h Response	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29	Adjusted means of the FVC peak 0-3h response \[L\] after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
FVC Peak 0-3h Response After the First Dose	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1	Adjusted mean of the FVC peak 0-3h response \[L\] after the first dose. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
PEF AUC 0-3h and AUC 0-6h Responses	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29	Adjusted means of the Peak Expiratory Flow (PEF) AUC 0-3h and AUC 0-6h responses in Litres / minute (L/min) after 4 weeks of treatment, calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
PEF AUC 0-3h Response After the First Dose	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1	Adjusted means of the Area under the curve from 0 to 3 h response in Litres / minutes of the peak expiratory flow after the first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
Trough Forced Vital Capacity (FVC) Response	Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29	Adjusted means of trough FVC (forced vital capacity) response \[L\] after 4 weeks treatment. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
PEF Peak 0-3h Response After the First Dose	Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1	Adjusted means of the Peak Expiratory flow from 0 to 3 hours response in L/min after the first dose of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
Individual FEV1 Measurements at Each Time Point on Day 29	Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29	Adjusted means of the FEV1 measurements \[L\] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
Individual FVC Measurements at Each Time Point on Day 29	Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29	Adjusted means of the FVC measurements \[L\] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
Individual PEF Measurements at Each Time Point on Day 29	Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29	Adjusted means of the PEF measurements \[L/min\] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.
Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Weeks 1 and 4	Adjusted means of the weekly mean number of puffs of rescue medication during the whole day : the rescue medication was a salbutamol \[albuterol\] dose (100 mcg per puff).
Physicians Global Evaluation	Days 1 and 29	Adjusted means of the Physicians Global Evaluation of the patient's respiratory condition on days 1 and 29. The score was evaluated on a 8-points scale : * Poor : 1,2 * Fair : 3,4 * Good : 5,6 * Excellent : 7,8
Patients Global Rating	Day 29	Adjusted means of the Global Rating of the patients' health (respiratory condition) on day 29. The score was evaluated on a 7-point scale : * 1 : very much better * 2 : much better * 3 : a little better * 4 : no change * 5 : a little worse * 6 : much worse * 7 : very much worse
Pulse Rate Recorded in Conjunction With Spirometry	Baseline and 30 min post-dose on day 29	Pulse rate recorded in conjunction with spirometry change from baseline at 30 minutes post-dose on day 29 in beats per minute (bpm).
Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Baseline and 30 min post-dose on day 29	Systolic and diastolic blood pressure recorded in conjunction with spirometry change from baseline on day 29 in millimetres of mercury (mmHg).
PEF Peak 0-3h Response	Baseline 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29	Adjusted means of the peak expiratory flow from 0 to 3 hours (PEF peak 0-3h) response in L/min after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Countries

Canada, Germany, Netherlands, Sweden

Participant flow

Pre-assignment details

This was a randomised, 4-period incomplete cross-over trial. 233 patients were randomized to one of 14 treatment sequences and 232 of them were treated. It was a double-blind trial in which each treatment period lasted 4 weeks with a washout period of 21 days between each.

Participants by arm

Arm	Count
Overall Study A randomised, double-blind, 8 treatment, 4 period, incomplete crossover study. Each treatment period was separated by a washout period of 3 weeks. The 8 treatments, administered by oral inhalation from separate Respimat inhalers, once daily, in the morning, were: * Olodaterol 5 µg and placebo * Tiotropium 1.25 µg and Olodaterol 5 µg free combination inhalation solution * Tiotropium 2.5 µg and Olodaterol 5 µg free combination inhalation solution * Tiotropium 5 µg and Olodaterol 5 µg free combination inhalation solution * Olodaterol 10 µg and placebo * Tiotropium 1.25 µg and Olodaterol 10 µg free combination inhalation solution * Tiotropium 2.5 µg and Olodaterol 10 µg free combination inhalation solution * Tiotropium 5 µg and Olodaterol 10 µg free combination inhalation solution	232
Total	232

Arm

Count

Overall Study

A randomised, double-blind, 8 treatment, 4 period, incomplete crossover study. Each treatment period was separated by a washout period of 3 weeks. The 8 treatments, administered by oral inhalation from separate Respimat inhalers, once daily, in the morning, were: * Olodaterol 5 µg and placebo * Tiotropium 1.25 µg and Olodaterol 5 µg free combination inhalation solution * Tiotropium 2.5 µg and Olodaterol 5 µg free combination inhalation solution * Tiotropium 5 µg and Olodaterol 5 µg free combination inhalation solution * Olodaterol 10 µg and placebo * Tiotropium 1.25 µg and Olodaterol 10 µg free combination inhalation solution * Tiotropium 2.5 µg and Olodaterol 10 µg free combination inhalation solution * Tiotropium 5 µg and Olodaterol 10 µg free combination inhalation solution

232

Total

232

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	10
Overall Study	Lost to Follow-up	1
Overall Study	Not treated	1
Overall Study	Other reason not defined above	6
Overall Study	Protocol Violation	2

Baseline characteristics

Characteristic	Overall Study
Age, Continuous	63.3 years STANDARD_DEVIATION 8.2
Sex: Female, Male Female	99 Participants
Sex: Female, Male Male	133 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	15 / 108	15 / 109	11 / 113	11 / 109	12 / 109	13 / 110	7 / 110	6 / 111
serious Total, serious adverse events	4 / 108	1 / 109	3 / 113	1 / 109	2 / 109	1 / 110	5 / 110	0 / 111

Outcome results

Primary

Trough FEV1 Response

Adjusted means of the trough forced expiratory volume in one second (FEV1) response (L) after four weeks treatment. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29

Population: Full Analysis Set (FAS) which comprised all patients in the treated set who provided baseline (study baseline) data and at least 1 on-treatment efficacy value for the primary endpoint after 4 weeks on treatment.

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	Trough FEV1 Response	0.071 Litres	Standard Deviation 0.018
T+O 1.25/5	Trough FEV1 Response	0.125 Litres	Standard Deviation 0.018
T+O 2.5/5	Trough FEV1 Response	0.136 Litres	Standard Deviation 0.018
T+O 5/5	Trough FEV1 Response	0.155 Litres	Standard Deviation 0.018
Olo 10	Trough FEV1 Response	0.083 Litres	Standard Deviation 0.018
T+O 1.25/10	Trough FEV1 Response	0.134 Litres	Standard Deviation 0.018
T+O 2.5/10	Trough FEV1 Response	0.166 Litres	Standard Deviation 0.018
T+O 5/10	Trough FEV1 Response	0.163 Litres	Standard Deviation 0.018

95% CI: [0.016, 0.092]Mixed Models Analysis

95% CI: [0.027, 0.103]Mixed Models Analysis

95% CI: [0.046, 0.122]Mixed Models Analysis

95% CI: [-0.027, 0.049]Mixed Models Analysis

95% CI: [-0.008, 0.069]Mixed Models Analysis

95% CI: [-0.019, 0.058]Mixed Models Analysis

95% CI: [0.013, 0.089]Mixed Models Analysis

95% CI: [0.045, 0.122]Mixed Models Analysis

95% CI: [0.042, 0.119]Mixed Models Analysis

95% CI: [-0.006, 0.071]Mixed Models Analysis

95% CI: [-0.009, 0.068]Mixed Models Analysis

95% CI: [-0.041, 0.035]Mixed Models Analysis

Secondary

FEV1 AUC 0-3h and FEV1 AUC 0-6h Response

Adjusted means of forced expiratory volume in one second (FEV1) area under the curve (AUC) 0-3 hour and AUC 0-6 hour responses \[L\] after 4 weeks treatment calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Olo 5	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-3h	0.183 Litres	Standard Deviation 0.02
Olo 5	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-6h	0.188 Litres	Standard Deviation 0.02
T+O 1.25/5	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-3h	0.258 Litres	Standard Deviation 0.02
T+O 1.25/5	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-6h	0.267 Litres	Standard Deviation 0.02
T+O 2.5/5	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-3h	0.280 Litres	Standard Deviation 0.02
T+O 2.5/5	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-6h	0.287 Litres	Standard Deviation 0.02
T+O 5/5	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-3h	0.302 Litres	Standard Deviation 0.02
T+O 5/5	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-6h	0.307 Litres	Standard Deviation 0.02
Olo 10	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-3h	0.191 Litres	Standard Deviation 0.02
Olo 10	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-6h	0.198 Litres	Standard Deviation 0.02
T+O 1.25/10	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-3h	0.288 Litres	Standard Deviation 0.02
T+O 1.25/10	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-6h	0.296 Litres	Standard Deviation 0.02
T+O 2.5/10	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-6h	0.320 Litres	Standard Deviation 0.02
T+O 2.5/10	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-3h	0.319 Litres	Standard Deviation 0.02
T+O 5/10	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-3h	0.334 Litres	Standard Deviation 0.02
T+O 5/10	FEV1 AUC 0-3h and FEV1 AUC 0-6h Response	AUC 0-6h	0.342 Litres	Standard Deviation 0.02

Comparison: AUC 0-3h95% CI: [0.035, 0.114]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.057, 0.137]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.079, 0.159]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-0.017, 0.062]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.004, 0.085]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-0.018, 0.062]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.057, 0.137]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.088, 0.168]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.103, 0.183]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-0.009, 0.071]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.006, 0.086]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-0.025, 0.055]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.04, 0.117]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.06, 0.137]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.08, 0.157]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.018, 0.058]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.001, 0.079]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.019, 0.058]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.06, 0.136]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.083, 0.159]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.105, 0.182]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.016, 0.062]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.007, 0.084]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.016, 0.061]Mixed Models Analysis

Secondary

FEV1 AUC 0-3h Response After the First Dose

Adjusted means of Forced Expiratory Volume in One Second (FEV1) Area Under Curve (AUC) 0-3h response \[L\] after the first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	FEV1 AUC 0-3h Response After the First Dose	0.204 Litres	Standard Deviation 0.017
T+O 1.25/5	FEV1 AUC 0-3h Response After the First Dose	0.181 Litres	Standard Deviation 0.017
T+O 2.5/5	FEV1 AUC 0-3h Response After the First Dose	0.209 Litres	Standard Deviation 0.017
T+O 5/5	FEV1 AUC 0-3h Response After the First Dose	0.205 Litres	Standard Deviation 0.017
Olo 10	FEV1 AUC 0-3h Response After the First Dose	0.188 Litres	Standard Deviation 0.017
T+O 1.25/10	FEV1 AUC 0-3h Response After the First Dose	0.227 Litres	Standard Deviation 0.017
T+O 2.5/10	FEV1 AUC 0-3h Response After the First Dose	0.219 Litres	Standard Deviation 0.017
T+O 5/10	FEV1 AUC 0-3h Response After the First Dose	0.230 Litres	Standard Deviation 0.017

95% CI: [-0.011, 0.059]Mixed Models Analysis

95% CI: [-0.039, 0.031]Mixed Models Analysis

95% CI: [0.004, 0.073]Mixed Models Analysis

95% CI: [-0.004, 0.066]Mixed Models Analysis

95% CI: [-0.058, 0.012]Mixed Models Analysis

95% CI: [-0.029, 0.04]Mixed Models Analysis

95% CI: [-0.034, 0.036]Mixed Models Analysis

95% CI: [-0.006, 0.063]Mixed Models Analysis

95% CI: [0.006, 0.076]Mixed Models Analysis

95% CI: [-0.043, 0.027]Mixed Models Analysis

95% CI: [-0.032, 0.037]Mixed Models Analysis

95% CI: [-0.025, 0.045]Mixed Models Analysis

Secondary

FEV1 Peak 0-3h Response

Adjusted means of the FEV1 peak value over the time from 0 to 3 hours (peak 0-3h) response \[L\] after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	FEV1 Peak 0-3h Response	0.264 Litres	Standard Error 0.023
T+O 1.25/5	FEV1 Peak 0-3h Response	0.353 Litres	Standard Error 0.023
T+O 2.5/5	FEV1 Peak 0-3h Response	0.355 Litres	Standard Error 0.023
T+O 5/5	FEV1 Peak 0-3h Response	0.379 Litres	Standard Error 0.023
Olo 10	FEV1 Peak 0-3h Response	0.267 Litres	Standard Error 0.023
T+O 1.25/10	FEV1 Peak 0-3h Response	0.374 Litres	Standard Error 0.023
T+O 2.5/10	FEV1 Peak 0-3h Response	0.399 Litres	Standard Error 0.023
T+O 5/10	FEV1 Peak 0-3h Response	0.412 Litres	Standard Error 0.023

95% CI: [0.041, 0.138]Mixed Models Analysis

95% CI: [0.043, 0.139]Mixed Models Analysis

95% CI: [0.066, 0.164]Mixed Models Analysis

95% CI: [-0.046, 0.05]Mixed Models Analysis

95% CI: [-0.023, 0.074]Mixed Models Analysis

95% CI: [-0.025, 0.072]Mixed Models Analysis

95% CI: [0.059, 0.156]Mixed Models Analysis

95% CI: [0.084, 0.181]Mixed Models Analysis

95% CI: [0.096, 0.193]Mixed Models Analysis

95% CI: [-0.024, 0.074]Mixed Models Analysis

95% CI: [-0.01, 0.086]Mixed Models Analysis

95% CI: [-0.036, 0.061]Mixed Models Analysis

Secondary

FEV1 Peak 0-3h Response After the First Dose

Adjusted means of the FEV1 peak 0-3h response \[L\] after the first dose of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	FEV1 Peak 0-3h Response After the First Dose	0.287 Litres	Standard Error 0.019
T+O 1.25/5	FEV1 Peak 0-3h Response After the First Dose	0.267 Litres	Standard Error 0.019
T+O 2.5/5	FEV1 Peak 0-3h Response After the First Dose	0.300 Litres	Standard Error 0.019
T+O 5/5	FEV1 Peak 0-3h Response After the First Dose	0.298 Litres	Standard Error 0.019
Olo 10	FEV1 Peak 0-3h Response After the First Dose	0.270 Litres	Standard Error 0.019
T+O 1.25/10	FEV1 Peak 0-3h Response After the First Dose	0.324 Litres	Standard Error 0.019
T+O 2.5/10	FEV1 Peak 0-3h Response After the First Dose	0.315 Litres	Standard Error 0.019
T+O 5/10	FEV1 Peak 0-3h Response After the First Dose	0.317 Litres	Standard Error 0.019

95% CI: [-0.059, 0.02]Mixed Models Analysis

95% CI: [-0.026, 0.053]Mixed Models Analysis

95% CI: [-0.028, 0.051]Mixed Models Analysis

95% CI: [-0.006, 0.072]Mixed Models Analysis

95% CI: [-0.009, 0.071]Mixed Models Analysis

95% CI: [-0.041, 0.037]Mixed Models Analysis

95% CI: [0.015, 0.093]Mixed Models Analysis

95% CI: [0.006, 0.084]Mixed Models Analysis

95% CI: [0.008, 0.087]Mixed Models Analysis

95% CI: [-0.049, 0.031]Mixed Models Analysis

95% CI: [-0.046, 0.033]Mixed Models Analysis

95% CI: [-0.037, 0.042]Mixed Models Analysis

Secondary

FVC AUC 0-3h and FEV1 AUC 0-6h Responses

Adjusted means of the FVC AUC 0-3h and AUC 0-6h responses \[L\] after 4 weeks of treatment, calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Olo 5	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-3h	0.278 Litres	Standard Error 0.032
Olo 5	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-6h	0.282 Litres	Standard Error 0.032
T+O 1.25/5	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-3h	0.422 Litres	Standard Error 0.032
T+O 1.25/5	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-6h	0.421 Litres	Standard Error 0.032
T+O 2.5/5	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-3h	0.429 Litres	Standard Error 0.032
T+O 2.5/5	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-6h	0.432 Litres	Standard Error 0.032
T+O 5/5	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-3h	0.410 Litres	Standard Error 0.032
T+O 5/5	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-6h	0.414 Litres	Standard Error 0.032
Olo 10	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-3h	0.279 Litres	Standard Error 0.032
Olo 10	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-6h	0.277 Litres	Standard Error 0.032
T+O 1.25/10	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-3h	0.455 Litres	Standard Error 0.032
T+O 1.25/10	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-6h	0.466 Litres	Standard Error 0.032
T+O 2.5/10	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-6h	0.456 Litres	Standard Error 0.032
T+O 2.5/10	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-3h	0.454 Litres	Standard Error 0.032
T+O 5/10	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-3h	0.479 Litres	Standard Error 0.032
T+O 5/10	FVC AUC 0-3h and FEV1 AUC 0-6h Responses	AUC 0-6h	0.490 Litres	Standard Error 0.032

Comparison: AUC 0-3h95% CI: [0.084, 0.202]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.092, 0.21]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.072, 0.191]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-0.051, 0.066]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-0.071, 0.048]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-0.079, 0.039]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.116, 0.234]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [0.14, 0.259]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-0.06, 0.059]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-0.035, 0.083]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.081, 0.197]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.092, 0.207]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.073, 0.189]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.047, 0.068]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.066, 0.051]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.076, 0.039]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.131, 0.247]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.121, 0.236]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [0.155, 0.271]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.069, 0.048]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.033, 0.082]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.023, 0.092]Mixed Models Analysis

Secondary

FVC AUC 0-3h Response After First Dose

Adjusted means of the FVC AUC 0-3h response \[L\] after first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on days 1

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	FVC AUC 0-3h Response After First Dose	0.333 Litres	Standard Error 0.029
T+O 1.25/5	FVC AUC 0-3h Response After First Dose	0.285 Litres	Standard Error 0.029
T+O 2.5/5	FVC AUC 0-3h Response After First Dose	0.326 Litres	Standard Error 0.029
T+O 5/5	FVC AUC 0-3h Response After First Dose	0.319 Litres	Standard Error 0.03
Olo 10	FVC AUC 0-3h Response After First Dose	0.303 Litres	Standard Error 0.029
T+O 1.25/10	FVC AUC 0-3h Response After First Dose	0.393 Litres	Standard Error 0.03
T+O 2.5/10	FVC AUC 0-3h Response After First Dose	0.363 Litres	Standard Error 0.029
T+O 5/10	FVC AUC 0-3h Response After First Dose	0.359 Litres	Standard Error 0.029

95% CI: [-0.106, 0.01]Mixed Models Analysis

95% CI: [-0.065, 0.051]Mixed Models Analysis

95% CI: [-0.072, 0.044]Mixed Models Analysis

95% CI: [-0.017, 0.099]Mixed Models Analysis

95% CI: [-0.024, 0.093]Mixed Models Analysis

95% CI: [-0.065, 0.051]Mixed Models Analysis

95% CI: [0.032, 0.148]Mixed Models Analysis

95% CI: [0.001, 0.118]Mixed Models Analysis

95% CI: [-0.002, 0.114]Mixed Models Analysis

95% CI: [-0.089, 0.028]Mixed Models Analysis

95% CI: [-0.092, 0.024]Mixed Models Analysis

95% CI: [-0.062, 0.055]Mixed Models Analysis

Secondary

FVC Peak 0-3h Response

Adjusted means of the FVC peak 0-3h response \[L\] after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	FVC Peak 0-3h Response	0.415 Litres	Standard Error 0.035
T+O 1.25/5	FVC Peak 0-3h Response	0.570 Litres	Standard Error 0.035
T+O 2.5/5	FVC Peak 0-3h Response	0.563 Litres	Standard Error 0.035
T+O 5/5	FVC Peak 0-3h Response	0.542 Litres	Standard Error 0.035
Olo 10	FVC Peak 0-3h Response	0.411 Litres	Standard Error 0.035
T+O 1.25/10	FVC Peak 0-3h Response	0.585 Litres	Standard Error 0.035
T+O 2.5/10	FVC Peak 0-3h Response	0.593 Litres	Standard Error 0.035
T+O 5/10	FVC Peak 0-3h Response	0.615 Litres	Standard Error 0.035

95% CI: [0.087, 0.223]Mixed Models Analysis

95% CI: [0.079, 0.215]Mixed Models Analysis

95% CI: [0.058, 0.195]Mixed Models Analysis

95% CI: [-0.075, 0.06]Mixed Models Analysis

95% CI: [-0.097, 0.041]Mixed Models Analysis

95% CI: [-0.089, 0.048]Mixed Models Analysis

95% CI: [0.106, 0.242]Mixed Models Analysis

95% CI: [0.113, 0.25]Mixed Models Analysis

95% CI: [0.135, 0.272]Mixed Models Analysis

95% CI: [-0.061, 0.076]Mixed Models Analysis

95% CI: [-0.038, 0.098]Mixed Models Analysis

95% CI: [-0.046, 0.09]Mixed Models Analysis

Secondary

FVC Peak 0-3h Response After the First Dose

Adjusted mean of the FVC peak 0-3h response \[L\] after the first dose. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	FVC Peak 0-3h Response After the First Dose	0.473 Litres	Standard Error 0.031
T+O 1.25/5	FVC Peak 0-3h Response After the First Dose	0.423 Litres	Standard Error 0.031
T+O 2.5/5	FVC Peak 0-3h Response After the First Dose	0.481 Litres	Standard Error 0.031
T+O 5/5	FVC Peak 0-3h Response After the First Dose	0.462 Litres	Standard Error 0.032
Olo 10	FVC Peak 0-3h Response After the First Dose	0.436 Litres	Standard Error 0.031
T+O 1.25/10	FVC Peak 0-3h Response After the First Dose	0.547 Litres	Standard Error 0.032
T+O 2.5/10	FVC Peak 0-3h Response After the First Dose	0.517 Litres	Standard Error 0.031
T+O 5/10	FVC Peak 0-3h Response After the First Dose	0.505 Litres	Standard Error 0.031

95% CI: [-0.114, 0.013]Mixed Models Analysis

95% CI: [-0.055, 0.071]Mixed Models Analysis

95% CI: [-0.074, 0.053]Mixed Models Analysis

95% CI: [-0.004, 0.122]Mixed Models Analysis

95% CI: [-0.024, 0.104]Mixed Models Analysis

95% CI: [-0.082, 0.045]Mixed Models Analysis

95% CI: [0.047, 0.174]Mixed Models Analysis

95% CI: [0.017, 0.144]Mixed Models Analysis

95% CI: [0.005, 0.132]Mixed Models Analysis

95% CI: [-0.094, 0.034]Mixed Models Analysis

95% CI: [-0.105, 0.021]Mixed Models Analysis

95% CI: [-0.075, 0.052]Mixed Models Analysis

Secondary

Individual FEV1 Measurements at Each Time Point on Day 29

Adjusted means of the FEV1 measurements \[L\] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	1.521 Litres	Standard Error 0.021
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	1.549 Litres	Standard Error 0.021
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	1.517 Litres	Standard Error 0.022
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	1.410 Litres	Standard Error 0.018
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	1.543 Litres	Standard Error 0.021
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	1.419 Litres	Standard Error 0.018
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	1.431 Litres	Standard Error 0.02
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	1.552 Litres	Standard Error 0.021
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	1.483 Litres	Standard Error 0.022
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	1.516 Litres	Standard Error 0.021
Olo 5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	1.553 Litres	Standard Error 0.022
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	1.625 Litres	Standard Error 0.021
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	1.555 Litres	Standard Error 0.022
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	1.648 Litres	Standard Error 0.022
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	1.621 Litres	Standard Error 0.021
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	1.464 Litres	Standard Error 0.018
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	1.605 Litres	Standard Error 0.022
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	1.487 Litres	Standard Error 0.02
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	1.595 Litres	Standard Error 0.021
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	1.473 Litres	Standard Error 0.018
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	1.570 Litres	Standard Error 0.021
T+O 1.25/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	1.622 Litres	Standard Error 0.021
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	1.488 Litres	Standard Error 0.02
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	1.656 Litres	Standard Error 0.021
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	1.631 Litres	Standard Error 0.021
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	1.481 Litres	Standard Error 0.018
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	1.484 Litres	Standard Error 0.018
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	1.626 Litres	Standard Error 0.021
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	1.553 Litres	Standard Error 0.022
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	1.654 Litres	Standard Error 0.021
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	1.597 Litres	Standard Error 0.021
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	1.659 Litres	Standard Error 0.022
T+O 2.5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	1.622 Litres	Standard Error 0.021
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	1.503 Litres	Standard Error 0.018
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	1.687 Litres	Standard Error 0.022
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	1.630 Litres	Standard Error 0.021
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	1.647 Litres	Standard Error 0.022
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	1.654 Litres	Standard Error 0.021
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	1.671 Litres	Standard Error 0.022
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	1.633 Litres	Standard Error 0.021
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	1.659 Litres	Standard Error 0.021
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	1.516 Litres	Standard Error 0.02
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	1.563 Litres	Standard Error 0.022
T+O 5/5	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	1.491 Litres	Standard Error 0.018
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	1.540 Litres	Standard Error 0.021
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	1.414 Litres	Standard Error 0.018
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	1.447 Litres	Standard Error 0.02
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	1.431 Litres	Standard Error 0.018
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	1.491 Litres	Standard Error 0.022
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	1.524 Litres	Standard Error 0.021
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	1.527 Litres	Standard Error 0.021
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	1.556 Litres	Standard Error 0.021
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	1.567 Litres	Standard Error 0.022
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	1.563 Litres	Standard Error 0.021
Olo 10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	1.547 Litres	Standard Error 0.022
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	1.467 Litres	Standard Error 0.018
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	1.576 Litres	Standard Error 0.022
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	1.605 Litres	Standard Error 0.021
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	1.663 Litres	Standard Error 0.021
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	1.627 Litres	Standard Error 0.021
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	1.661 Litres	Standard Error 0.021
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	1.636 Litres	Standard Error 0.022
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	1.498 Litres	Standard Error 0.02
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	1.482 Litres	Standard Error 0.018
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	1.671 Litres	Standard Error 0.022
T+O 1.25/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	1.640 Litres	Standard Error 0.021
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	1.526 Litres	Standard Error 0.02
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	1.655 Litres	Standard Error 0.021
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	1.690 Litres	Standard Error 0.022
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	1.504 Litres	Standard Error 0.018
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	1.658 Litres	Standard Error 0.021
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	1.699 Litres	Standard Error 0.021
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	1.593 Litres	Standard Error 0.022
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	1.656 Litres	Standard Error 0.022
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	1.676 Litres	Standard Error 0.021
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	1.643 Litres	Standard Error 0.021
T+O 2.5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	1.514 Litres	Standard Error 0.018
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	1.708 Litres	Standard Error 0.021
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	1.660 Litres	Standard Error 0.021
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	1.716 Litres	Standard Error 0.022
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	1.601 Litres	Standard Error 0.022
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	1.711 Litres	Standard Error 0.021
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	1.511 Litres	Standard Error 0.018
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	1.527 Litres	Standard Error 0.02
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	1.688 Litres	Standard Error 0.021
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	1.500 Litres	Standard Error 0.018
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	1.675 Litres	Standard Error 0.021
T+O 5/10	Individual FEV1 Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	1.687 Litres	Standard Error 0.022

Secondary

Individual FVC Measurements at Each Time Point on Day 29

Adjusted means of the FVC measurements \[L\] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	3.061 Litres	Standard Error 0.035
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	2.882 Litres	Standard Error 0.029
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	3.018 Litres	Standard Error 0.033
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	3.035 Litres	Standard Error 0.035
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	3.077 Litres	Standard Error 0.034
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	3.067 Litres	Standard Error 0.035
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	3.054 Litres	Standard Error 0.035
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	2.999 Litres	Standard Error 0.033
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	3.036 Litres	Standard Error 0.034
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	2.891 Litres	Standard Error 0.032
Olo 5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	2.877 Litres	Standard Error 0.029
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	3.007 Litres	Standard Error 0.032
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	3.216 Litres	Standard Error 0.034
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	3.163 Litres	Standard Error 0.035
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	2.961 Litres	Standard Error 0.029
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	2.981 Litres	Standard Error 0.029
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	3.193 Litres	Standard Error 0.035
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	3.130 Litres	Standard Error 0.033
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	3.181 Litres	Standard Error 0.035
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	3.171 Litres	Standard Error 0.033
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	3.222 Litres	Standard Error 0.035
T+O 1.25/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	3.174 Litres	Standard Error 0.034
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	3.233 Litres	Standard Error 0.035
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	3.009 Litres	Standard Error 0.031
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	3.197 Litres	Standard Error 0.035
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	3.190 Litres	Standard Error 0.034
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	3.120 Litres	Standard Error 0.033
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	3.204 Litres	Standard Error 0.034
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	3.234 Litres	Standard Error 0.034
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	3.145 Litres	Standard Error 0.033
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	3.188 Litres	Standard Error 0.035
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	3.002 Litres	Standard Error 0.029
T+O 2.5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	2.996 Litres	Standard Error 0.029
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	3.162 Litres	Standard Error 0.034
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	3.200 Litres	Standard Error 0.036
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	3.183 Litres	Standard Error 0.035
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	3.172 Litres	Standard Error 0.034
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	2.954 Litres	Standard Error 0.029
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	3.178 Litres	Standard Error 0.035
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	3.087 Litres	Standard Error 0.033
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	2.982 Litres	Standard Error 0.029
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	3.208 Litres	Standard Error 0.035
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	3.179 Litres	Standard Error 0.035
T+O 5/5	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	3.012 Litres	Standard Error 0.032
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	3.019 Litres	Standard Error 0.035
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	2.877 Litres	Standard Error 0.029
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	2.904 Litres	Standard Error 0.032
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	2.889 Litres	Standard Error 0.029
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	3.019 Litres	Standard Error 0.033
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	3.032 Litres	Standard Error 0.034
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	3.071 Litres	Standard Error 0.034
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	3.081 Litres	Standard Error 0.035
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	3.054 Litres	Standard Error 0.034
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	3.009 Litres	Standard Error 0.033
Olo 10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	3.028 Litres	Standard Error 0.035
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	3.222 Litres	Standard Error 0.035
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	3.036 Litres	Standard Error 0.032
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	3.190 Litres	Standard Error 0.034
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	3.006 Litres	Standard Error 0.029
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	3.258 Litres	Standard Error 0.035
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	3.141 Litres	Standard Error 0.033
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	3.204 Litres	Standard Error 0.034
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	3.228 Litres	Standard Error 0.035
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	3.266 Litres	Standard Error 0.035
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	3.264 Litres	Standard Error 0.036
T+O 1.25/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	3.020 Litres	Standard Error 0.029
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	3.032 Litres	Standard Error 0.032
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	3.214 Litres	Standard Error 0.035
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	3.192 Litres	Standard Error 0.033
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	3.020 Litres	Standard Error 0.029
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	3.208 Litres	Standard Error 0.035
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	3.012 Litres	Standard Error 0.029
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	3.147 Litres	Standard Error 0.033
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	3.215 Litres	Standard Error 0.034
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	3.267 Litres	Standard Error 0.035
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	3.227 Litres	Standard Error 0.035
T+O 2.5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	3.249 Litres	Standard Error 0.034
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	3.281 Litres	Standard Error 0.035
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	3.219 Litres	Standard Error 0.033
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	3.261 Litres	Standard Error 0.035
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	3.303 Litres	Standard Error 0.035
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	3.148 Litres	Standard Error 0.033
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	3.016 Litres	Standard Error 0.029
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	3.275 Litres	Standard Error 0.034
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	3.032 Litres	Standard Error 0.032
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	3.252 Litres	Standard Error 0.035
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	3.007 Litres	Standard Error 0.029
T+O 5/10	Individual FVC Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	3.239 Litres	Standard Error 0.034

Secondary

Individual PEF Measurements at Each Time Point on Day 29

Adjusted means of the PEF measurements \[L/min\] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	261.890 L/min	Standard Error 4.42
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	272.141 L/min	Standard Error 4.5
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	268.680 L/min	Standard Error 4.523
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	246.557 L/min	Standard Error 4.061
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	266.451 L/min	Standard Error 4.485
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	245.758 L/min	Standard Error 3.892
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	245.661 L/min	Standard Error 4.165
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	269.187 L/min	Standard Error 4.606
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	254.967 L/min	Standard Error 4.259
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	257.326 L/min	Standard Error 4.548
Olo 5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	269.067 L/min	Standard Error 4.649
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	287.181 L/min	Standard Error 4.621
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	267.969 L/min	Standard Error 4.272
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	292.962 L/min	Standard Error 4.665
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	286.382 L/min	Standard Error 4.499
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	260.901 L/min	Standard Error 4.064
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	284.028 L/min	Standard Error 4.537
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	264.412 L/min	Standard Error 4.18
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	279.892 L/min	Standard Error 4.434
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	262.239 L/min	Standard Error 3.895
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	275.045 L/min	Standard Error 4.563
T+O 1.25/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	287.917 L/min	Standard Error 4.514
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	265.177 L/min	Standard Error 4.139
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	295.820 L/min	Standard Error 4.578
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	295.843 L/min	Standard Error 4.497
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	263.662 L/min	Standard Error 4.037
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	264.202 L/min	Standard Error 3.87
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	293.878 L/min	Standard Error 4.474
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	273.340 L/min	Standard Error 4.235
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	297.483 L/min	Standard Error 4.46
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	279.309 L/min	Standard Error 4.519
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	296.736 L/min	Standard Error 4.62
T+O 2.5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	287.635 L/min	Standard Error 4.393
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	270.565 L/min	Standard Error 3.926
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	300.076 L/min	Standard Error 4.661
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	286.288 L/min	Standard Error 4.603
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	295.703 L/min	Standard Error 4.575
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	295.911 L/min	Standard Error 4.55
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	303.099 L/min	Standard Error 4.707
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	289.866 L/min	Standard Error 4.472
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	297.415 L/min	Standard Error 4.536
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	271.793 L/min	Standard Error 4.204
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	275.329 L/min	Standard Error 4.307
T+O 5/5	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	269.754 L/min	Standard Error 4.11
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	269.220 L/min	Standard Error 4.492
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	249.356 L/min	Standard Error 4.054
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	253.921 L/min	Standard Error 4.157
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	251.517 L/min	Standard Error 3.886
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	259.301 L/min	Standard Error 4.252
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	264.909 L/min	Standard Error 4.539
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	263.293 L/min	Standard Error 4.412
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	272.318 L/min	Standard Error 4.597
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	274.334 L/min	Standard Error 4.641
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	274.466 L/min	Standard Error 4.478
Olo 10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	270.707 L/min	Standard Error 4.515
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	263.134 L/min	Standard Error 4.092
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	271.071 L/min	Standard Error 4.289
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	280.836 L/min	Standard Error 4.582
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	293.986 L/min	Standard Error 4.517
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	283.326 L/min	Standard Error 4.452
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	291.503 L/min	Standard Error 4.64
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	290.283 L/min	Standard Error 4.556
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	264.808 L/min	Standard Error 4.211
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	263.757 L/min	Standard Error 3.921
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	295.008 L/min	Standard Error 4.685
T+O 1.25/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	293.039 L/min	Standard Error 4.531
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	268.772 L/min	Standard Error 4.168
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	294.713 L/min	Standard Error 4.502
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	296.641 L/min	Standard Error 4.652
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	267.013 L/min	Standard Error 4.064
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	288.427 L/min	Standard Error 4.422
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	298.394 L/min	Standard Error 4.609
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	276.004 L/min	Standard Error 4.262
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	293.466 L/min	Standard Error 4.526
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	293.617 L/min	Standard Error 4.488
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	287.502 L/min	Standard Error 4.55
T+O 2.5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	267.623 L/min	Standard Error 3.895
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 4:00 hr response	302.539 L/min	Standard Error 4.502
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:30 hr response	288.289 L/min	Standard Error 4.566
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 3:00 hr response	300.582 L/min	Standard Error 4.669
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:05 hr response	275.727 L/min	Standard Error 4.275
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 2:00 hr response	294.627 L/min	Standard Error 4.625
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 0:00 hr response	266.187 L/min	Standard Error 3.898
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -0:10 hr response	266.506 L/min	Standard Error 4.183
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 5:00 hr response	300.335 L/min	Standard Error 4.517
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint -1:00 hr response	266.913 L/min	Standard Error 4.067
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 1:00 hr response	288.585 L/min	Standard Error 4.437
T+O 5/10	Individual PEF Measurements at Each Time Point on Day 29	Timepoint 6:00 hr response	299.234 L/min	Standard Error 4.541

Secondary

Patients Global Rating

Adjusted means of the Global Rating of the patients' health (respiratory condition) on day 29. The score was evaluated on a 7-point scale : * 1 : very much better * 2 : much better * 3 : a little better * 4 : no change * 5 : a little worse * 6 : much worse * 7 : very much worse

Time frame: Day 29

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	Patients Global Rating	3.357 units on a scale	Standard Error 0.102
T+O 1.25/5	Patients Global Rating	3.135 units on a scale	Standard Error 0.102
T+O 2.5/5	Patients Global Rating	2.916 units on a scale	Standard Error 0.102
T+O 5/5	Patients Global Rating	3.208 units on a scale	Standard Error 0.104
Olo 10	Patients Global Rating	3.262 units on a scale	Standard Error 0.102
T+O 1.25/10	Patients Global Rating	2.880 units on a scale	Standard Error 0.103
T+O 2.5/10	Patients Global Rating	3.130 units on a scale	Standard Error 0.102
T+O 5/10	Patients Global Rating	2.936 units on a scale	Standard Error 0.102

95% CI: [-0.481, 0.037]Mixed Models Analysis

95% CI: [-0.7, -0.182]Mixed Models Analysis

95% CI: [-0.409, 0.111]Mixed Models Analysis

95% CI: [-0.478, 0.04]Mixed Models Analysis

95% CI: [-0.189, 0.335]Mixed Models Analysis

95% CI: [0.031, 0.553]Mixed Models Analysis

95% CI: [-0.641, -0.123]Mixed Models Analysis

95% CI: [-0.39, 0.127]Mixed Models Analysis

95% CI: [-0.585, -0.067]Mixed Models Analysis

95% CI: [-0.01, 0.511]Mixed Models Analysis

95% CI: [-0.202, 0.314]Mixed Models Analysis

95% CI: [-0.453, 0.065]Mixed Models Analysis

Secondary

PEF AUC 0-3h and AUC 0-6h Responses

Adjusted means of the Peak Expiratory Flow (PEF) AUC 0-3h and AUC 0-6h responses in Litres / minute (L/min) after 4 weeks of treatment, calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Olo 5	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-3h	25.542 L/min	Standard Error 4.19
Olo 5	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-6h	28.071 L/min	Standard Error 4.125
T+O 1.25/5	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-3h	44.301 L/min	Standard Error 4.202
T+O 1.25/5	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-6h	46.822 L/min	Standard Error 4.136
T+O 2.5/5	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-3h	50.698 L/min	Standard Error 4.167
T+O 2.5/5	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-6h	54.081 L/min	Standard Error 4.104
T+O 5/5	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-3h	55.346 L/min	Standard Error 4.234
T+O 5/5	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-6h	57.418 L/min	Standard Error 4.166
Olo 10	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-3h	29.713 L/min	Standard Error 4.183
Olo 10	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-6h	31.831 L/min	Standard Error 4.119
T+O 1.25/10	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-3h	48.032 L/min	Standard Error 4.218
T+O 1.25/10	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-6h	51.485 L/min	Standard Error 4.151
T+O 2.5/10	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-6h	54.593 L/min	Standard Error 4.127
T+O 2.5/10	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-3h	53.224 L/min	Standard Error 4.192
T+O 5/10	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-3h	52.531 L/min	Standard Error 4.205
T+O 5/10	PEF AUC 0-3h and AUC 0-6h Responses	AUC 0-6h	57.367 L/min	Standard Error 4.139

Comparison: AUC 0-3h95% CI: [10.533, 26.985]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [16.962, 33.351]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [21.526, 38.082]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-1.796, 14.592]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [2.721, 19.37]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-3.608, 12.903]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [10.068, 26.568]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [15.27, 31.752]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [14.543, 31.092]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-3.115, 13.5]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-3.719, 12.717]Mixed Models Analysis

Comparison: AUC 0-3h95% CI: [-8.941, 7.554]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [10.87, 26.632]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [18.158, 33.86]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [21.416, 37.278]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-0.592, 15.109]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [2.621, 18.571]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-4.572, 11.247]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [11.75, 27.558]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [14.866, 30.659]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [17.607, 33.464]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-4.852, 11.067]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-1.991, 13.754]Mixed Models Analysis

Comparison: AUC 0-6h95% CI: [-5.129, 10.675]Mixed Models Analysis

Secondary

PEF AUC 0-3h Response After the First Dose

Adjusted means of the Area under the curve from 0 to 3 h response in Litres / minutes of the peak expiratory flow after the first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	PEF AUC 0-3h Response After the First Dose	30.575 L/min	Standard Error 4.047
T+O 1.25/5	PEF AUC 0-3h Response After the First Dose	32.891 L/min	Standard Error 4.05
T+O 2.5/5	PEF AUC 0-3h Response After the First Dose	35.053 L/min	Standard Error 4.022
T+O 5/5	PEF AUC 0-3h Response After the First Dose	35.243 L/min	Standard Error 4.084
Olo 10	PEF AUC 0-3h Response After the First Dose	31.724 L/min	Standard Error 4.04
T+O 1.25/10	PEF AUC 0-3h Response After the First Dose	33.213 L/min	Standard Error 4.079
T+O 2.5/10	PEF AUC 0-3h Response After the First Dose	34.987 L/min	Standard Error 4.051
T+O 5/10	PEF AUC 0-3h Response After the First Dose	38.846 L/min	Standard Error 4.065

95% CI: [-6.268, 10.9]Mixed Models Analysis

95% CI: [-4.088, 13.044]Mixed Models Analysis

95% CI: [-3.978, 13.314]Mixed Models Analysis

95% CI: [-6.379, 10.702]Mixed Models Analysis

95% CI: [-6.326, 11.029]Mixed Models Analysis

95% CI: [-8.43, 8.81]Mixed Models Analysis

95% CI: [-7.136, 10.113]Mixed Models Analysis

95% CI: [-5.35, 11.875]Mixed Models Analysis

95% CI: [-1.535, 15.778]Mixed Models Analysis

95% CI: [-6.91, 10.458]Mixed Models Analysis

95% CI: [-2.97, 14.236]Mixed Models Analysis

95% CI: [-4.786, 12.504]Mixed Models Analysis

Secondary

PEF Peak 0-3h Response

Adjusted means of the peak expiratory flow from 0 to 3 hours (PEF peak 0-3h) response in L/min after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	PEF Peak 0-3h Response	46.010 L/min	Standard Error 4.566
T+O 1.25/5	PEF Peak 0-3h Response	64.693 L/min	Standard Error 4.581
T+O 2.5/5	PEF Peak 0-3h Response	69.610 L/min	Standard Error 4.538
T+O 5/5	PEF Peak 0-3h Response	76.108 L/min	Standard Error 4.62
Olo 10	PEF Peak 0-3h Response	49.025 L/min	Standard Error 4.557
T+O 1.25/10	PEF Peak 0-3h Response	66.767 L/min	Standard Error 4.6
T+O 2.5/10	PEF Peak 0-3h Response	73.140 L/min	Standard Error 4.569
T+O 5/10	PEF Peak 0-3h Response	74.120 L/min	Standard Error 4.584

95% CI: [9.161, 28.204]Mixed Models Analysis

95% CI: [14.116, 33.083]Mixed Models Analysis

95% CI: [20.517, 39.677]Mixed Models Analysis

95% CI: [-4.568, 14.402]Mixed Models Analysis

95% CI: [1.78, 21.05]Mixed Models Analysis

95% CI: [-3.057, 16.053]Mixed Models Analysis

95% CI: [8.194, 27.29]Mixed Models Analysis

95% CI: [14.58, 33.651]Mixed Models Analysis

95% CI: [15.52, 34.67]Mixed Models Analysis

95% CI: [-3.24, 15.986]Mixed Models Analysis

95% CI: [-2.161, 16.866]Mixed Models Analysis

95% CI: [-8.566, 10.525]Mixed Models Analysis

Secondary

PEF Peak 0-3h Response After the First Dose

Adjusted means of the Peak Expiratory flow from 0 to 3 hours response in L/min after the first dose of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	PEF Peak 0-3h Response After the First Dose	52.129 L/min	Standard Error 4.363
T+O 1.25/5	PEF Peak 0-3h Response After the First Dose	53.298 L/min	Standard Error 4.366
T+O 2.5/5	PEF Peak 0-3h Response After the First Dose	56.565 L/min	Standard Error 4.335
T+O 5/5	PEF Peak 0-3h Response After the First Dose	57.318 L/min	Standard Error 4.406
Olo 10	PEF Peak 0-3h Response After the First Dose	51.980 L/min	Standard Error 4.355
T+O 1.25/10	PEF Peak 0-3h Response After the First Dose	54.966 L/min	Standard Error 4.4
T+O 2.5/10	PEF Peak 0-3h Response After the First Dose	56.896 L/min	Standard Error 4.367
T+O 5/10	PEF Peak 0-3h Response After the First Dose	59.412 L/min	Standard Error 4.37

95% CI: [-8.36, 10.699]Mixed Models Analysis

95% CI: [-5.073, 13.945]Mixed Models Analysis

95% CI: [-4.407, 14.785]Mixed Models Analysis

95% CI: [-6.214, 12.747]Mixed Models Analysis

95% CI: [-5.61, 13.65]Mixed Models Analysis

95% CI: [-8.816, 10.322]Mixed Models Analysis

95% CI: [-6.589, 12.561]Mixed Models Analysis

95% CI: [-4.643, 14.475]Mixed Models Analysis

95% CI: [-2.154, 17.019]Mixed Models Analysis

95% CI: [-7.708, 11.568]Mixed Models Analysis

95% CI: [-5.085, 13.978]Mixed Models Analysis

95% CI: [-7.046, 12.079]Mixed Models Analysis

Secondary

Physicians Global Evaluation

Adjusted means of the Physicians Global Evaluation of the patient's respiratory condition on days 1 and 29. The score was evaluated on a 8-points scale : * Poor : 1,2 * Fair : 3,4 * Good : 5,6 * Excellent : 7,8

Time frame: Days 1 and 29

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Olo 5	Physicians Global Evaluation	Day 1	4.618 units on a scale	Standard Error 0.09
Olo 5	Physicians Global Evaluation	Day 29	4.985 units on a scale	Standard Error 0.093
T+O 1.25/5	Physicians Global Evaluation	Day 1	4.631 units on a scale	Standard Error 0.09
T+O 1.25/5	Physicians Global Evaluation	Day 29	5.146 units on a scale	Standard Error 0.091
T+O 2.5/5	Physicians Global Evaluation	Day 1	4.484 units on a scale	Standard Error 0.089
T+O 2.5/5	Physicians Global Evaluation	Day 29	5.248 units on a scale	Standard Error 0.091
T+O 5/5	Physicians Global Evaluation	Day 1	4.579 units on a scale	Standard Error 0.091
T+O 5/5	Physicians Global Evaluation	Day 29	5.070 units on a scale	Standard Error 0.094
Olo 10	Physicians Global Evaluation	Day 1	4.747 units on a scale	Standard Error 0.09
Olo 10	Physicians Global Evaluation	Day 29	5.109 units on a scale	Standard Error 0.092
T+O 1.25/10	Physicians Global Evaluation	Day 1	4.464 units on a scale	Standard Error 0.091
T+O 1.25/10	Physicians Global Evaluation	Day 29	5.280 units on a scale	Standard Error 0.093
T+O 2.5/10	Physicians Global Evaluation	Day 29	5.165 units on a scale	Standard Error 0.092
T+O 2.5/10	Physicians Global Evaluation	Day 1	4.634 units on a scale	Standard Error 0.09
T+O 5/10	Physicians Global Evaluation	Day 1	4.690 units on a scale	Standard Error 0.09
T+O 5/10	Physicians Global Evaluation	Day 29	5.227 units on a scale	Standard Error 0.092

Comparison: Day 195% CI: [-0.223, 0.25]Mixed Models Analysis

Comparison: Day 195% CI: [-0.37, 0.104]Mixed Models Analysis

Comparison: Day 195% CI: [-0.278, 0.199]Mixed Models Analysis

Comparison: Day 195% CI: [-0.382, 0.088]Mixed Models Analysis

Comparison: Day 195% CI: [-0.291, 0.186]Mixed Models Analysis

Comparison: Day 195% CI: [-0.144, 0.332]Mixed Models Analysis

Comparison: Day 195% CI: [-0.519, -0.045]Mixed Models Analysis

Comparison: Day 195% CI: [-0.35, 0.124]Mixed Models Analysis

Comparison: Day 195% CI: [-0.293, 0.18]Mixed Models Analysis

Comparison: Day 195% CI: [-0.069, 0.408]Mixed Models Analysis

Comparison: Day 195% CI: [-0.01, 0.461]Mixed Models Analysis

Comparison: Day 195% CI: [-0.18, 0.293]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.067, 0.387]Mixed Models Analysis

Comparison: Day 2995% CI: [0.034, 0.491]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.148, 0.316]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.124, 0.328]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.306, 0.154]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.408, 0.052]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.056, 0.4]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.171, 0.285]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.11, 0.346]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.345, 0.115]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.281, 0.173]Mixed Models Analysis

Comparison: Day 2995% CI: [-0.166, 0.289]Mixed Models Analysis

Secondary

Pulse Rate Recorded in Conjunction With Spirometry

Pulse rate recorded in conjunction with spirometry change from baseline at 30 minutes post-dose on day 29 in beats per minute (bpm).

Time frame: Baseline and 30 min post-dose on day 29

Population: TS which comprised all patients who were dispensed study medication, were documented to have taken at least 1 dose of investigational treatment and had available data for pulse rate at baseline and day 29.

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	Pulse Rate Recorded in Conjunction With Spirometry	-2.4 bpm	Standard Deviation 10.4
T+O 1.25/5	Pulse Rate Recorded in Conjunction With Spirometry	-2.8 bpm	Standard Deviation 10.3
T+O 2.5/5	Pulse Rate Recorded in Conjunction With Spirometry	-3.1 bpm	Standard Deviation 10.3
T+O 5/5	Pulse Rate Recorded in Conjunction With Spirometry	-1.8 bpm	Standard Deviation 9.5
Olo 10	Pulse Rate Recorded in Conjunction With Spirometry	-2.1 bpm	Standard Deviation 8.5
T+O 1.25/10	Pulse Rate Recorded in Conjunction With Spirometry	-3.6 bpm	Standard Deviation 9.6
T+O 2.5/10	Pulse Rate Recorded in Conjunction With Spirometry	-2.4 bpm	Standard Deviation 10.5
T+O 5/10	Pulse Rate Recorded in Conjunction With Spirometry	-1.0 bpm	Standard Deviation 10.2

Secondary

Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry

Systolic and diastolic blood pressure recorded in conjunction with spirometry change from baseline on day 29 in millimetres of mercury (mmHg).

Time frame: Baseline and 30 min post-dose on day 29

Arm	Measure	Group	Value (MEAN)	Dispersion
Olo 5	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Systolic blood pressure	-7.2 mmHg	Standard Deviation 15
Olo 5	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Diastolic blood pressure	-3.8 mmHg	Standard Deviation 9.1
T+O 1.25/5	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Systolic blood pressure	-6.0 mmHg	Standard Deviation 12.8
T+O 1.25/5	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Diastolic blood pressure	-2.8 mmHg	Standard Deviation 8.6
T+O 2.5/5	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Systolic blood pressure	-5.6 mmHg	Standard Deviation 15
T+O 2.5/5	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Diastolic blood pressure	-2.5 mmHg	Standard Deviation 9.8
T+O 5/5	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Systolic blood pressure	-4.8 mmHg	Standard Deviation 13.9
T+O 5/5	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Diastolic blood pressure	-3.0 mmHg	Standard Deviation 9.8
Olo 10	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Systolic blood pressure	-3.4 mmHg	Standard Deviation 14.7
Olo 10	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Diastolic blood pressure	-3.0 mmHg	Standard Deviation 8.6
T+O 1.25/10	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Systolic blood pressure	-5.5 mmHg	Standard Deviation 15.2
T+O 1.25/10	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Diastolic blood pressure	-3.0 mmHg	Standard Deviation 9.1
T+O 2.5/10	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Diastolic blood pressure	-2.5 mmHg	Standard Deviation 9.7
T+O 2.5/10	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Systolic blood pressure	-3.8 mmHg	Standard Deviation 14.2
T+O 5/10	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Systolic blood pressure	-2.2 mmHg	Standard Deviation 13
T+O 5/10	Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry	Diastolic blood pressure	-0.4 mmHg	Standard Deviation 9.2

Secondary

Trough Forced Vital Capacity (FVC) Response

Adjusted means of trough FVC (forced vital capacity) response \[L\] after 4 weeks treatment. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.

Time frame: Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29

Population: FAS which included all patients who were dispensed study medication and who provided baseline and at least 1 on-treatment efficacy value for the primary endpoint after 4 weeks on treatment.

Arm	Measure	Value (MEAN)	Dispersion
Olo 5	Trough Forced Vital Capacity (FVC) Response	0.114 Litres	Standard Error 0.029
T+O 1.25/5	Trough Forced Vital Capacity (FVC) Response	0.214 Litres	Standard Error 0.029
T+O 2.5/5	Trough Forced Vital Capacity (FVC) Response	0.234 Litres	Standard Error 0.029
T+O 5/5	Trough Forced Vital Capacity (FVC) Response	0.215 Litres	Standard Error 0.029
Olo 10	Trough Forced Vital Capacity (FVC) Response	0.122 Litres	Standard Error 0.029
T+O 1.25/10	Trough Forced Vital Capacity (FVC) Response	0.253 Litres	Standard Error 0.029
T+O 2.5/10	Trough Forced Vital Capacity (FVC) Response	0.253 Litres	Standard Error 0.029
T+O 5/10	Trough Forced Vital Capacity (FVC) Response	0.249 Litres	Standard Error 0.029

95% CI: [0.04, 0.159]Mixed Models Analysis

95% CI: [0.061, 0.179]Mixed Models Analysis

95% CI: [0.041, 0.16]Mixed Models Analysis

95% CI: [-0.039, 0.079]Mixed Models Analysis

95% CI: [-0.059, 0.061]Mixed Models Analysis

95% CI: [-0.079, 0.04]Mixed Models Analysis

95% CI: [0.071, 0.19]Mixed Models Analysis

95% CI: [0.072, 0.191]Mixed Models Analysis

95% CI: [0.067, 0.187]Mixed Models Analysis

95% CI: [-0.059, 0.061]Mixed Models Analysis

95% CI: [-0.063, 0.056]Mixed Models Analysis

95% CI: [-0.064, 0.055]Mixed Models Analysis

Secondary

Weekly Mean Number of Puffs of Rescue Medication Used Per Day

Adjusted means of the weekly mean number of puffs of rescue medication during the whole day : the rescue medication was a salbutamol \[albuterol\] dose (100 mcg per puff).

Time frame: Weeks 1 and 4

Population: FAS

Arm	Measure	Group	Value (MEAN)	Dispersion
Olo 5	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 1	1.511 number of puffs per day	Standard Error 0.146
Olo 5	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 4	1.391 number of puffs per day	Standard Error 0.164
T+O 1.25/5	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 1	1.298 number of puffs per day	Standard Error 0.145
T+O 1.25/5	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 4	1.502 number of puffs per day	Standard Error 0.163
T+O 2.5/5	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 1	1.191 number of puffs per day	Standard Error 0.147
T+O 2.5/5	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 4	1.299 number of puffs per day	Standard Error 0.163
T+O 5/5	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 1	1.446 number of puffs per day	Standard Error 0.147
T+O 5/5	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 4	1.444 number of puffs per day	Standard Error 0.164
Olo 10	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 1	1.423 number of puffs per day	Standard Error 0.145
Olo 10	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 4	1.561 number of puffs per day	Standard Error 0.162
T+O 1.25/10	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 1	1.465 number of puffs per day	Standard Error 0.147
T+O 1.25/10	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 4	1.344 number of puffs per day	Standard Error 0.165
T+O 2.5/10	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 4	1.198 number of puffs per day	Standard Error 0.164
T+O 2.5/10	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 1	1.172 number of puffs per day	Standard Error 0.146
T+O 5/10	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 1	1.244 number of puffs per day	Standard Error 0.146
T+O 5/10	Weekly Mean Number of Puffs of Rescue Medication Used Per Day	Week 4	1.315 number of puffs per day	Standard Error 0.163

Comparison: Week 195% CI: [-0.523, 0.099]Mixed Models Analysis

Comparison: Week 195% CI: [-0.634, -0.004]Mixed Models Analysis

Comparison: Week 195% CI: [-0.379, 0.249]Mixed Models Analysis

Comparison: Week 195% CI: [-0.42, 0.206]Mixed Models Analysis

Comparison: Week 195% CI: [-0.168, 0.462]Mixed Models Analysis

Comparison: Week 195% CI: [-0.062, 0.571]Mixed Models Analysis

Comparison: Week 195% CI: [-0.271, 0.355]Mixed Models Analysis

Comparison: Week 195% CI: [-0.564, 0.062]Mixed Models Analysis

Comparison: Week 195% CI: [-0.492, 0.135]Mixed Models Analysis

Comparison: Week 195% CI: [-0.611, 0.024]Mixed Models Analysis

Comparison: Week 195% CI: [-0.533, 0.092]Mixed Models Analysis

Comparison: Week 195% CI: [-0.242, 0.388]Mixed Models Analysis

Comparison: Week 495% CI: [-0.241, 0.462]Mixed Models Analysis

Comparison: Week 495% CI: [-0.445, 0.261]Mixed Models Analysis

Comparison: Week 495% CI: [-0.301, 0.406]Mixed Models Analysis

Comparison: Week 495% CI: [-0.555, 0.15]Mixed Models Analysis

Comparison: Week 495% CI: [-0.411, 0.296]Mixed Models Analysis

Comparison: Week 495% CI: [-0.208, 0.496]Mixed Models Analysis

Comparison: Week 495% CI: [-0.568, 0.135]Mixed Models Analysis

Comparison: Week 495% CI: [-0.714, -0.012]Mixed Models Analysis

Comparison: Week 495% CI: [-0.598, 0.106]Mixed Models Analysis

Comparison: Week 495% CI: [-0.503, 0.21]Mixed Models Analysis

Comparison: Week 495% CI: [-0.379, 0.321]Mixed Models Analysis

Comparison: Week 495% CI: [-0.235, 0.47]Mixed Models Analysis

Source: ClinicalTrials.gov · Data processed: Mar 4, 2026

Determining Optimal Free Dose Combination of Tiotropium Bromide and BI 1744 CL in Chronic Obstructive Pulmonary Disease (COPD)

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Trough FEV1 Response

FEV1 AUC 0-3h and FEV1 AUC 0-6h Response

FEV1 AUC 0-3h Response After the First Dose

FEV1 Peak 0-3h Response

FEV1 Peak 0-3h Response After the First Dose

FVC AUC 0-3h and FEV1 AUC 0-6h Responses

FVC AUC 0-3h Response After First Dose

FVC Peak 0-3h Response

FVC Peak 0-3h Response After the First Dose

Individual FEV1 Measurements at Each Time Point on Day 29

Individual FVC Measurements at Each Time Point on Day 29

Individual PEF Measurements at Each Time Point on Day 29

Patients Global Rating

PEF AUC 0-3h and AUC 0-6h Responses

PEF AUC 0-3h Response After the First Dose

PEF Peak 0-3h Response

PEF Peak 0-3h Response After the First Dose

Physicians Global Evaluation

Pulse Rate Recorded in Conjunction With Spirometry

Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry

Trough Forced Vital Capacity (FVC) Response

Weekly Mean Number of Puffs of Rescue Medication Used Per Day