Trial Outcomes & Findings for Japan Long-term Safety for Tiotropium Plus Olodaterol (NCT NCT01536262)

NCT ID: NCT01536262

Last Updated: 2015-07-15

Results Overview

Number (%) of patients with drug-related Adverse Events (AEs).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

122 participants

Primary outcome timeframe

From first drug administration until 21 days after the last administration, upto 392 days

Results posted on

2015-07-15

Participant Flow

This study was a 52-week multi-centre, randomised, double-blind and parallel-group design.

Participant milestones

Participant milestones
Measure	Olodaterol (5 μg) Olodaterol solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (2.5 / 5 μg) Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (5 / 5 μg) Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.
Overall Study STARTED	41	40	41
Overall Study COMPLETED	33	38	39
Overall Study NOT COMPLETED	8	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Olodaterol (5 μg) Olodaterol solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (2.5 / 5 μg) Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (5 / 5 μg) Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.
Overall Study Adverse Event	6	1	2
Overall Study Withdrawal by Subject	1	1	0
Overall Study Other than stated above	1	0	0

Baseline Characteristics

Japan Long-term Safety for Tiotropium Plus Olodaterol

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olodaterol (5 μg) n=41 Participants Olodaterol solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (2.5 / 5 μg) n=40 Participants Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (5 / 5 μg) n=41 Participants Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Total n=122 Participants Total of all reporting groups
Age, Continuous	71.5 years STANDARD_DEVIATION 7.2 • n=5 Participants	70.0 years STANDARD_DEVIATION 7.5 • n=7 Participants	68.1 years STANDARD_DEVIATION 7.1 • n=5 Participants	69.9 years STANDARD_DEVIATION 7.3 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	39 Participants n=7 Participants	38 Participants n=5 Participants	117 Participants n=4 Participants

PRIMARY outcome

Timeframe: From first drug administration until 21 days after the last administration, upto 392 days

Population: Treated set: This patient set included all patients who received at least 1 dose of treatment.

Number (%) of patients with drug-related Adverse Events (AEs).

Outcome measures

Outcome measures
Measure	Olodaterol (5 μg) n=41 Participants Olodaterol solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (2.5 / 5 μg) n=40 Participants Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (5 / 5 μg) n=41 Participants Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.
Number (%) of Patients With Drug-related AEs	4.9 percentage of participants	5.0 percentage of participants	7.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline and 1 h, 10 min pre-dose and 30 min, 1 h, 2 h, 3 h post-dose after 52 weeks

Population: Full analysis set (FAS): This patient set included all randomised patients who received at least 1 dose of treatment and had both non-missing baseline and at least 1 non-missing post-baseline efficacy measurement. Assignment to FAS was done after implementation of any data handling rules which set measurements to missing.

Forced Expiratory Volume in 1 second Area Under Curve (AUC0-3h) response. FEV1 AUC0-3h was calculated using the trapezoidal rule, divided by the duration (3 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. Note: The Mean presented is the unadjusted mean.

Outcome measures

Outcome measures
Measure	Olodaterol (5 μg) n=34 Participants Olodaterol solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (2.5 / 5 μg) n=39 Participants Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (5 / 5 μg) n=39 Participants Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.
FEV1 AUC0-3h Response	0.132 L Standard Error 0.030	0.260 L Standard Error 0.031	0.237 L Standard Error 0.024

SECONDARY outcome

Timeframe: Baseline and 1 h, 10 min pre-dose after 52 weeks

Population: Full analysis set (FAS)

Trough Forced Expiratory Volume in 1 second Response. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements after 52 weeks. 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. Note: The Mean presented is the unadjusted mean.

Outcome measures

Outcome measures
Measure	Olodaterol (5 μg) n=34 Participants Olodaterol solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (2.5 / 5 μg) n=39 Participants Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (5 / 5 μg) n=39 Participants Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.
Trough FEV1 Response	0.075 L Standard Error 0.027	0.168 L Standard Error 0.031	0.143 L Standard Error 0.025

Adverse Events

Olodaterol (5 μg)

Serious events: 5 serious events

Other events: 21 other events

Deaths: 0 deaths

Tiotropium + Olodaterol (2.5 / 5 μg)

Serious events: 6 serious events

Other events: 20 other events

Deaths: 0 deaths

Tiotropium + Olodaterol (5 / 5 μg)

Serious events: 3 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Olodaterol (5 μg) n=41 participants at risk Olodaterol solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (2.5 / 5 μg) n=40 participants at risk Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (5 / 5 μg) n=41 participants at risk Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.
Cardiac disorders Acute myocardial infarction	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.	2.5% 1/40 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Cardiac disorders Cardiac failure acute	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/40 • From first drug administration until 21 days after the last administration, upto 392 days.	2.4% 1/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Cardiac disorders Cardiac failure chronic	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/40 • From first drug administration until 21 days after the last administration, upto 392 days.	2.4% 1/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Eye disorders Cataract	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.	2.5% 1/40 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Hepatobiliary disorders Bile duct stone	2.4% 1/41 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/40 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Infections and infestations Gastroenteritis	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.	2.5% 1/40 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Infections and infestations Pneumonia bacterial	2.4% 1/41 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/40 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	2.4% 1/41 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/40 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	4.9% 2/41 • From first drug administration until 21 days after the last administration, upto 392 days.	7.5% 3/40 • From first drug administration until 21 days after the last administration, upto 392 days.	4.9% 2/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	2.4% 1/41 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/40 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.	2.5% 1/40 • From first drug administration until 21 days after the last administration, upto 392 days.	0.00% 0/41 • From first drug administration until 21 days after the last administration, upto 392 days.

Other adverse events

Other adverse events
Measure	Olodaterol (5 μg) n=41 participants at risk Olodaterol solution for inhalation - RESPIMAT: 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (2.5 / 5 μg) n=40 participants at risk Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.	Tiotropium + Olodaterol (5 / 5 μg) n=41 participants at risk Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT : 2 Oral inhalation once daily in the morning up to 52-week treatment period.
Infections and infestations Pharyngitis	2.4% 1/41 • From first drug administration until 21 days after the last administration, upto 392 days.	7.5% 3/40 • From first drug administration until 21 days after the last administration, upto 392 days.	4.9% 2/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Gastrointestinal disorders Constipation	7.3% 3/41 • From first drug administration until 21 days after the last administration, upto 392 days.	2.5% 1/40 • From first drug administration until 21 days after the last administration, upto 392 days.	9.8% 4/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Infections and infestations Bronchitis	7.3% 3/41 • From first drug administration until 21 days after the last administration, upto 392 days.	12.5% 5/40 • From first drug administration until 21 days after the last administration, upto 392 days.	14.6% 6/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Infections and infestations Nasopharyngitis	41.5% 17/41 • From first drug administration until 21 days after the last administration, upto 392 days.	27.5% 11/40 • From first drug administration until 21 days after the last administration, upto 392 days.	26.8% 11/41 • From first drug administration until 21 days after the last administration, upto 392 days.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	9.8% 4/41 • From first drug administration until 21 days after the last administration, upto 392 days.	10.0% 4/40 • From first drug administration until 21 days after the last administration, upto 392 days.	17.1% 7/41 • From first drug administration until 21 days after the last administration, upto 392 days.

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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Restriction type: OTHER