Trial Outcomes & Findings for Fixed Dose Combination Versus Free Combination of Tiotropium and Olodaterol in COPD (NCT NCT02683109)

NCT ID: NCT02683109

Last Updated: 2018-08-17

Results Overview

This outcome measure presents FEV1 after 28 days of treatment (measurement on Day 29). Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), and was measured at 24 hours (+/- 10 minutes) after trial medication administration at Visit 5. The FEV1 measurement at Visit 4, which was 24 hours after the last open-label run-in treatment intake and 15 minutes before the first double-blind study drug intake was the baseline measurement.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 221 participants
• Primary outcome timeframe: Day 29
• Results posted on: 2018-08-17

Participant Flow

Definition: Open-Label Treated Set (OLTS): This patient set includes all patients who signed the informed consent and were dispensed open-label study medication during the run-in period prior to randomisation and were documented to have taken any dose of this medication.

Definition: Randomised Set (RS): This patient set is nested within the OLTS and includes all patients who signed the informed consent form and were also randomised, regardless of whether the patient was treated with study medication or not.

Participant milestones

Measure	T+O 5/5 The subjects were administered Tiotropium (T) + Olodaterol (O) Fixed Dose Combination (FDC) solution for inhalation 2.5 μg/2.5 μg per actuation, 2 inhalations orally once daily via RESPIMAT® inhaler. Placebo matching Tiotropium solution was administered 2 inhalations once daily via RESPIMAT® inhaler.	T 5/O 5 The subjects were administered Tiotropium solution for inhalation, 2.5 μg per actuation + Olodaterol solution for inhalation, 2.5 μg per actuation as a free combination. Two inhalations were administered once daily (a.m. dosing) via RESPIMAT® inhaler for both Tiotropium and Olodaterol.
Overall Study STARTED	110	111
Overall Study COMPLETED	109	111
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	T+O 5/5 The subjects were administered Tiotropium (T) + Olodaterol (O) Fixed Dose Combination (FDC) solution for inhalation 2.5 μg/2.5 μg per actuation, 2 inhalations orally once daily via RESPIMAT® inhaler. Placebo matching Tiotropium solution was administered 2 inhalations once daily via RESPIMAT® inhaler.	T 5/O 5 The subjects were administered Tiotropium solution for inhalation, 2.5 μg per actuation + Olodaterol solution for inhalation, 2.5 μg per actuation as a free combination. Two inhalations were administered once daily (a.m. dosing) via RESPIMAT® inhaler for both Tiotropium and Olodaterol.
Overall Study Adverse Event	1	0

Baseline Characteristics

Fixed Dose Combination Versus Free Combination of Tiotropium and Olodaterol in COPD

Baseline characteristics by cohort

Measure	T+O 5/5 n=110 Participants The subjects were administered Tiotropium (T) + Olodaterol (O) Fixed Dose Combination (FDC) solution for inhalation 2.5 μg/2.5 μg per actuation, 2 inhalations orally once daily via RESPIMAT® inhaler. Placebo matching Tiotropium solution was administered 2 inhalations once daily via RESPIMAT® inhaler.	T 5/O 5 n=111 Participants The subjects were administered Tiotropium solution for inhalation, 2.5 μg per actuation + Olodaterol solution for inhalation, 2.5 μg per actuation as a free combination. Two inhalations were administered once daily (a.m. dosing) via RESPIMAT® inhaler for both Tiotropium and Olodaterol.	Total n=221 Participants Total of all reporting groups
Age, Continuous	66.5 Years STANDARD_DEVIATION 7.1 • n=5 Participants	66.5 Years STANDARD_DEVIATION 6.4 • n=7 Participants	66.5 Years STANDARD_DEVIATION 6.8 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	30 Participants n=7 Participants	63 Participants n=5 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	81 Participants n=7 Participants	158 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 29

Population: Full Analysis Set (FAS): This patient set is nested within the TS and includes patients who had a baseline measurement and at least one post-baseline measurement for the primary endpoint.

This outcome measure presents FEV1 after 28 days of treatment (measurement on Day 29). Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), and was measured at 24 hours (+/- 10 minutes) after trial medication administration at Visit 5.

The FEV1 measurement at Visit 4, which was 24 hours after the last open-label run-in treatment intake and 15 minutes before the first double-blind study drug intake was the baseline measurement.

Outcome measures

Measure	T+O 5/5 n=108 Participants The subjects were administered Tiotropium (T) + Olodaterol (O) Fixed Dose Combination (FDC) solution for inhalation 2.5 μg/2.5 μg per actuation, 2 inhalations orally once daily via RESPIMAT® inhaler. Placebo matching Tiotropium solution was administered 2 inhalations once daily via RESPIMAT® inhaler.	T 5/O 5 n=108 Participants The subjects were administered Tiotropium solution for inhalation, 2.5 μg per actuation + Olodaterol solution for inhalation, 2.5 μg per actuation as a free combination. Two inhalations were administered once daily (a.m. dosing) via RESPIMAT® inhaler for both Tiotropium and Olodaterol.
Trough Forced Expiratory Volume in 1 Second (FEV1) (in Liter) After 28 Days of Treatment	1.422 Liter Standard Error 0.016	1.399 Liter Standard Error 0.016

SECONDARY outcome

Timeframe: Day 29

Population: FAS.

This outcome measure presents trough FVC after 28 days of treatment (measurement on Day 29).

The FVC measurement at Visit 4, which was 24 hours after the last open-label run-in treatment intake and 15 minutes before the first double-blind study drug intake was the baseline measurement for FVC.

Outcome measures

Measure	T+O 5/5 n=108 Participants The subjects were administered Tiotropium (T) + Olodaterol (O) Fixed Dose Combination (FDC) solution for inhalation 2.5 μg/2.5 μg per actuation, 2 inhalations orally once daily via RESPIMAT® inhaler. Placebo matching Tiotropium solution was administered 2 inhalations once daily via RESPIMAT® inhaler.	T 5/O 5 n=108 Participants The subjects were administered Tiotropium solution for inhalation, 2.5 μg per actuation + Olodaterol solution for inhalation, 2.5 μg per actuation as a free combination. Two inhalations were administered once daily (a.m. dosing) via RESPIMAT® inhaler for both Tiotropium and Olodaterol.
Trough Forced Vital Capacity (FVC) (in Liter) After 28 Days of Treatment	3.126 Liter Standard Error 0.024	3.121 Liter Standard Error 0.024

SECONDARY outcome

Timeframe: Day 28

Population: FAS. One patient in the T 5/O 5 free combination group had missing data for the CAT questionnaire.

This outcome measure presents COPD assessment test score on Day 28. The COPD Assessment Test™ is a short 8-item questionnaire for assessment and monitoring of COPD health status in routine practice. Its scale is 0-40 (high score = poor health).

The CAT measurement on Visit 4 prior to the first dose of double-blind study drug was the baseline for CAT.

Outcome measures

Measure	T+O 5/5 n=108 Participants The subjects were administered Tiotropium (T) + Olodaterol (O) Fixed Dose Combination (FDC) solution for inhalation 2.5 μg/2.5 μg per actuation, 2 inhalations orally once daily via RESPIMAT® inhaler. Placebo matching Tiotropium solution was administered 2 inhalations once daily via RESPIMAT® inhaler.	T 5/O 5 n=107 Participants The subjects were administered Tiotropium solution for inhalation, 2.5 μg per actuation + Olodaterol solution for inhalation, 2.5 μg per actuation as a free combination. Two inhalations were administered once daily (a.m. dosing) via RESPIMAT® inhaler for both Tiotropium and Olodaterol.
Chronic Obstructive Pulmonary Disease (COPD) Assessment Test™ (CAT) Score on Day 28	15.423 Score on scale Standard Error 0.377	15.750 Score on scale Standard Error 0.379

Adverse Events

T+O 5/5

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

T 5/O 5

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Total

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	T+O 5/5 n=110 participants at risk The subjects were administered Tiotropium (T) + Olodaterol (O) Fixed Dose Combination (FDC) solution for inhalation 2.5 μg/2.5 μg per actuation, 2 inhalations orally once daily via RESPIMAT® inhaler. Placebo matching Tiotropium solution was administered 2 inhalations once daily via RESPIMAT® inhaler.	T 5/O 5 n=111 participants at risk The subjects were administered Tiotropium solution for inhalation, 2.5 μg per actuation + Olodaterol solution for inhalation, 2.5 μg per actuation as a free combination. Two inhalations were administered once daily (a.m. dosing) via RESPIMAT® inhaler for both Tiotropium and Olodaterol.	Total n=221 participants at risk The total number of subjects who were administered T+O 5/5 or T 5/O 5.
Cardiac disorders Cardiac failure	0.91% 1/110 • From first drug administration until 28 days after last drug administration, up to 49 days.	0.00% 0/111 • From first drug administration until 28 days after last drug administration, up to 49 days.	0.45% 1/221 • From first drug administration until 28 days after last drug administration, up to 49 days.
Cardiac disorders Left ventricular failure	0.00% 0/110 • From first drug administration until 28 days after last drug administration, up to 49 days.	0.90% 1/111 • From first drug administration until 28 days after last drug administration, up to 49 days.	0.45% 1/221 • From first drug administration until 28 days after last drug administration, up to 49 days.
Vascular disorders Deep vein thrombosis	0.00% 0/110 • From first drug administration until 28 days after last drug administration, up to 49 days.	0.90% 1/111 • From first drug administration until 28 days after last drug administration, up to 49 days.	0.45% 1/221 • From first drug administration until 28 days after last drug administration, up to 49 days.

Other adverse events

Measure	T+O 5/5 n=110 participants at risk The subjects were administered Tiotropium (T) + Olodaterol (O) Fixed Dose Combination (FDC) solution for inhalation 2.5 μg/2.5 μg per actuation, 2 inhalations orally once daily via RESPIMAT® inhaler. Placebo matching Tiotropium solution was administered 2 inhalations once daily via RESPIMAT® inhaler.	T 5/O 5 n=111 participants at risk The subjects were administered Tiotropium solution for inhalation, 2.5 μg per actuation + Olodaterol solution for inhalation, 2.5 μg per actuation as a free combination. Two inhalations were administered once daily (a.m. dosing) via RESPIMAT® inhaler for both Tiotropium and Olodaterol.	Total n=221 participants at risk The total number of subjects who were administered T+O 5/5 or T 5/O 5.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	8.2% 9/110 • From first drug administration until 28 days after last drug administration, up to 49 days.	8.1% 9/111 • From first drug administration until 28 days after last drug administration, up to 49 days.	8.1% 18/221 • From first drug administration until 28 days after last drug administration, up to 49 days.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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.
• Publication restrictions are in place

Restriction type: OTHER