Long-term Use of Spiolto Respimat in Japanese Patients With Chronic Obstructive Pulmonary Disease

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02850978
• Collaborator: (none)
• Enrollment: 1,335
• Location: 1
• Actual Duration (Months): 27.2
• Patients Per Site Per Month: 49

Study Details

Study Description

Brief Summary

Study to assess the long-term safety and effectiveness of Spiolto in Japanese patients with Chronic Obstructive Pulmonary Disease (COPD) in real-world setting

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Spiolto

Study Design

• Study Type: Observational
• Actual Enrollment: 1335 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Post-marketing Surveillance (PMS) on Long-term Use of Tiotropium+Olodaterol Fixed Dose Combination (Tio+Olo FDC) 5µg/5µg in Patients With Chronic Obstructive Pulmonary Disease (Chronic Bronchitis, Emphysema) in Japan
• Actual Study Start Date: Aug 23, 2016
• Actual Primary Completion Date: Oct 30, 2018
• Actual Study Completion Date: Nov 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Spiolto Patient with COPD to received Spiolto	Drug: Spiolto

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Drug Reactions [From the first drug administration until 21 days after the last drug administration, up to approximately 82 weeks.]

   Percentage of participants with adverse drug reactions (ADR). An adverse drug reaction (ADR) is defined as an adverse event (AE) for which either the investigator or the sponsor (or both) assess the causal relationship to Spiolto® Respimat® as "Yes".

Secondary Outcome Measures

1. Change of COPD Assessment Test (CAT) Score From Baseline to Week 12 [Baseline and Week 12]

   The COPD Assessment Test™ (CAT) 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 questionnaire has the advantage of a reduced number of items and could be used to assess the effects of inhaled therapies. The CAT score was the sum of the values corresponding to the answers to the eight questions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Patients who have been diagnosed with chronic obstructive pulmonary disease (chronic bronchitis, emphysema) by physician and need relief of various symptoms associated with Long Acting Beta2 Agonist (LABA) or Long Acting Muscarinic Antagonist (LAMA).

• Patients who are prescribed Tio+Olo FDC 5µg/5µg for the first time

Exclusion criteria:

• Patients who have been registered once in this study (i.e., re-entry of patients is not allowed).

• Patients who are participating in a registry or clinical trial.

• Patients who have a contraindication to Tio+Olo FDC 5µg/5µg defined in the package insert for Tio+Olo FDC 5µg/5µg.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Multiple Locations		Japan

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 29, 2018
• Study Protocol - May 10, 2016

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02850978
• Other Study ID Numbers: 1237.34
• First Posted: Aug 1, 2016
• Last Update Posted: Dec 6, 2019
• Last Verified: Nov 1, 2019

• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Recruitment Details	This was an observational study based on newly collected data under real-world practice in participants diagnosed with chronic obstructive pulmonary disease (COPD) (chronic bronchitis, emphysema) in Japan.
Pre-assignment Detail	This non-randomized, post marketing surveillance (PMS) was a prospective study using a continuous investigation system. No specific criteria (e.g. demographic, baseline, concomitant drug in use) were defined for participant enrollment. Participants were enrolled from August 2016 to August 2017.

Arm/Group Title	Spiolto®
Arm/Group Description	Participants suffering from COPD were treated with a Fixed Dose Combination (FDC) of Tiotropium (Tio) 5 microgram (μg)/ + Olodaterol (Olo) 5 μg; solution for oral inhalation via Respimat® inhaler once daily, for 52 weeks or until discontinuation of administration.
Period Title: Overall Study
STARTED	1335
Case Report Form (CRF) Collected	1308
Treated	1308
COMPLETED	909
NOT COMPLETED	426

Baseline Characteristics

Arm/Group Title	Spiolto®
Arm/Group Description	Participants suffering from COPD were treated with a Fixed Dose Combination (FDC) of Tiotropium (Tio) 5 microgram (μg)/ + Olodaterol (Olo) 5 μg; solution for oral inhalation via Respimat® inhaler once daily, for 52 weeks or until discontinuation of administration.
Overall Participants	1273
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	73.3 (9.1)
Sex: Female, Male (Count of Participants)
Female	206 16.2%
Male	1067 83.8%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Drug Reactions
Description	Percentage of participants with adverse drug reactions (ADR). An adverse drug reaction (ADR) is defined as an adverse event (AE) for which either the investigator or the sponsor (or both) assess the causal relationship to Spiolto® Respimat® as "Yes".
Time Frame	From the first drug administration until 21 days after the last drug administration, up to approximately 82 weeks.

Outcome Measure Data

Analysis Population Description

Safety set: This patient set includes all patients who were documented to have taken at least one dose of Spiolto® Respimat® excluding no visit after Spiolto® Respimat® administration.

Arm/Group Title	Spiolto®
Arm/Group Description	Participants suffering from COPD were treated with a Fixed Dose Combination (FDC) of Tiotropium (Tio) 5 microgram (μg)/ + Olodaterol (Olo) 5 μg; solution for oral inhalation via Respimat® inhaler once daily, for 52 weeks or until discontinuation of administration.
Measure Participants	1273
Number [Percentage of participants (%)]	3.93 0.3%

2. Secondary Outcome

Title	Change of COPD Assessment Test (CAT) Score From Baseline to Week 12
Description	The COPD Assessment Test™ (CAT) 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 questionnaire has the advantage of a reduced number of items and could be used to assess the effects of inhaled therapies. The CAT score was the sum of the values corresponding to the answers to the eight questions.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Effectiveness set: The effectiveness set included all patients in the safety set except for those patients who had no any values of CAT, Forced Expiratory Volume in one second (FEV1) and Forced Vital Capacity (FVC) after Spiolto® Respimat® administration.

Arm/Group Title	Spiolto®
Arm/Group Description	Participants suffering from COPD were treated with a Fixed Dose Combination (FDC) of Tiotropium (Tio) 5 microgram (μg)/ + Olodaterol (Olo) 5 μg; solution for oral inhalation via Respimat® inhaler once daily, for 52 weeks or until discontinuation of administration.
Measure Participants	1255
Mean (Standard Deviation) [Unit on a scale]	-3.7 (7.1)

Adverse Events

Time Frame	From the first drug administration until 21 days after the last drug administration, up to approximately 82 weeks.
Arm/Group Title	Spiolto®
Arm/Group Description	Participants suffering from COPD were treated with a Fixed Dose Combination (FDC) of Tiotropium (Tio) 5 microgram (μg)/ + Olodaterol (Olo) 5 μg; solution for oral inhalation via Respimat® inhaler once daily, for 52 weeks or until discontinuation of administration.
All Cause Mortality
	Spiolto®
	Affected / at Risk (%)	# Events
Total	38/1273 (3%)
Serious Adverse Events
	Spiolto®
	Affected / at Risk (%)	# Events
Total	94/1273 (7.4%)
Blood and lymphatic system disorders
Anaemia	2/1273 (0.2%)
Cardiac disorders
Cardiac failure	5/1273 (0.4%)
Cardiac failure congestive	3/1273 (0.2%)
Cardio-respiratory arrest	2/1273 (0.2%)
Acute myocardial infarction	1/1273 (0.1%)
Angina pectoris	1/1273 (0.1%)
Atrioventricular block second degree	1/1273 (0.1%)
Cardiac arrest	1/1273 (0.1%)
Cardiac failure acute	1/1273 (0.1%)
Cardiac failure chronic	1/1273 (0.1%)
Cardiovascular disorder	1/1273 (0.1%)
Pericarditis	1/1273 (0.1%)
Right ventricular failure	1/1273 (0.1%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula	1/1273 (0.1%)
Endocrine disorders
Adrenocortical insufficiency acute	1/1273 (0.1%)
Thyrotoxic crisis	1/1273 (0.1%)
Gastrointestinal disorders
Colitis ulcerative	1/1273 (0.1%)
Gastric ulcer	1/1273 (0.1%)
Gastric ulcer haemorrhage	1/1273 (0.1%)
Ileus	1/1273 (0.1%)
General disorders
Death	4/1273 (0.3%)
Sudden death	2/1273 (0.2%)
Pyrexia	1/1273 (0.1%)
Hepatobiliary disorders
Bile duct stone	1/1273 (0.1%)
Cholangitis	1/1273 (0.1%)
Cholecystitis chronic	1/1273 (0.1%)
Hepatic function abnormal	1/1273 (0.1%)
Jaundice cholestatic	1/1273 (0.1%)
Infections and infestations
Pneumonia	12/1273 (0.9%)
Respiratory tract infection	3/1273 (0.2%)
Gastroenteritis	2/1273 (0.2%)
Bronchitis	1/1273 (0.1%)
Staphylococcal sepsis	1/1273 (0.1%)
Pneumonia bacterial	1/1273 (0.1%)
Lung infection	1/1273 (0.1%)
Infectious pleural effusion	1/1273 (0.1%)
Injury, poisoning and procedural complications
Fall	3/1273 (0.2%)
Femur fracture	2/1273 (0.2%)
Ankle fracture	1/1273 (0.1%)
Compression fracture	1/1273 (0.1%)
Shunt occlusion	1/1273 (0.1%)
Ulna fracture	1/1273 (0.1%)
Investigations
C-reactive protein increased	1/1273 (0.1%)
Metabolism and nutrition disorders
Hypoglycaemia	1/1273 (0.1%)
Hyperphosphatasaemia	1/1273 (0.1%)
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis	1/1273 (0.1%)
Trigger finger	1/1273 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	6/1273 (0.5%)
Lung adenocarcinoma	3/1273 (0.2%)
Prostate cancer	2/1273 (0.2%)
Colon cancer	1/1273 (0.1%)
Lung adenocarcinoma recurrent	1/1273 (0.1%)
Metastases to bone	1/1273 (0.1%)
Small cell lung cancer	1/1273 (0.1%)
Squamous cell carcinoma of lung	1/1273 (0.1%)
Lung neoplasm malignant	1/1273 (0.1%)
Hepatocellular carcinoma	1/1273 (0.1%)
Nervous system disorders
Cerebral infarction	2/1273 (0.2%)
Dementia	1/1273 (0.1%)
Seizure	1/1273 (0.1%)
Renal and urinary disorders
Dysuria	1/1273 (0.1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	12/1273 (0.9%)
Pneumothorax	7/1273 (0.5%)
Pneumonia aspiration	4/1273 (0.3%)
Interstitial lung disease	3/1273 (0.2%)
Hypoxia	2/1273 (0.2%)
Respiratory failure	2/1273 (0.2%)
Acute respiratory failure	1/1273 (0.1%)
Aspiration	1/1273 (0.1%)
Asthma	1/1273 (0.1%)
Epistaxis	1/1273 (0.1%)
Haemoptysis	1/1273 (0.1%)
Hypercapnia	1/1273 (0.1%)
Idiopathic pulmonary fibrosis	1/1273 (0.1%)
Pulmonary hypertension	1/1273 (0.1%)
Pneumomediastinum	1/1273 (0.1%)
Asthma-chronic obstructive pulmonary disease overlap syndrome	1/1273 (0.1%)
Vascular disorders
Aortic dissection	1/1273 (0.1%)
Other (Not Including Serious) Adverse Events
	Spiolto®
	Affected / at Risk (%)	# Events
Total	0/1273 (0%)

Limitations/Caveats

The study was conducted in an unblinded manner and without controls. The explanatory power of the study results was limited and the study results should be interpreted with the necessary caution.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.