Tiotropium/Salmeterol/Fluticasone Fixed Dose Combination Tratment Via Discair vs Tiotropium Via Handihaler + Salmeterol/Fluticasone Via Diskus Free Combination Treatment

Comparison of Bronchodilator Efficacy of Tiotropium/Salmeterol/Fluticasone 9/50/500 mcg Combination Treatment Administered Via Discair® With Original Products Seretide Diskus 500 mcg Inhalation Powder Plus Spiriva 18 mcg Inhalation Powder Treatment in Patients With Moderate-severe Chronic Obstructive Pulmonary Disease (COPD)

The overall objective is to asses the bronchodilator effect of Tiotropium/Salmeterol/Fluticasone combination delivered via Discair® twice daily as compared with original products Seretide Diskus 500 mcg Inhalation Powder twice daily and Spiriva 18 mcg Inhalation Powder once daily free combination treatment in patients with stable moderate to severe COPD.

Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Tiotropium/Salmeterol/Fluticasone 9/50/500 mcg Inhalation Powder; Drug: Tiotropium 18 mcg Inhalation Powder; Drug: Salmeterol/Fluticasone 50/500 mcg Inhalation Powder

Detailed Description

The overall objective is to asses the bronchodilator effect of Tiotropium/Salmeterol/Fluticasone combination delivered via Discair® twice daily as compared with original products Seretide Diskus 500 mcg Inhalation Powder twice daily and Spiriva 18 mcg Inhalation Powder once daily free combination treatment in patients with stable moderate to severe COPD.

For formerly diagnosed patients who met all the inclusion criteria and receiving COPD treatment, the day of the screening visit will be based on the completion of a run-in period, with the length determined by the specific medication. During the run-in period, salbutamol (100 μg inhaler) will be prescribed as a rescue medication.

Patients (following run-in period for formerly diagnosed patients) will be randomly assigned to receive Tiotropium/Salmeterol/Fluticasone fixed dose combination as dry powder inhalation delivered via Discair® twice daily or Seretide Diskus 500 mcg Inhalation Powder twice daily and Spiriva 18 mcg Inhalation Powder once daily free combination for 2-days treatment period.

Patients will be evaluated at 4 consecutive visits: baseline (enrollment), screening, treatment and after treatment.

Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey
  • Adana, Turkey
    • Cukurova University Faculty of Medicine, Chest Diseases Department
  • Istanbul, Turkey
    • Health Sciences University, Sureyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged ≥40 years with COPD diagnosis according to the GOLD (The Global Initiative for Chronic Obstructive Lung Disease) strategy.
• Patients who have symptomatic stable moderate to severe COPD diagnosis with post-bronchodilator FEV1/FVC ratio <0.70, and FEV1 <80% of predicted normal value at screening visit.
• Patients with a mMRC score ≥2
• Current smokers or ex-smokers with a smoking history of at least 10 pack-years
• Patients who have an exacerbation within least a year and no exacerbation within last 4 weeks
• Females patients with childbearing potential using effective birth control method
• Patients who has a capability of communicate with investigator
• Patients who accept to comply with the requirements of the protocol
• Patients who signed written informed consent prior to participation

Exclusion Criteria:

• History of hypersensitivity to drugs contains long acting beta-2 agonists, corticosteroids, anticholinergics or lactose.
• History of asthma or significant chronic respiratory diseases except COPD.
• Patients who had COPD exacerbation or lower respiratory track infections that required antibiotic, oral or parenteral corticosteroid treatment within 4 weeks prior to screening visit or during run-in period.
• Patients with serum potassium level ≤ 3.5 mEq/L or >5.5 mEq/L
• Patients who used systemic corticosteroids or immunosupresants within 4 weeks prior to study onset
• Patients who have a history of myocardial infarction, hearth failure, acute ischemic coroner disease or severe cardiac arrhythmia requiring treatment within least 6 weeks
• Patients who have lung cancer
• Patients who had lung volume reduction operation
• Patients who had live attenuated vaccines within 2 weeks prior to screening visit or during run-in period
• Women patients who are pregnant or nursing
• History of allergic rhinitis or atopy
• Known symptomatic prostatic hypertrophy requiring drug therapy or operation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tiotropium/Salmeterol/Fluticasone; Tiotropium/Salmeterol/Fluticasone 9/50/500 mcg Inhalation Powder (1 puff) twice daily (approximately every 12 hr) via Discair®	Drug: Tiotropium/Salmeterol/Fluticasone 9/50/500 mcg Inhalation Powder; Tiotropium/Salmeterol/Fluticasone 9/50/500 mcg Inhalation Powder (1 puff) twice daily via Discair® for two days.; Other Names: Saltif 9/50/500 mcg Inhalation Powder
Active Comparator: Tiotropium + Salmeterol/Fluticasone; Tiotropium 18 mcg Inhalation Powder (1 puff) once daily via Handihaler® + Salmeterol/Fluticasone 50/500 mcg Inhalation Powder (1 puff) twice daily (approximately every 12 hr) via Diskus®	Drug: Tiotropium 18 mcg Inhalation Powder; Tiotropium 18 mcg Inhalation Powder (1 puff) once daily via Handihaler® for two days.; Other Names: Spiriva 18 mcg Inhalation Powder; Drug: Salmeterol/Fluticasone 50/500 mcg Inhalation Powder; Salmeterol/Fluticasone 50/500 mcg Inhalation Powder (1 puff) twice daily (approximately every 12 hr) via Diskus® for two days; Other Names: Seretide Diskus® 500 mcg Inhalation Powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean max change (ml) from baseline in FEV1 over a period of 48 hrs.	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	48 hrs
Mean % change from baseline in FEV1 over a period of 48 hrs.	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	48 hrs
Mean max change (ml) from baseline in FVC over a period of 48 hrs.	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	48 hrs
Mean % change from baseline in FVC over a period of 48 hrs.	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	48 hrs
FEV1 (AUC0-12) response [AUC: area under the curve; response defined as change from baseline]	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	Day 1: 0-12 hrs
FVC (AUC0-12) response	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	Day 1: 0-12 hrs
FEV1 (AUC12-24) response	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	Day 1: 12-24 hrs
FVC (AUC12-24) response	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	Day 1: 12-24 hrs
FEV1 (AUC24-48) response	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	Day 2: 0-24 hrs
FVC (AUC24-48) response	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	Day 2: 0-24 hrs
FEV1 (AUC0-48) response	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	48 hrs
FVC (AUC0-48) response	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	48 hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time to onset of bronchodilator effect	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	48 hrs
The time to onset of maximum effect	Spirometric measurements will be performed totally at 15 different time points at pretreatment and post-treatment (pre-dose, 15. min, 30. min, 1. hr, 2. hr, 4.hr, 8.hr and 12.hr) during the first treatment day and at 16 different time points (15. min, 30. min, 1. hr, 2. hr, 4.hr, 6 hr, 8.hr and 12.hr) during the second treatment day.	48 hrs
Evaluation of safety of study drug	Number of participants with treatment-related adverse events and/or abnormal laboratory values.	48 hrs

Collaborators and Investigators

• Sponsor: Neutec Ar-Ge San ve Tic A.Ş

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2018
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: December 7, 2017
• First Submitted That Met QC Criteria: January 3, 2018
• First Posted (Actual): January 9, 2018

Study Record Updates

• Last Update Posted (Actual): June 12, 2020
• Last Update Submitted That Met QC Criteria: June 11, 2020
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: COPD; Spirometry; Tiotropium; Fluticasone; Salmeterol; Diskus; Discair; Bronchodilator effect
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Fluticasone; Xhance; Salmeterol Xinafoate; Tiotropium Bromide
• Other Study ID Numbers: NEU-01.17

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No