A 3 Way Cross-over Study Evaluating the Effects of ADOAIR Twice Daily Plus Tiotropium Bromide Once Daily Compared With the Individual Treatments of Japanese Subjects

NCT01751113 | Completed Phase 4 Results

• 1 other identifier: 116572
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the effects on lung function of a combination of ADOAIR 50/250mcg twice daily plus tiotropium bromide 18mcg once daily compared with the individual treatments (tiotropium bromide 18mcg once daily alone and ADOAIR 50/250mcg twice daily alone) in Japanese subjects with COPD. The study will utilize a three-way cross-over design with a 2-week wash-out period between each 4-week consecutive treatment period. The aim is to support the rationale for "triple combination" therapy by demonstrating that treatment with both ADOAIR and tiotropium can potentially produce improved, clinically relevant effects compared with either treatment alone. This study will utilize a range of lung function measures in order to fully assess the benefits of triple therapy. The primary endpoint will be based on airways conductance measured using plethysmography (sGaw measured over 4hours post dose (AUC 0-4hr) on Day 28). Secondary endpoints will include lung function measures based on plethysmography and spirometry. The lung function measures will be supported by measurement of the use of relief salbutamol .

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve Calculated From 0 to 4 Hours (AUC[0-4hr]) Specific Conductance (sGaw) After the Morning Dose of Study Medication at Day 28 of Each Treatment Period

  sGaw is a measure of airways conductance and is intimately related to the diameter of the airways and consequently the level of bronchodilation. Plethysmography was performed to assess sGaw. The AUC was determined by using the trapezoidal rule and then dividing by the relevant time interval. A natural logarithmic transformation was applied and the data was analyzed by a mixed model including treatment, period and Baseline sGaw fitted as fixed effects and participants fitted as a random effect. Treatment ratios of all statistical comparisons were calculated by taking the anti-log of the difference between the Least Square (LS) means.

  Day 28 of each treatment period (up to 35 days)

Secondary Outcomes (10)

• AUC (0-4hr) Specific Airway Resistance (sRaw) After the Morning Dose of Each Study Medication at Day 28 of Each Treatment Period

  Day 28 of each treatment period (up to 35 days)

• Post-dose sGaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period

  Day 28 of each treatment period (up to 35 days)

• Post-dose sRaw at 30, 75, 120 and 240 Minutes Post Dose at Day 28 of Each Treatment Period

  Day 28 of each treatment period (up to 35 days)

• Trough Forced Expiratory Volume in One Second (FEV1), Forced Vital Capacity (FVC), Inspiratory Capacity (IC), RV, TLC, and TGV at Each Clinic Visit Prior to the Morning Dose and Before the Use of Rescue Medication at Day 28 of Each Treatment Period

  Day 28 of each treatment period (up to 35 days)

• Trough FEV1/FVC Ratio, at Each Clinic Visit Prior to the Morning Dose and Before the Use of Rescue Medication at Day 28 of Each Treatment Period

  Day 28 of each treatment period (up to 35 days)

Study Arms (3)

fluticasone propionate/salmeterol

ACTIVE COMPARATOR

250mcg fluticasone + 50 mcg salmeterol, twice daily 4 week treatment in each treatment sequence (crossover design)

Drug: fluticasone propionate/salmeterol

tiotropium bromide

ACTIVE COMPARATOR

18 mcg tiotropium bromide, once daily 4 week treatment in each treatment sequence (crossover design)

Drug: tiotropium bromide

fluticasone propionate/salmeterol plus tiotropium bromide

ACTIVE COMPARATOR

250mcg fluticasone + 50 mcg salmeterol, twice daily plus 18 mcg tiotropium bromide, once daily 4 week treatment in each treatment sequence (crossover design)

Drug: fluticasone propionate/salmeterol plus tiotropium bromide

Interventions

fluticasone propionate/salmeterol DRUG

250mcg fluticasone + 50 mcg salmeterol, twice daily 4 week treatment in each treatment sequence (crossover design)

Also known as: ADOAIR is a registered trade mark of the GlaxoSmithKlline group of companies.

fluticasone propionate/salmeterol

tiotropium bromide DRUG

18 mcg tiotropium bromide, once daily 4 week treatment in each treatment sequence (crossover design)

tiotropium bromide

fluticasone propionate/salmeterol plus tiotropium bromide DRUG

250mcg fluticasone + 50 mcg salmeterol, twice daily plus 18 mcg tiotropium bromide, once daily 4 week treatment in each treatment sequence (crossover design)

Also known as: ADOAIR is a registered trade mark of the GlaxoSmithKlline group of companies.

fluticasone propionate/salmeterol plus tiotropium bromide

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 40 - 80 years inclusive
• Has an established clinical history of COPD (defined as per the GOLD definition)
• A signed and dated written informed consent is obtained from the subject prior to study participation
• The subject has a post-bronchodilator FEV1 of \>=30% to =\<75% of predicted normal at Visit 1
• The subject has a post-bronchodilator FEV1/ FVC ratio \<70% at Visit 1
• The subject achieves a score of 1 on the Modified Medical Research Council (mMRC) Dyspnoea Scale at Visit 1
• The subject is a current or ex-smoker with a smoking history of \> 10 pack-years (10 pack years is defined as 20 cigarettes per day for 10 years, or 10 cigarettes (or equivalent if subject smoked cigars or a pipe) per day for 20 years). Ex-smokers are required to have stopped smoking for at least 6 months prior to visit 1. Ex-smokers who stopped smoking less than 6 months ago will be defined as current smokers.
• QTc \<450 msec at Visit 1; or for patients with Bundle Branch Block QTc should be \<480 msec.
• (QTc(F) \<450msec, or \<480 in subjects with right bundle branch block, should be confirmed by the mean of three readings or one reading)
• ALT \< 2xULN and bilirubin/ALP \< 1.5xULN (\>35% direct bilirubin)
• A female is eligible to enter this study if she is: i)of non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal), ii)of child-bearing potential, but has a negative urinary pregnancy test at screening and agrees to take contraceptive precautions (including abstinence) which are adequate to prevent pregnancy during the study or iii)not a nursing mother

You may not qualify if:

• Has had a COPD exacerbation within the 4 weeks prior to Visit 1
• Had any changes in COPD medication in the 4 weeks prior to Visit 1
• Has plan to change the dosage of Xanthines or to stop receiving it during the study
• Has a current medical diagnosis of asthma
• Has a medical diagnosis of narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction that in the opinion of the investigator should prevent them from entering the study Note: As with other anticholinergic drugs, subjects with narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction should only be entered into the study at the Investigator's discretion
• Has known respiratory disorders other than COPD (e.g. lung cancer, sarcoidosis, tuberculosis or lung fibrosis)
• Has undergone lung surgery e.g., lung transplant and/or lung volume reduction
• Is currently receiving pulmonary rehabilitation
• Had a chest X-ray indicating diagnosis other than COPD that might interfere with the study (chest X-ray to be taken at entry, if subject has not had one or CT image taken within 3 months of Visit 1)
• Requires regular (daily) or long term oxygen therapy (LTOT). (LTOT is defined as . 12 hours oxygen use per day)
• Requires regular treatment with oral, parenteral, or depot corticosteroids or has received 2 or more periods of oral corticosteroids for COPD exacerbation in the last 6 months
• Received oral, parenteral, or depot corticosteroids in the 4 weeks prior to Visit 1
• Received antibiotic therapy for either a lower respiratory tract infection or for COPD exacerbation within the 4 weeks prior to Visit 1
• Has been hospitalized for a COPD exacerbation in the last year
• Receiving non-selective β-blockers (except eye drops)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Hokkaido, 070-8644, Japan

Location

GSK Investigational Site

Ibaraki, 319-1113, Japan

Location

GSK Investigational Site

Osaka, 530-0001, Japan

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Fluticasone-Salmeterol Drug Combination; Tiotropium Bromide; Fluticasone; Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2012
• First Posted: December 17, 2012
• Study Start: February 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: March 8, 2017
• Results First Posted: September 8, 2014

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will share

Locations

JP (3)