A Non-inferiority Study to Evaluate the Efficacy, Safety, and Tolerability of Fluticasone Propionate/Salmeterol (FSC) 250/50 Microgram (mcg) Through a Capsule-Based Inhaler and a Multi-Dose Inhaler Administered Twice Daily (BID) in Adults With Chronic Obstructive Pulmonary Disease (COPD)

NCT01978145 | Completed Phase 3 Results

• 1 other identifier: 115646
• Study Type: interventional
• Target: 665
• Locations: 4 countries
• Sites: 52

Brief Summary

This is a multi-centre, randomised, double-blind, double-dummy, two way cross-over, 12 weeks noninferiority study to evaluate the efficacy, safety, and tolerability of FSC 250/50 mcg capsule-based inhaler and a multi-dose inhaler administered BID in adults with COPD. The primary objective of this study is to establish the non-inferiority of the efficacy of the FSC 250/50 mcg capsule-based inhaler compared to the FSC 250/50 mcg multi-dose inhaler administered BID. The study consists of 6 phases: Pre-screening, Screening/Run-in (3 weeks), Treatment Period 1 (12 weeks), Washout (minimum 4 weeks), Treatment Period 2 (12 weeks) and Follow-up (1 week). The total duration of the study for each subject will be at least 32 weeks.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

efficacy; tolerability; capsule-based inhaler; quality of life; safety; multi-dose inhaler; fluticasone propionate/salmeterol (FSC) 250/50 mcg; Chronic obstructive pulmonary disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Trough Morning Forced Expiratory Volume in 1 Second (FEV1) at Day 85

  Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. The trough FEV1 is defined as morning prebronchodilator and predose (12 hours after the last evening dose Day 84). Trough FEV1 was measured electronically by spirometer in the morning, before using the bronchodilator and predose, at Week 12 (Day 85) of each Treatment Period. Baseline was defined as the value obtained predose (0 minutes) on day 1 in each treatment period. Change from Baseline within each period was calculated as trough FEV1 at Day 85 minus the period specific Baseline value. The change from Baseline in trough FEV1 was analyzed using mixed model for repeated measures analysis, having fixed effect participant level Baseline, adjusted period-specific Baseline, treatment group, period, visit, visit by treatment, visit by participant level Baseline, visit by adjusted period-specific Baseline, with participant as random effect.

  Baseline and Day 85 of each treatment period

Secondary Outcomes (5)

• Change From Baseline in Trough Morning Forced Expiratory Volume in 1 Second (FEV1) at Day 28 and 56

  Baseline and Days 28 and 56 of each treatment period

• FEV1 Area Under the Curve From 0 to 10 Hours (AUC [0-10]) on Day 85 of Each Treatment Period

  Day 85 of each treatment period

• Change From Baseline in Transition Dyspnoea Index (TDI) Focal Score at Days 28, 56 and 85

  Baseline, and Days 28, 56 and 85

• Change From Baseline in St George's Respiratory Questionnaire-COPD (SGRQ C) Score at Week 12

  Baseline and Week 12 of each treatment period

• Change From Baseline in COPD Assessment Test (CAT) Scores at Week 12

  Baseline and Week 12 of each treatment period

Study Arms (2)

Regimen A

EXPERIMENTAL

Placebo administered BID by multi-dose inhaler followed by FSC (250/50 mcg) administered BID by capsule-based inhaler.

Drug: FSC; Drug: Placebo

Regimen B

EXPERIMENTAL

FSC (250/50 mcg) administered BID by multi-dose inhaler followed by placebo administered BID by capsule-based inhaler.

Drug: FSC; Drug: Placebo

Interventions

FSC DRUG

Subject will be administered FSC 250 mcg/50 mcg via dry powder inhalation device -or multi-dose dry powder inhalation device BID for each treatment periods

Regimen A; Regimen B

Placebo DRUG

Subject will be administered placebo via dry powder inhalation device or multi-dose dry powder inhalation device BID for each treatment periods

Regimen A; Regimen B

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 \>=40 and \<=80 years of age at the time of signing the informed consent.
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as premenopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \>40 milli international unit per milliliter (mIU/mL) and oestradiol \<40 picogram \[pg\]/mL \[\<147 picomole per liter (pmol/L)\] is confirmatory); females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods (i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study from Screening to follow-up contact) if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrolment. For most forms of HRT, at least 2 to 4 weeks should elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. After confirmation of their postmenopausal status, they can resume use of HRT during the study without use of a contraceptive method; child-bearing potential and is abstinent or agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) before the start of dosing to sufficiently minimise the risk of pregnancy at that point. Female subjects must agree to use contraception until at least 2 days post the last dose of study treatment; abstinence from penile-vaginal intercourse must be consistent with the preferred and usual lifestyle of the subject.
• COPD Diagnosis: An established clinical history of COPD in accordance with the following definition by the American Thoracic Society/European Respiratory Society.
• Severity of Disease:
• A measured pre- and post-salbutamol/albuterol FEV1/forced vital capacity (FVC) ratio of \<0.70 at Visit 1 (Screening and Run-in Visit) A measured pre-salbutamol/albuterol FEV1 \<50% of predicted normal values at Visit 1 (Screening and Run-in Visit).
• A measured post-salbutamol/albuterol FEV1 \>=30% of predicted normal values at Visit 1 (Screening and Run-in Visit). Predicted values will be calculated using the National Health and Nutrition Examination Survey (NHANES) III reference equations.
• Tobacco Use: Current or prior history of at least 10 pack-years of cigarette smoking (e.g., 20 cigarettes/day for 10 years). One pack-year is defined as 20 manufactured cigarettes (1 pack) smoked per day for 1 year. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1 (Screening and Run-in Visit). Former smokers are eligible to enter the study provided they have at least 10 pack-years smoking history. Subjects making a conscious decision to stop smoking at any time during the study and who refrain from smoking for \>4 weeks will be discontinued from the study. Additionally, subjects who start smoking during the study and smoke for at least 7 consecutive days will be discontinued from the study.
• Dyspnoea: A score of \>=2 on the Modified Medical Research Council Dyspnoea Scale (mMRC) at Visit 1 (Screening and Run-in Visit)
• Liver Safety Criteria: Alanine aminotransferase (ALT) \<=2 the upper limit of normal (ULN), alkaline phosphatase and bilirubin \<=1.5 ULN (isolated bilirubin \>1.5 ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%) at Visit 1 (Screening and Run-in Visit)
• Electrocardiogram (ECG) Safety Criteria: The subject must have no ECG abnormalities that would, in the opinion of investigator, compromise subject safety, or significantly affect subject's ability to complete the trial. As such the investigator will determine the clinical significance of any ECG abnormality and determine if a subject is precluded from entering the study. At Visit 1 (Screening and Run-in Visit), ECG safety criteria must be:
• QT interval corrected for heart rate (QTc) or QT interval corrected for heart rate according to Fridericia formula (QTcF) \<450 milliseconds (msec) or QTc \<480 msec for subjects with a bundle branch block. Investigators will be responsible for ensuring appropriate clinical interpretation of ECGs
• Able to use the inhaler devices adequately after training
• Capable of giving informed consent, which includes compliance with the study requirements and restrictions listed in the consent form.

You may not qualify if:

• A current diagnosis of asthma
• Any clinically significant and uncontrolled disease, including but not limited to the following: neurological, psychiatric, renal, immunological, endocrine/metabolic (including uncontrolled diabetes, hypokalaemia or thyroid disease), cardiovascular, neuromuscular, hepatic, gastric, or haematological abnormalities, or peripheral vascular disease. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk or would affect the efficacy analysis if the disease/condition exacerbated during the study
• An abnormal and clinically significant chest X-ray film or computed tomography scan not believed to be a result of the presence of COPD. A chest X-ray must be taken if the subject has not had 1 within 6 months of Visit 1 (Screening and Run in Visit)
• Lung resection surgery (e.g., lung volume reduction surgery, or lobectomy) within 1 year of Visit 1 (Screening and Run-in Visit)
• A COPD exacerbation and/or infection of the upper or lower respiratory tract requiring treatment with systemic (oral or parenteral) corticosteroids and/or antibiotics that has not resolved within 30 days of Visit 1 (Screening and Run-in Visit)
• A COPD exacerbation that resulted in hospitalisation that has not resolved within 3 months of Visit 1 (Screening and Run-in Visit)
• Use of nocturnal-positive pressure (e.g., continuous positive airway pressure or bilevel positive airway pressure)
• Oropharyngeal Examination: A subject will not be eligible for the Run-in Period if he/she has clinical visual evidence of candidiasis at Visit 1 (Screening and Run-in Visit)
• An abnormal and clinically significant 12-lead ECG result. For the purposes of this study, an abnormal ECG result is defined as a 12-lead tracing that is interpreted as demonstrating (but not limited to) any of the following: Myocardial ischemia, clinically significant conduction abnormalities (e.g., left bundle branch block, Wolff-Parkinson-White syndrome), clinically significant arrhythmias (e.g., atrial fibrillation, ventricular tachycardia). The study investigator will determine the clinical significance of any ECG abnormality and determine if a subject is precluded from entering the study.
• Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma, and basal cell carcinoma of the skin would not be excluded if the subject has been considered cured within 5 years since diagnosis
• Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Visit 1 (Screening and Run-in Visit) or within 5 half lives of the prior investigational drug (whichever is longer of the two). The prior investigational drug half life may be confirmed with the prior investigational study sponsor or by consulting relevant study documentation
• Allergies: Drug allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the capsule-based and multi-dose inhaler (i.e., lactose), milk protein allergy: History of severe milk protein allergy
• Initiation of systemic beta-blocker medications and beta-blocker eye drops for at least 30 days prior to Visit 1 (Screening and Run-in Visit)
• Concomitant Medication: Administration of prescription or over-the-counter medication that would significantly affect the course of COPD, or interact with study treatment, such as: anticonvulsants (barbiturates, hydantoins, carbamazepine); polycyclic antidepressants; phenothiazines; and monoamine oxidase (MAO) inhibitors; Immunosuppressive medications: A subject must not be using or require use of immunosuppressive medications during the study; cytochrome P450 3A4 (CYP3A4) inhibitors: Subjects who have received a potent CYP3A4 inhibitor within 4 weeks of Visit 1 (Screening and Run-in Visit) (e.g., ritonavir, ketoconazole, itraconazole) and at any time during the study; unable to refrain from the use of prescription or nonprescription drugs, including vitamins, herbal and dietary supplements (including St John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half lives (whichever is longer) prior to the first dose of study treatment, unless in the opinion of the investigator and medical monitor the medication will not interfere with the study procedures or compromise subject safety
• Compliance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, disease, or geographical location that seems likely (in the opinion of the investigator) to impair compliance with any aspect of this study protocol, including visit schedule and completion of the daily paper Diary Cards

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (52)

GSK Investigational Site

Mar del Plata, Buenos Aires, 7600, Argentina

Location

GSK Investigational Site

Quilmes, Buenos Aires, B1878FNR, Argentina

Location

GSK Investigational Site

San Juan Bautista, Buenos Aires, 1888, Argentina

Location

GSK Investigational Site

Bahía Blanca, 8000, Argentina

Location

GSK Investigational Site

Buenos Aires, 1407, Argentina

Location

GSK Investigational Site

Buenos Aires, C1180AAX, Argentina

Location

GSK Investigational Site

Buenos Aires, C1424BSF, Argentina

Location

GSK Investigational Site

Buenos Aires, C1425BEN, Argentina

Location

GSK Investigational Site

Florida, 1638, Argentina

Location

GSK Investigational Site

La Plata, 1900, Argentina

Location

GSK Investigational Site

Lanús, B1824DLR, Argentina

Location

GSK Investigational Site

Lanús, B1824KAJ, Argentina

Location

GSK Investigational Site

Mendoza, M5500CCG, Argentina

Location

GSK Investigational Site

Guadalajara, Jalisco, 44100, Mexico

Location

GSK Investigational Site

Guadalajara, Jalisco, 44280, Mexico

Location

GSK Investigational Site

Monterrey, Nuevo León, 64020, Mexico

Location

GSK Investigational Site

Monterrey, Nuevo León, 64460, Mexico

Location

GSK Investigational Site

Baja California, 22010, Mexico

Location

GSK Investigational Site

Chihuahua City, 31203, Mexico

Location

GSK Investigational Site

Durango, 34270, Mexico

Location

GSK Investigational Site

Hidalgo, 42090, Mexico

Location

GSK Investigational Site

Jalisco, 44130, Mexico

Location

GSK Investigational Site

Barnaul, 656045, Russia

Location

GSK Investigational Site

Nizhny Novgorod, 603011, Russia

Location

GSK Investigational Site

Novosibirsk, 630099, Russia

Location

GSK Investigational Site

Penza, 440026, Russia

Location

GSK Investigational Site

Perm, 614068, Russia

Location

GSK Investigational Site

Ryazan, 390026, Russia

Location

GSK Investigational Site

Ryazan, 390039, Russia

Location

GSK Investigational Site

Saint Petersburg, 192242, Russia

Location

GSK Investigational Site

Saint Petersburg, 194044, Russia

Location

GSK Investigational Site

Saint Petersburg, 195271, Russia

Location

GSK Investigational Site

Smolensk, 214006, Russia

Location

GSK Investigational Site

Tomsk, 634003, Russia

Location

GSK Investigational Site

Tomsk, 634050, Russia

Location

GSK Investigational Site

Yaroslavl, 150003, Russia

Location

GSK Investigational Site

Yekaterinburg, 620039, Russia

Location

GSK Investigational Site

Cherkasy, 18009, Ukraine

Location

GSK Investigational Site

Chernivtsi, 58005, Ukraine

Location

GSK Investigational Site

Dnipropetrovsk, 49005, Ukraine

Location

GSK Investigational Site

Ivano-Frankivsk, 76008, Ukraine

Location

GSK Investigational Site

Ivano-Frankivsk, 76018, Ukraine

Location

GSK Investigational Site

Kharkiv, 61039, Ukraine

Location

GSK Investigational Site

Kherson, 73000, Ukraine

Location

GSK Investigational Site

Kyiv, 1133, Ukraine

Location

GSK Investigational Site

Kyiv, 3680, Ukraine

Location

GSK Investigational Site

Odesa, 65025, Ukraine

Location

GSK Investigational Site

Poltava, 36010, Ukraine

Location

GSK Investigational Site

Sumy, 40000, Ukraine

Location

GSK Investigational Site

Vinnytsia, 21029, Ukraine

Location

GSK Investigational Site

Zaporizhzhia, 69035, Ukraine

Location

GSK Investigational Site

Zaporizhzhia, 69050, Ukraine

Location

Related Publications (1)

• Chan R, Sousa AR, Hynds P, Homayoun-Valiani F, Edwards D, Tabberer M. Assessment of the efficacy and safety of fluticasone propionate and salmeterol delivered as a combination dry powder via a capsule-based inhaler versus a multi-dose inhaler in patients with chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2017 Apr;43:12-19. doi: 10.1016/j.pupt.2017.01.009. Epub 2017 Jan 21.

  PMID: 28115223 DERIVED

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

Condition Hierarchy (Ancestors)

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

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 7, 2013
• Study Start: November 14, 2013
• Primary Completion: April 16, 2015
• Study Completion: April 16, 2015
• Last Updated: August 22, 2017
• Results First Posted: January 18, 2016

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

RU (15); AR (13); ME (9); UA (15)