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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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01978145
First received: October 31, 2013
Last updated: November 6, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: FSC
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised Multi-Centre, Double-Blind, Double-Dummy, Two Way Cross-Over, Twelve Weeks Non-inferiority Study to Evaluate The Efficacy, Safety, and Tolerability of Combination Dry Powder of Fluticasone Propionate and Salmeterol 250/50 mcg Twice Daily Delivered Through a Capsule-Based Inhaler and a Multi-Dose Inhaler for the Treatment of Chronic Obstructive Pulmonary Disease (COPD)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from Baseline in trough morning Forced expiratory volume in 1 second (FEV1) [ Time Frame: Day 85 of each Treatment Period ] [ Designated as safety issue: No ]
    Trough FEV1 will be measured electronically by a spirometer in the morning, before using the bronchodilator and predose


Secondary Outcome Measures:
  • Estimation of FEV1 area under the curve from 0 to 10 hours (AUC [0-10]) [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 2, 4, 6, and 10 hours post morning dose on Day 85 at the end of each Treatment Period ] [ Designated as safety issue: No ]
    The FEV1 (for determination of AUC 0 to10 hours) will be measured at clinic Visits 5 and Visit 9.

  • Measurement of severity of breathlessness using Transition Dyspnoea Index (TDI) [ Time Frame: Day 28, Day 56 and Day 85 of both Treatment Periods ] [ Designated as safety issue: No ]
    The TDI focal score is a sum of 3 components: functional impairment, magnitude of task, and magnitude of effort. A score of 1 or higher is considered to be a clinically meaningful change. It is interview-based measurement of breathlessness due to COPD, related to activities of daily living.

  • Change from Baseline in St George's Respiratory Questionnaire-COPD (SGRQ C) score [ Time Frame: Day 1 and Day 85 for each Treatment Period ] [ Designated as safety issue: No ]
    The SGRQ-C is a COPD-specific questionnaire that produces scores for symptoms, activity, and impact. The SGRQ-C is a 40-item COPD-specific questionnaire designed to measure the effect of COPD and its treatment on the subject's health-related QoL. The SGRQ-C ranges from 0 (no impairment of QoL) to 100 (highest impairment of QoL)

  • Change from Baseline in COPD Assessment Test (CAT) scores [ Time Frame: Day 1 and Day 85 for each Treatment Period ] [ Designated as safety issue: No ]
    The CAT is an 8-item questionnaire. There are 6 possible answers to each question, which are associated with a score of 0 to 5. The scores from each question are summed to give an overall score. It is a subject-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of individual subjects.


Estimated Enrollment: 432
Study Start Date: November 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen A
Placebo administered BID by multi-dose inhaler followed by FSC (250/50 mcg) administered BID by capsule-based inhaler.
Drug: FSC
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
Drug: Placebo
Subject will be administered placebo via dry powder inhalation device or multi-dose dry powder inhalation device BID for each treatment periods
Experimental: Regimen B
FSC (250/50 mcg) administered BID by multi-dose inhaler followed by placebo administered BID by capsule-based inhaler.
Drug: FSC
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
Drug: Placebo
Subject will be administered placebo via dry powder inhalation device or multi-dose dry powder inhalation device BID for each treatment periods

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • A respiratory diagnosis other than COPD (e.g., lung cancer, bronchiectasis, sarcoidosis, tuberculosis, lung fibrosis), including subjects with a diagnosis of alpha-1-antitrypsin deficiency. Allergic rhinitis is not exclusionary
  • 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
  • Medications Prior to Screening: Use of the following medications within the defined times prior to Visit 1 (Screening and Run-in Visit): Short-acting beta-agonists (e.g., albuterol; 6 hours), Ipratropium; 6 hours, Ipratropium/albuterol combination product; 6 hours, Oral beta-agonists; 48 hours, Salmeterol and formoterol; 48 hours, Indacaterol; 5 days, Theophylline preparations; 12 hours, Tiotropium; 14 days, Phosphodiesterase 4 (PDE4) inhibitors (e.g., roflumilast); 14 days, Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton); 48 hours, Long-acting beta -agonist/inhaled corticosteroid combination products (e.g., fluticasone/salmeterol or budesonide/formoterol); 30 days, Inhaled corticosteroids; 30 days, Oral or parenteral corticosteroids; 30 days, any investigational drug; 30 days or 5 half-lives, whichever is longer.
  • Any intellectual deficiency including illiteracy, history of substance abuse in the 2 years prior to Visit 1 (including drug and alcohol), or other conditions, which will limit the validity of informed consent to participate in the study
  • Subjects who have participated in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1 (Screening and Run-in Visit) or who will enter the acute phase of a pulmonary rehabilitation program during the study. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
  • Supplemental oxygen, with the following exceptions:

Use at high altitude (>5000 feet) provided subject does not require a flow rate of >2 L/minute Use for exertion provided subject does not require >2 hours per day of oxygen and does not require a flow rate of >2 L/minute Use for nocturnal therapy provided subject does not require a flow rate of >2 L/minute

  • Pregnant females as determined by urine test at Visit 1(Screening and Run-in Visit) or prior to dosing. A confirmatory serum pregnancy test is required if the urine test is questionable or positive
  • Lactating females
  • A known history of a positive hepatitis B surface antigen or a positive hepatitis C.
  • Unable to comply with study procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01978145

  Show 52 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01978145     History of Changes
Other Study ID Numbers: 115646
Study First Received: October 31, 2013
Last Updated: November 6, 2014
Health Authority: Australia: Therapeutic Goods Administration

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

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Respiratory Tract Diseases
Pathologic Processes
Fluticasone
Salmeterol
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Allergic Agents
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Dermatologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014