in subjects with chronic obstructive pulmonary disease (COPD) MedDRA version: 18.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Conditions
Interventions
Product Name: Fluticasone Furoate/Umeclidinium/Vilanterol
Product Code: GW685698/GSK573719/GW642444
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: FLUTICASONE FUROATE
CAS N
Sponsors
GlaxoSmithKline, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed Consent: A signed and dated written informed consent prior to study participation. 2. Type of subject: Outpatient. 3. Age: Subjects 40 years of age or older at Screening (V1). 4. Gender: Male or female subjects. Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: a. Non-reproductive potential defined as: - Pre-menopausal females with one of the following: - Documented tubal ligation - Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion - Hysterectomy - Documented Bilateral Oophorectomy - Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. b. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (see Appendix 5) from 30 days prior to the first dose of study treatmentand until after the last dose of study treatmentand completion of the follow-up visit. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. 5. COPD Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]. 6. Smoking History: Current or former cigarette smokers with a history of cigarette smoking of ?10 pack-years at Screening (V1) [number of pack years = (number of cigarettes per day/20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Screening (V1). NOTES: - Pipe and/or cigar use cannot be used to calculate pack-year history. 7. Severity of COPD symptoms: A score of ?10 on the COPD Assessment Test (CAT) at Screening (V1). 8. Severity of COPD Disease: A post-albuterol/salbutamol FEV1/FVC ratio of <0.70 at Screening (V1). 9. Existing COPD maintenance treatment: Subject must be receiving daily maintenance treatment for their COPD for at least 3 months prior to Screening (V1). NOTES: - Subjects receiving only PRN COPD medications are not eligible. 10. History of Exacerbations: Subjects must demonstrate: a post-bronchodilator FEV1 < 50% predicted normal at Screening (V1) and a documented history of ? 1 moderate or severe COPD exacerbation in the 12 months prior to Screening OR a post-bronchodilator 50% ?FEV1 < 80% predicted normal at Screening (V1) and a documented history of ? 2 moderate exacerbations or a documented history of ?1 severe COPD exacerbation (hospitalised) in the 12 months prior to Screening (V1). NOTES: - Percent predicted will be calculated using the European Respiratory Society Global Lung Function Init
Exclusion criteria
Exclusion criteria: 1. Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study. 2. Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD, which is the primary cause of their respiratory symptoms). 3. alfa-1-antitrypsin deficiency: Subjects with alfa-1-antitrypsin deficiency as the underlying cause of COPD. 4. Other respiratory disorders: Subjects with active tuberculosis are excluded. Subjects with other respiratory disorders are excluded if these conditions are the primary cause of their respiratory symptoms. 5. Lung resection: Subjects with lung volume reduction surgery (including procedures such as endobronchial valves) within the 12 months prior to Screening (V1). 6. Risk Factors for Pneumonia: immune suppression (e.g. advanced HIV with high viral load and low CD4 count, Lupus on immunosuppressants that would increase risk of pneumonia) or other risk factors for pneumonia. 7. Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 14 days prior to Screening (V1) and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable). 8. Other Respiratory tract infections that have not resolved at least 7 days prior to Screening (V1). 9. Abnormal Chest x-ray: Chest x-ray reveals evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD, or another condition that would hinder the ability to detect an infiltrate on chest x-ray. 10. Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled. 11. Unstable liver disease: ALT >2xULN; and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 120 BPM; - sustained or nonsustained VT; - Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had been inserted) 14. Contraindications: A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator contraindicates study participation. 15. Cancer: Subjects with carcinoma that has not been in complete remission for at least 3 years. Subjects who have had carcinoma in situ of the cervix, squamous cell carci
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effect of FF/UMEC/VI with FF/VI + UMEC on lung function after 24 weeks of treatment;Secondary Objective: - To compare the effects of FF/UMEC/VI with FF/VI + UMEC on health related quality of life and dyspnoea after 24 weeks of treatment. - To compare the effect of FF/UMEC/VI with FF/VI + UMEC on time to first moderate or severe exacerbation during 24 weeks of treatment. - To compare the PK of FF, UMEC and VI when given as FF/UMEC/VI or FF/VI+UMEC in a subset of subjects. - To compare the safety profile of FF/UMEC/VI with FF/VI + UMEC over 24 weeks of treatment.;Primary end point(s): Change from baseline in trough FEV1 at 24 weeks.;Timepoint(s) of evaluation of this end point: Spirometry will be done at visits 2,3,4 and 5. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of Responders based on the St George Respiratory Questionnaire (SGRQ) Total Score at Week 24 - Change from baseline in SGRQ Total Score at Week 24 - Proportion of Responders based on Transitional Dyspnoea Index (TDI) focal score at Week 24 - TDI focal score at Week 24 - Time to first moderate or severe exacerbation - Population PK (in a subset of approximately 180 subjects) - Incidence of adverse events and adverse events of special interest, - ECG measurements - Vital signs - Haematological and clinical chemistry parameters;Timepoint(s) of evaluation of this end point: Over 24 weeks For PK Subgroup A: At week 12 & Week 24 For PK Subgroup B: over 24 hrs starting at Week 12 For PK Sub-study: At Baseline, Week 12 and Week 24 | — |
Countries
Argentina, Australia, France, Germany, Italy, Japan, Korea, Republic of, Mexico, Poland, Romania, Russian Federation, Spain
Contacts
Public ContactCentro de Información
GlaxoSmithKline
Outcome results
None listed