Chronic Obstructive Pulmonary Disease MedDRA version: 17.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Fluticasone Propionate/Formoterol Fumarate Inhalation Suspension
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: Formoterol Fumerate
CAS Number: 43229-80-7
Other descripti
Sponsors
Mylan Pharma UK Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females at least 40 years of age. Females may be of either childbearing or non-childbearing potential. All females of childbearing potential must be using an acceptable, highly effect method of contraception and must also have a negative urine pregnancy test at screening. 2. A clinical diagnosis for at least 6 months prior to screening of COPD according to Global initiative for Obstructive Lung Disease guidelines (GOLD, 2014). 3. History of at least 10 pack-years of tobacco smoking. 4. Spirometry at Visit 1 and Visit 2 following 4 puffs (360 µg) albuterol pMDI via spacer showing: a) post-bronchodilator FEV1 =70% of predicted normal (Global Lung Function Initiative reference range; Quanjer et al, 2012) and, b) post-bronchodilator FEV1/FVC ratio =65 years) yes F.1.3.1 Number of subjects for this age range 583
Exclusion criteria
Exclusion criteria: 1.Current diagnosis of asthma 2.Alpha-1 anti-trypsin deficiency 3.Other chronic or active respiratory disorder 4.Symptoms of, or treatment for an AECOPD requiring antibiotics and/or oral/systemic corticosteroids or in-patient hospitalization during the 28 days preceding screening 5.Lower respiratory tract infection requiring treatment with antibiotics during the 28 days preceding screening 6.History or presence of pulmonary hypertension, respiratory failure, cor pulmonale or right ventricular failure 7.History of pulmonary lobectomy, lung volume reduction surgery, or lung transplantation 8.Use of supplemental oxygen therapy for more than 12 hours per day (includes night-time use) 9.Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the trial 10.Clinically significant, abnormal chest X-ray at screening indicating an active/significant disease process other than COPD. If a prior chest X-ray or thoracic high resolution CT scan within 6 months prior to screening is available this will be acceptable 11.History of long QT syndrome or screening ECG with QTcF greater than 460 milliseconds 12.History within past 5 years of paroxysmal atrial fibrillation.Patients with continuous atrial fibrillation controlled with a rate control strategy (i.e., cardioselective ß-blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) for at least 6 months may be included if the ventricular rate is below 100 bpm 13.Any other clinically significant abnormality on the 12-lead ECG at screening which in the judgment of the investigator would put the patient at potential risk if enrolled into the trial (these patients should not be re-screened) 14.Current evidence of, or history within the 6 months prior to screening of unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, or myocardial infarction 15.History of malignancy of any organ system treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases. The only exceptions are previous in situ carcinoma of the cervix, localized basal cell carcinoma of the skin or localized squamous carcinoma of the skin if the patient has been treated and is considered cured 16.Evidence of oropharyngeal candidiasis at screening 17.Known history of hypothalamic-pituitary-adrenal axis dysfunction 18.Uncontrolled glaucoma and/or raised IOP within 9 months of screening. Patients with chronic glaucoma will only be considered “controlled” and eligible for the trial if they have been on stable treatment (unchanged agent and dose) for the prior 9 months and they have had IOP measurement within this period documented as normal (=21 mm Hg; documented evidence will be required for eligibility) 19.Patients known to be HIV positive. Specific testing for HIV will not be conducted for this trial 20.Use of any investigational drug within 28 days, or 5 half lives, prior to screening whichever is longer 21.Use of medications with the potential to interact with fluticasone propionate, formoterol fumarate (as indicated in the current Investigators’ Brochure), albuterol or ipratropium bromide (as indicated in respective product labels), or medications with the potential to affect or confound COPD disease status 22.Patients with a history of reactions/hypersensitivity to any of the following inhaled drugs or drugs of a similar class: short- or long-acting
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy, as defined by FEV1 2-hours post-dose on Day 169, of FP/FF 500/10 fixed dose combination compared with FP inhalation suspension 500µg BID, in order to assess the contribution of the LABA component (FF) to the efficacy of the combination. To determine the efficacy, as defined by pre-dose FEV1 on Day 169, of FP/FF 500/10 and FP/FF 250/10 fixed dose combinations compared with FF inhalation solution 10µg BID, in order to assess the contribution of the ICS component (FP) to the efficacy of the combination.;Secondary Objective: - To assess the efficacy of FP/FF 500/10 and FP/FF 250/10 compared with placebo by evaluating quality of life (via SGRQ) and symptoms (via BDI/TDI), AECOPD and rescue medication use over 24 weeks. - To evaluate the long-term safety of treatment with the combination FP/FF inhalation suspension at doses of FP/FF 500/10 and FP/FF 250/10µg BID for up to 52 weeks.;Primary end point(s): 24 week placebo-controlled period Co-primary efficacy endpoints: - Change from baseline in pre-dose FEV1 at Day 169. - Change from baseline in 2-hour post-dose FEV1 at Day 169. 28-week extension period Primary endpoints – Safety - AEs/SAEs - Change from baseline in pre-dose vital signs (pulse rate, systolic and diastolic blood pressure) at Days 197, 281 and 365. - Change from baseline in pre-dose 12-lead ECG parameters at Days 197, 281 and 365. - Change from baseline in clinical chemistry and hematology parameters at Day 365. - Change from baseline in visual acuity, IOP and LOCS III lens grades to Day 365 (subset of patients).;Timepoint(s) of evaluation of this end point: 24 week placebo-controlled period - Both endpoints for will be assessed at Day 169. 28-week extension period - All but two endpoints will be assessed at Day 365 and some at Days 197 and 281. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 24 week placebo-controlled period Secondary Efficacy endpoints: • Rescue medication usage - Change from baseline in no. of puffs of albuterol during a 24-hour period (averaged over each successive 4 week treatment interval and over the entire 24-week period). - Change from baseline in percentage of rescue free 24-hour periods (during each successive 4 week treatment interval and over the entire 24-week treatment period). • Other spirometry - Change from baseline in pre-dose FEV1 on Days 15, 29, 57, 85 and 127. - Change from baseline in pre-dose FVC on Days 15, 29, 57, 85, 127 and 169. - Change from baseline in 2-hour post-dose FEV1 on Days 1 and 85. - Change from baseline in 2-hour post-dose FVC on Days 1, 85 and 169. - Onset of action (as measured by time to increase from pre-dose to post-dose FEV1 on Day 1 of = 100 mL or =12% on Day 1). - Peak FEV1 up to 2 hours post-dose on Day 1. - FEV1 AUC0-12 on Days 1 and 169 (subset of patients). - Trough FEV1 at 12 hours post-dose on Days 1 and 169 (subset of patients). • AECOPD - Proportion of patients with investigator-reported AECOPD (mild, moderate or severe, and moderate-or-severe) up to Day 169. - Time from Day 1 to first investigator-reported AECOPD (mild, moderate or severe, and moderate-or-severe). - Duration of investigator-reported AECOPD (mild, moderate or severe, and moderate-or-severe). - Proportion of patients with patient-reported AECOPD via EXACT-PRO up to Day 169. - Time from Day 1 to first patient-reported AECOPD via EXACT-PRO. - Duration of patient-reported AECOPD via EXACT-PRO. • Change from baseline in SGRQ total score and individual domain scores on Day 85 and Day 169. • TDI focal score on Days 15, 29, 57, 85, 127 and 169. Safety endpoints: • Adverse events (AEs)/serious AEs (SAEs). • Change from baseline in pre-dose vital signs (pulse rate, systolic and diastolic blood pressure) at Days 15, 29, 57, 85, 127 and 169. • Change from baseline in post-dose | — |
Countries
Argentina, Belgium, Canada, Chile, Colombia, Germany, Guatemala, Israel, Mexico, Netherlands, Peru, Poland, Russian Federation, Turkey, United States
Contacts
Public ContactRichard Allan
Mylan Pharma UK Ltd
Outcome results
None listed