Study to Assess Efficacy and Safety of PT009 Compared to PT005, PT008, and Symbicort® Turbuhaler® on Lung Function Over 24-Weeks in Subjects With Moderate to Very Severe COPD
- Conditions
- Chronic Obstructive Pulmonary Disorder
- Interventions
- Drug: FF MDI 9.6 μgDrug: BFF MDI 320/9.6 μgDrug: BFF MDI 160/9.6 μg
- Registration Number
- NCT02766608
- Lead Sponsor
- Pearl Therapeutics, Inc.
- Brief Summary
This is a Phase III randomized, double-blind, parallel group, multi-center, 24-week lung function study with BFF MDI (320/9.6 μg and 160/9.6 μg) compared to FF MDI 9.6 μg, BD MDI 320 μg, and open-label Symbicort® TBH (200/6 μg) administered BID.
- Detailed Description
This is a Phase III randomized, double-blind, parallel group, multi-center, 24-week lung function study with BFF MDI (320/9.6 μg and 160/9.6 μg) compared to FF MDI 9.6 μg, BD MDI 320 μg, and open-label Symbicort® TBH (200/6 μg) administered BID. Subjects will undergo a 1- to 4-week Screening Period. Subjects who successfully complete the Screening Period will be to one of the following five treatment groups:BFF MDI 320/9.6 μg BID (N=660), BFF MDI 160/9.6 μg BID, FF MDI 9.6 μg BID, BD MDI 320 μg BID, Symbicort®, TBH 400/12 μg BID. Following randomization, subjects will enter the Treatment Period and undergo additional treatment visits over 24 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2389
- Give their signed written informed consent to participate
- Are at least 40 years of age and no older than 80 years
- COPD patients who are symptomatic
- Must be receiving one or more inhaled bronchodilators as maintenance therapy
- Current diagnosis of asthma,
- COPD due to α1-Antitrypsin Deficiency
- Known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis, Pulmonary resection or Lung Volume Reduction Surgery during the past 6 months
- Long-term-oxygen therapy (≥ 12 hours a day).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BD MDI 320 μg BD MDI 320 μg Budesonide inhalation Aerosol 160 μg per actuation MDI/120 inhalations Taken as 2 inhalations BID FF MDI 9.6 μg FF MDI 9.6 μg Formoterol Fumarate Inhalation Aerosol-4.8 μg per actuation MDI/ 120 inhalations Taken as 2 inhalations BID BFF MDI 320/9.6 μg BFF MDI 320/9.6 μg Budesonide and Formoterol Fumarate Inhalation Aerosol 160/4.8 μg per actuation MDI/120 inhalations Taken as 2 inhalations BID BFF MDI 160/9.6 μg BFF MDI 160/9.6 μg Budesonide and Formoterol Fumarate Inhalation Aerosol-80/4.8 μg per actuation MDI/120 inhalations Taken as 2 inhalations BID Symbicort® TBH 400/12 μg Symbicort® TBH 400/12 μg BID Symbicort Turbuhaler 400/12 μg Taken as 2 inhalations BID
- Primary Outcome Measures
Name Time Method Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 (BFF MDI Versus FF MDI) at Week 24 Change from baseline in morning pre-dose trough FEV1 (Forced expiratory volume in 1 second) at Week 24 (BFF MDI versus FF MDI)
Change From Baseline in FEV1 AUC0-4 (BFF MDI vs BD MDI) at Week 24 Changes from baseline in FEV1 AUC0-4 were normalized by taking the area under the curve value and dividing by the length of time under consideration (usually 4 hours). This normalization represents a weighted average of the change from baseline in FEV1 over the 4-hour period.
- Secondary Outcome Measures
Name Time Method FEV1 on Day 1, 30 Minutes, Time to Onset of Action Determination Day 1 - 30 Minutes Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment.
Change From Baseline in Average Daily Rescue Ventolin HFA Use Over 24 Weeks (BFF MDI vs BD MDI) over 24 Weeks Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (BFF MDI vs BD MDI)
FEV1 on Day 1, 5 Minutes, Time to Onset of Action Determination Day 1 - 5 Minutes Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment.
FEV1 on Day 1, 15 Minutes, Time to Onset of Action Determination Day 1 - 15 Minutes Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment.
FEV1 on Day 1, 4 Hours, Time to Onset of Action Determination Day 1 - 4 Hours Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment.
Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 (BFF MDI vs BD MDI) at Week 24 Change from baseline in morning pre-dose trough FEV1(Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI)
FEV1 on Day 1, 1 Hour, Time to Onset of Action Determination Day 1 - 1 Hour Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment.
FEV1 on Day 1, 2 Hours, Time to Onset of Action Determination Day 1 - 2 Hours Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment.
Time to First Moderate or Severe COPD Exacerbation (BFF MDI vs FF MDI). over 24 Weeks (timepoints of 4, 12 & 20 weeks) Time to first moderate or severe COPD (Chronic Obstructive Pulmonary Disease) exacerbation (BFF MDI vs FF MDI).
Percentage of Subjects Achieving an MCID (Minimal Clinically Important Difference) of 4 Units or More in SGRQ at Week 24 at Week 24 The SGRQ (St. George's Respiratory Questionnaire) is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of BFF MDI, FF MDI, BD MDI, \& Symbicort TBH on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life.
Peak Change From Baseline in FEV1 at Week 24 (BFF MDI vs BD MDI) at Week 24 Peak change from baseline in FEV1 (Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI)
Trial Locations
- Locations (1)
Research Site
🇷🇺Yekaterinburg, Russian Federation