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 (telos)

• ClinicalTrials.gov Identifier: NCT02766608
• Recruitment Status: Completed
• First Posted: May 10, 2016
• Results First Posted: September 24, 2019
• Last Update Posted: September 24, 2019
• Sponsor: Pearl Therapeutics, Inc.
• Information provided by (Responsible Party): Pearl Therapeutics, Inc.

Tracking Information

• First Submitted Date: May 6, 2016
• First Posted Date: May 10, 2016
• Results First Submitted Date: November 30, 2018
• Results First Posted Date: September 24, 2019
• Last Update Posted Date: September 24, 2019
• Actual Study Start Date: May 31, 2016
• Actual Primary Completion Date: December 1, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 3, 2019)

• Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 (BFF MDI Versus FF MDI) [ Time Frame: 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) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: May 6, 2016)

• Change from baseline in morning pre-dose trough FEV1 [ Time Frame: at Week 24 ]
• Change from baseline in FEV1 AUC 0-4 [ Time Frame: at Week 24 ]

Current Secondary Outcome Measures (submitted: September 3, 2019)

• Time to First Moderate or Severe COPD Exacerbation (BFF MDI vs FF MDI). [ Time Frame: 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 [ Time Frame: 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.
• Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 (BFF MDI vs BD MDI) [ Time Frame: 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)
• Peak Change From Baseline in FEV1 at Week 24 (BFF MDI vs BD MDI) [ Time Frame: at Week 24 ]
  Peak change from baseline in FEV1 (Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI)
• Change From Baseline in Average Daily Rescue Ventolin HFA Use Over 24 Weeks (BFF MDI vs BD MDI) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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, 30 Minutes, Time to Onset of Action Determination [ Time Frame: 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.
• FEV1 on Day 1, 1 Hour, Time to Onset of Action Determination [ Time Frame: 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 [ Time Frame: 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.
• FEV1 on Day 1, 4 Hours, Time to Onset of Action Determination [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: May 6, 2016)

• Percentage of subjects achieving an MCID of 4 units or more in Saint George's [ Time Frame: at Week 24 ]
• Change from baseline in morning pre-dose trough FEV1 [ Time Frame: at Week 24 ]
• Peak change from baseline in FEV1 [ Time Frame: at Week 24 ]
• Change from baseline in average daily rescue Ventolin HFA use [ Time Frame: over 24 weeks ]
• Time to onset of action [ Time Frame: on Day 1 ]

Current Other Pre-specified Outcome Measures (submitted: September 3, 2019)

Substudy: 12-hour PFT Endpoint FEV1 AUC0-12 [ Time Frame: at Week 12 ]

Substudy: 12-hour PFT (Pulmonary Function Test) endpoint FEV1 (Forced Expiratory Volume) AUC0-12 (Area under the Curve 0-12). Changes from baseline in FEV1 AUC0-12 were normalized by taking the area under the curve value and dividing by the length of time under consideration. This normalization represents a weighted average of the change from baseline in FEV1 over the 12-hour period.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Randomized, Double-Blind, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT009 Compared to PT005, PT008, and Open-label Symbicort® Turbuhaler®, as an Active Control, on Lung Function Over a 24-Week Treatment Period in Subjects With Moderate to Very Severe COPD
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Obstructive Pulmonary Disorder

Intervention

• Drug: BFF MDI 320/9.6 μg
  Blinded Treatment
  Other Name: Budesonide and Formoterol Fumarate Inhalation Aerosol
• Drug: BFF MDI 160/9.6 μg
  Blinded Treatment
  Other Name: Budesonide and Formoterol Fumarate Inhalation Aerosol
• Drug: FF MDI 9.6 μg
  Blinded Treatment
  Other Name: Formoterol Fumarate Inhalation Aerosol
• Drug: BD MDI 320 μg
  Blinded Treatment
  Other Name: Budesonide Inhalation Aerosol
• Drug: Symbicort® TBH 400/12 μg BID
  Open Label
  Other Name: Symbicort® Turbuhaler

Study Arms

• Experimental: 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
  Intervention: Drug: BFF MDI 320/9.6 μg
• Experimental: 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
  Intervention: Drug: BFF MDI 160/9.6 μg
• Experimental: FF MDI 9.6 μg
  Formoterol Fumarate Inhalation Aerosol-4.8 μg per actuation MDI/ 120 inhalations Taken as 2 inhalations BID
  Intervention: Drug: FF MDI 9.6 μg
• Experimental: BD MDI 320 μg
  Budesonide inhalation Aerosol 160 μg per actuation MDI/120 inhalations Taken as 2 inhalations BID
  Intervention: Drug: BD MDI 320 μg
• Symbicort® TBH 400/12 μg
  Symbicort Turbuhaler 400/12 μg Taken as 2 inhalations BID
  Intervention: Drug: Symbicort® TBH 400/12 μg BID

Publications *

• Singh D, Hurst JR, Martinez FJ, Rabe KF, Bafadhel M, Jenkins M, Salazar D, Dorinsky P, Darken P. Predictive modeling of COPD exacerbation rates using baseline risk factors. Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221107314. doi: 10.1177/17534666221107314.
• Ferguson GT, Papi A, Anzueto A, Kerwin EM, Cappelletti C, Duncan EA, Nyberg J, Dorinsky P. Budesonide/formoterol MDI with co-suspension delivery technology in COPD: the TELOS study. Eur Respir J. 2018 Sep 16;52(3):1801334. doi: 10.1183/13993003.01334-2018. Print 2018 Sep.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 3, 2019): 2389
• Original Estimated Enrollment (submitted: May 6, 2016): 2420
• Actual Study Completion Date: December 1, 2017
• Actual Primary Completion Date: December 1, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Give their signed written informed consent to participate
2. Are at least 40 years of age and no older than 80 years
3. COPD patients who are symptomatic
4. Must be receiving one or more inhaled bronchodilators as maintenance therapy

Exclusion Criteria:

1. Current diagnosis of asthma,
2. COPD due to α1-Antitrypsin Deficiency
3. Known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis, Pulmonary resection or Lung Volume Reduction Surgery during the past 6 months
4. Long-term-oxygen therapy (≥ 12 hours a day).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czechia, Germany, Hungary, Korea, Republic of, Poland, Russian Federation, United States

Administrative Information

• NCT Number: NCT02766608
• Other Study ID Numbers: PT009002
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pearl Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Pearl Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Pearl Therapeutics, Inc.
• Verification Date: July 2019