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

Chronic Obstructive Pulmonary Disorder Clinical Trial

— telos  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02766608
• Other study ID #: PT009002
• Status: Completed
• Phase: Phase 3
• Start date: May 31, 2016
• Est. completion date: December 1, 2017

Study information

• Verified date: July 2019
• Source: Pearl Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 2389
• Est. completion date: December 1, 2017
• Est. primary completion date: December 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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 a1-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).

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disorder
• Lung Diseases

Intervention

Drug:
• BFF MDI 320/9.6 µg
Blinded Treatment
• BFF MDI 160/9.6 µg
Blinded Treatment
• FF MDI 9.6 µg
Blinded Treatment
• BD MDI 320 µg
Blinded Treatment
• Symbicort® TBH 400/12 µg BID
Open Label

Locations

Country	Name	City	State
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Mirabel	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Pointe-Claire	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	St Charles Borromee	Quebec
Canada	Research Site	Sudbury	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Trois-Rivières	Quebec
Canada	Research Site	Truro	Nova Scotia
Canada	Research Site	Victoriaville	Quebec
Canada	Research Site	Windsor	Ontario
Canada	Research Site	Windsor	Ontario
Canada	Research Site	Winnipeg	Manitoba
Czechia	Research Site	Boskovice
Czechia	Research Site	Brandys nad Labem
Czechia	Research Site	Jindrichuv Hradec
Czechia	Research Site	Liberec
Czechia	Research Site	Lovosice
Czechia	Research Site	Novy Bor
Czechia	Research Site	Ostrava-Hrabuvka
Czechia	Research Site	Ostrava-Poruba
Czechia	Research Site	Prague
Czechia	Research Site	Praha
Czechia	Research Site	Praha
Czechia	Research Site	Praha 6
Czechia	Research Site	Praha 9
Czechia	Research Site	Rokycany
Czechia	Research Site	Strakonice
Czechia	Research Site	Teplice
Czechia	Research Site	Varnsdorf
Czechia	Research Site	Zatec
Germany	Research Site	Bamberg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Darmstadt
Germany	Research Site	Essen
Germany	Research Site	Frankfurt
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Köln
Germany	Research Site	Leipzig
Germany	Research Site	Leipzig
Germany	Research Site	Lübeck
Germany	Research Site	Rodgau-Dudenhofen
Germany	Research Site	Schwerin
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Cegléd
Hungary	Research Site	Csorna
Hungary	Research Site	Gödöllo
Hungary	Research Site	Hajdúnánás
Hungary	Research Site	Hatvan
Hungary	Research Site	Komárom
Hungary	Research Site	Makó
Hungary	Research Site	Miskolc
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Pécs
Hungary	Research Site	Pécs
Hungary	Research Site	Siófok
Hungary	Research Site	Százhalombatta
Hungary	Research Site	Szeged
Hungary	Research Site	Szolnok
Korea, Republic of	Research Site	Anyang-si
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Jeonju-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Bielsko-Biala
Poland	Research Site	Chelm
Poland	Research Site	Elblag
Poland	Research Site	Gdansk
Poland	Research Site	Grudziadz
Poland	Research Site	Katowice
Poland	Research Site	Koscian
Poland	Research Site	Kraków
Poland	Research Site	Kraków
Poland	Research Site	Legnica
Poland	Research Site	Lódz
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Nowy Duninow
Poland	Research Site	Ostrów Wielkopolski
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Piekary Slaskie
Poland	Research Site	Pila
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Proszowice
Poland	Research Site	Pulawy
Poland	Research Site	Ruda Slaska
Poland	Research Site	Rzeszów
Poland	Research Site	Rzeszów
Poland	Research Site	Siedlce
Poland	Research Site	Sochaczew
Poland	Research Site	Suwalki
Poland	Research Site	Szczecin
Poland	Research Site	Tarnów
Poland	Research Site	Trzebnica
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wielun
Poland	Research Site	Wolomin
Poland	Research Site	Wroclaw
Poland	Research Site	Zabrze
Poland	Research Site	Zamosc
Russian Federation	Research Site	Barnaul
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ivanovo
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Kirov
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhny Novgorod
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Pytigorsk
Russian Federation	Research Site	Rostov-na-Donu
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	Smolensk
Russian Federation	Research Site	Smolensk
Russian Federation	Research Site	St-Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Ulyanovsk
Russian Federation	Research Site	Vladimir
Russian Federation	Research Site	Voronezh
Russian Federation	Research Site	Yaroslavl
Russian Federation	Research Site	Yaroslavl
Russian Federation	Research Site	Yekaterinburg
Russian Federation	Research Site	Yekaterinburg
United States	Research Site	Anaheim	California
United States	Research Site	Anderson	South Carolina
United States	Research Site	Athens	Alabama
United States	Research Site	Bellevue	Washington
United States	Research Site	Bellevue	Washington
United States	Research Site	Birmingham	Alabama
United States	Research Site	Blue Ridge	Georgia
United States	Research Site	Boulder	Colorado
United States	Research Site	Channelview	Texas
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Clearwater	Florida
United States	Research Site	Clearwater	Florida
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Columbus	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Dayton	Ohio
United States	Research Site	DeLand	Florida
United States	Research Site	Dothan	Alabama
United States	Research Site	Dublin	Ohio
United States	Research Site	Easley	South Carolina
United States	Research Site	Edina	Minnesota
United States	Research Site	Fargo	North Dakota
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Fridley	Minnesota
United States	Research Site	Gaffney	South Carolina
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Gold River	California
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Grove City	Ohio
United States	Research Site	Hamden	Connecticut
United States	Research Site	Henderson	Nevada
United States	Research Site	Henderson	Nevada
United States	Research Site	Hialeah	Florida
United States	Research Site	Huntersville	North Carolina
United States	Research Site	Indian Land	South Carolina
United States	Research Site	Jackson Heights	New York
United States	Research Site	Johnson City	Tennessee
United States	Research Site	Kingsport	Tennessee
United States	Research Site	Larchmont	New York
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Littleton	Colorado
United States	Research Site	Live Oak	Texas
United States	Research Site	Medford	Oregon
United States	Research Site	Meridian	Idaho
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Mount Pleasant	South Carolina
United States	Research Site	New Braunfels	Texas
United States	Research Site	Newport News	Virginia
United States	Research Site	North Dartmouth	Massachusetts
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Palm Springs	California
United States	Research Site	Panama City	Florida
United States	Research Site	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Port Orange	Florida
United States	Research Site	Port Orange	Florida
United States	Research Site	Richmond	Virginia
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Sacramento	California
United States	Research Site	Saint Charles	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Seneca	South Carolina
United States	Research Site	South Burlington	Vermont
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Sugar Land	Texas
United States	Research Site	Tacoma	Washington
United States	Research Site	Tampa	Florida
United States	Research Site	Towson	Maryland
United States	Research Site	Tucson	Arizona
United States	Research Site	Union	South Carolina
United States	Research Site	Westminster	Maryland
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winter Park	Florida
United States	Research Site	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Pearl Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Hungary,  Korea, Republic of,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Substudy: 12-hour PFT Endpoint FEV1 AUC0-12	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.	at Week 12
Primary	Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 (BFF MDI Versus FF MDI)	Change from baseline in morning pre-dose trough FEV1 (Forced expiratory volume in 1 second) at Week 24 (BFF MDI versus FF MDI)	at Week 24
Primary	Change From Baseline in FEV1 AUC0-4 (BFF MDI vs BD MDI)	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.	at Week 24
Secondary	Time to First Moderate or Severe COPD Exacerbation (BFF MDI vs FF MDI).	Time to first moderate or severe COPD (Chronic Obstructive Pulmonary Disease) exacerbation (BFF MDI vs FF MDI).	over 24 Weeks (timepoints of 4, 12 & 20 weeks)
Secondary	Percentage of Subjects Achieving an MCID (Minimal Clinically Important Difference) of 4 Units or More in SGRQ 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.	at Week 24
Secondary	Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 (BFF MDI vs BD MDI)	Change from baseline in morning pre-dose trough FEV1(Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI)	at Week 24
Secondary	Peak Change From Baseline in FEV1 at Week 24 (BFF MDI vs BD MDI)	Peak change from baseline in FEV1 (Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI)	at Week 24
Secondary	Change From Baseline in Average Daily Rescue Ventolin HFA Use Over 24 Weeks (BFF MDI vs BD MDI)	Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (BFF MDI vs BD MDI)	over 24 Weeks
Secondary	FEV1 on Day 1, 5 Minutes, Time to Onset of Action Determination	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.	Day 1 - 5 Minutes
Secondary	FEV1 on Day 1, 15 Minutes, Time to Onset of Action Determination	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.	Day 1 - 15 Minutes
Secondary	FEV1 on Day 1, 30 Minutes, Time to Onset of Action Determination	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.	Day 1 - 30 Minutes
Secondary	FEV1 on Day 1, 1 Hour, Time to Onset of Action Determination	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.	Day 1 - 1 Hour
Secondary	FEV1 on Day 1, 2 Hours, Time to Onset of Action Determination	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.	Day 1 - 2 Hours
Secondary	FEV1 on Day 1, 4 Hours, Time to Onset of Action Determination	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.	Day 1 - 4 Hours

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