Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD); (PINNACLE 1)

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

A Randomized, Double Blind, Chronic Dosing, Placebo-Controlled, Parallel Group, Multi Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD, Compared With Placebo and Spiriva® Handihaler® (Tiotropium Bromide 18 µg Open-Label) as an Active Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01854645
• Other study ID #: PT003006-00
• Status: Completed
• Phase: Phase 3
• First received: May 13, 2013
• Last updated: July 7, 2015
• Start date: May 2013
• Est. completion date: February 2015

Study information

• Verified date: July 2015
• Source: Pearl Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The overall objective of this study is to assess the efficacy and safety of treatment with PT003 (GFF MDI), PT005 (FF MDI), PT001 (GP MDI), and open-label tiotropium bromide inhalation powder compared with each other and Placebo MDI over 24 weeks in subjects with moderate to very severe COPD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2103
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

Key Inclusion Criteria:

• Male or female subjects at least 40 years of age and no older than 80 at Visit 1.

• Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)

• Current or former smokers with a history of at least 10 pack-years of cigarette smoking.

• Average f the -60 and the -30 min pre-dose FEV1 assessments must be < 80% predicted normal value calculated using National Health and Nutrition Examination Survey (NHANES) III reference equations.

• Subjects willing and, in the opinion of the investigator, able to adjust current COPD therapy as required by the protocol

Key Exclusion Criteria:

• Significant diseases other than COPD, i.e. disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study

• Current diagnosis of asthma or alpha-1 antitrypsin deficiency

• Other active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or uncontrolled sleep apnea

• Hospitalized due to poorly controlled COPD within 3 months prior to screening or during the Screening Period

• Poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to screening or during the Screening Period

• Lower respiratory tract infections that required antibiotics within 6 weeks prior to screening or during the Screening Period

• Unstable ischemic heart disease, left ventricular failure, or documented myocardial infarction within 12 months of enrollment.

• Recent history of acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass graft within the past three months

• Congestive heart failure (CHF) New York Heart Association (NYHA) Class III/IV)

• Clinically significant abnormal 12-lead ECG

• Abnormal liver function tests defined as aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin = 1.5 times upper limit of normal at Visit 1 and on repeat testing

• Cancer not in complete remission for at least five years

• History of hypersensitivity to ß2-agonists, glycopyrronium or other muscarinic anticholinergics, lactose/milk protein or any component of the MDI

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• GFF MDI
GFF MDI administered as two puffs BID
• GP MDI
GP MDI administered as two puffs BID
• FF MDI
FF MDI administered as two puffs BID
• Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®)
Taken as 1 capsule daily containing 18 µg of open-label tiotropium via the Handihaler dry powder inhaler (DPI)
• Placebo MDI
Inhaled placebo administered as two puffs BID

Locations

Country	Name	City	State
Australia	Pearl Investigative Site	Adelaide	South Australia
Australia	Pearl Investigative Site	Box Hill	Victoria
Australia	Pearl Investigative Site	Brisbane	Queensland
Australia	Pearl Investigative Site	Cairns	Queensland
Australia	Pearl Investigative Site	Daw Park	South Australia
Australia	Pearl Investigative Site	Heidelberg	Victoria
Australia	Pearl Investigative Site	Nedlands	Western Australia
Australia	Pearl Investigative Site	New Lambton	New South Wales
Australia	Pearl Investigative Site	Perth	Western Australia
Australia	Pearl Investigative Site	Toorak Gardens	South Australia
Australia	Pearl Investigative Site	Westmead	New South Wales
Australia	Pearl Investigative Site	Wooloongabba	Queensland
New Zealand	Pearl Investigative Site	Caversham	Dunedin
New Zealand	Pearl Investigative Site	Greenlane	East Aukland
New Zealand	Pearl Investigative Site	Hamilton	Waikato
New Zealand	Pearl Investigative Site	Newtown	Wellington
New Zealand	Pearl Investigative Site	Otahuhu	Aukland
New Zealand	Pearl Investigative Site	Tauranga
United States	Pearl Investigative Site	Abingdon	Virginia
United States	Pearl Investigative Site	Albuquerque	New Mexico
United States	Pearl Investigative Site	Anaheim	California
United States	Pearl Investigative Site	Andalusia	Alabama
United States	Pearl Investigative Site	Anderson	Indiana
United States	Pearl Investigative Site	Anniston	Alabama
United States	Pearl Investigative Site	Athens	Alabama
United States	Pearl Investigative Site	Atlanta	Georgia
United States	Pearl Investigative Site	Austell	Georgia
United States	Pearl Investigative Site	Austin	Texas
United States	Pearl Investigative Site	Avon	Indiana
United States	Pearl Investigative Site	Baltimore	Maryland
United States	Pearl Investigative Site	Bellevue	Nebraska
United States	Pearl Investigative Site	Bend	Oregon
United States	Pearl Investigative Site	Birmingham	Alabama
United States	Pearl Investigative Site	Brandon	Florida
United States	Pearl Investigative Site	Bristol	Tennessee
United States	Pearl Investigative Site	Burlington	North Carolina
United States	Pearl Investigative Site	Carlsbad	California
United States	Pearl Investigative Site	Champaign	Illinois
United States	Pearl Investigative Site	Charleston	South Carolina
United States	Pearl Investigative Site	Charlotte	North Carolina
United States	Pearl Investigative Site	Cincinnati	Ohio
United States	Pearl Investigative Site	Clearwater	Florida
United States	Pearl Investigative Site	Coeur d'Alene	Idaho
United States	Pearl Investigative Site	Colorado Springs	Colorado
United States	Pearl Investigative Site	Columbus	Georgia
United States	Pearl Investigative Site	Columbus	Ohio
United States	Pearl Investigative Site	Corning	New York
United States	Pearl Investigative Site	Danbury	Connecticut
United States	Pearl Investigative Site	Dayton	Ohio
United States	Pearl Investigative Site	Denver	Colorado
United States	Pearl Investigative Site	Dublin	Ohio
United States	Pearl Investigative Site	Duluth	Georgia
United States	Pearl Investigative Site	Easley	South Carolina
United States	Pearl Investigative Site	Edina	Minnesota
United States	Pearl Investigative Site	El Paso	Texas
United States	Pearl Investigative Site	Elwood	Indiana
United States	Pearl Investigative Site	Evanston	Illinois
United States	Pearl Investigative Site	Evansville	Indiana
United States	Pearl Investigative Site	Fort Collins	Colorado
United States	Pearl Investigative Site	Fort Worth	Texas
United States	Pearl Investigative Site	Fridley	Minnesota
United States	Pearl Investigative Site	Gaffney	South Carolina
United States	Pearl Investigative Site	Gainesville	Georgia
United States	Pearl Investigative Site	Greensboro	North Carolina
United States	Pearl Investigative Site	Greenville	South Carolina
United States	Pearl Investigative Site	Hollywood	Maryland
United States	Pearl Investigative Site	Houston	Texas
United States	Pearl Investigative Site	Huntersville	North Carolina
United States	Pearl Investigative Site	Huntsville	Texas
United States	Pearl Investigative Site	Iowa City	Iowa
United States	Pearl Investigative Site	Johnson City	Tennessee
United States	Pearl Investigative Site	Kingsport	Tennessee
United States	Pearl Investigative Site	Lafayette	Louisiana
United States	Pearl Investigative Site	Lakewood	California
United States	Pearl Investigative Site	Las Vegas	Nevada
United States	Pearl Investigative Site	Lehigh Acres	Florida
United States	Pearl Investigative Site	Livonia	Michigan
United States	Pearl Investigative Site	Longview	Texas
United States	Pearl Investigative Site	Los Angeles	California
United States	Pearl Investigative Site	Louisville	Kentucky
United States	Pearl Investigative Site	Lufkin	Texas
United States	Pearl Investigative Site	Medford	Oregon
United States	Pearl Investigative Site	Mesa	Arizona
United States	Pearl Investigative Site	Miami	Florida
United States	Pearl Investigative Site	Midvale	Utah
United States	Pearl Investigative Site	Minneapolis	Minnesota
United States	Pearl Investigative Site	Missoula	Montana
United States	Pearl Investigative Site	Monroeville	Pennsylvania
United States	Pearl Investigative Site	Morgantown	West Virginia
United States	Pearl Investigative Site	Mt. Pleasant	South Carolina
United States	Pearl Investigative Site	Murrells Inlet	South Carolina
United States	Pearl Investigative Site	Myrtle Beach	South Carolina
United States	Pearl Investigative Site	New Braunfels	Texas
United States	Pearl Investigative Site	Ocean	New Jersey
United States	Pearl Investigative Site	Omaha	Nebraska
United States	Pearl Investigative Site	Oregon	Ohio
United States	Pearl Investigative Site	Ormond Beach	Florida
United States	Pearl Investigative Site	Panama City	Florida
United States	Pearl Investigative Site	Pasadena	California
United States	Pearl Investigative Site	Pasedena	California
United States	Pearl Investigative Site	Pensacola	Florida
United States	Pearl Investigative Site	Peoria	Illinois
United States	Pearl Investigative Site	Philadelphia	Pennsylvania
United States	Pearl Investigative Site	Phoenix	Arizona
United States	Pearl Investigative Site	Portland	Oregon
United States	Pearl Investigative Site	Poway	California
United States	Pearl Investigative Site	Raleigh	North Carolina
United States	Pearl Investigative Site	Rapid City	South Dakota
United States	Pearl Investigative Site	Richmond	Virginia
United States	Pearl Investigative Site	River Forest	Illinois
United States	Pearl Investigative Site	Rock Hill	South Carolina
United States	Pearl Investigative Site	Sacramento	California
United States	Pearl Investigative Site	Salt Lake City	Utah
United States	Pearl Investigative Site	San Antonio	Texas
United States	Pearl Investigative Site	San Diego	California
United States	Pearl Investigative Site	Scottsdale	Arizona
United States	Pearl Investigative Site	South Burlington	Vermont
United States	Pearl Investigative Site	Southfield	Michigan
United States	Pearl Investigative Site	Spartanburg	South Carolina
United States	Pearl Investigative Site	Spokane	Washington
United States	Pearl Investigative Site	Springfield	Missouri
United States	Pearl Investigative Site	St Louis	Missouri
United States	Pearl Investigative Site	St. Charles	Missouri
United States	Pearl Investigative Site	St. Petersburg	Florida
United States	Pearl Investigative Site	Sunset	Louisiana
United States	Pearl Investigative Site	Tacoma	Washington
United States	Pearl Investigative Site	Tampa	Florida
United States	Pearl Investigative Site	Topeka	Kansas
United States	Pearl Investigative Site	Tucson	Arizona
United States	Pearl Investigative Site	Tullahoma	Tennessee
United States	Pearl Investigative Site	Tustin	California
United States	Pearl Investigative Site	Union	South Carolina
United States	Pearl Investigative Site	Vista	California
United States	Pearl Investigative Site	Waterbury	Connecticut
United States	Pearl Investigative Site	West Allis	Wisconsin
United States	Pearl Investigative Site	Wheat Ridge	Colorado
United States	Pearl Investigative Site	Wilmington	North Carolina
United States	Pearl Investigative Site	Winston-Salem	North Carolina
United States	Pearl Investigative Site	Winter Park	Florida
United States	Pearl Investigative Site	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Pearl Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1)		24 weeks	No
Secondary	Transition Dyspnea Index (TDI) focal score		24 weeks	No
Secondary	St. George Respiratory Questionnaire (SGRQ) score		24 weeks	No
Secondary	Rescue Ventolin hydrofluoroalkane (HFA) use		24 weeks	No
Secondary	Time to onset of action		Day 1	No
Secondary	Peak FEV1		24 weeks	No
Secondary	Change in trough FEV1 for GFF MDI and GP MDI vs. open-label tiotropium bromide inhalation powder		24 weeks	No