Extension Study to Evaluate the Safety and Efficacy of PT003, PT001, and PT005 in Subjects With Moderate to Very Severe COPD, With Spiriva® Handihaler® (PINNACLE 3)

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

Official title:

A 28-Week, Multi-Center, Randomized, Double Blind, Parallel-Group, Active-Controlled Safety Extension Study to Evaluate the Safety and Efficacy of PT003, PT001, and PT005 in Subjects With Moderate to Very Severe COPD, With Spiriva® Handihaler® as an Active Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01970878
• Other study ID #: PT003008-00
• Status: Completed
• Phase: Phase 3
• First received: October 18, 2013
• Last updated: July 7, 2015
• Start date: November 2013
• Est. completion date: March 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

This is a multi-center, randomized, double-blind, parallel group, chronic dosing, active-controlled, 28-week safety extension study of the two pivotal 24-week safety and efficacy studies (Studies PT003006 and PT003007). This study is designed to assess the long-term safety and tolerability of Glycopyrrolate (GP) and Formoterol Fumarate (FF) combination (GFF) metered dose inhaler (MDI), GP MDI, and FF MDI in subjects with moderate to very severe COPD over a total observation period of 52 weeks. Open-label Spiriva is included as an active control. To be eligible for this study, a subject must complete participation in Study PT003006 (NCT01854645) or Study PT003007 (NCT01854658).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 893
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

Key Inclusion Criteria:

• Participant in/completion of previous 24-week PINNACLE Phase III Trial.

• 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.

• Subjects with FEV1/forced vital capacity (FVC) ratio of <0.70 and FEV1 <80% predicted normal and =750 mL if FEV1 <30% of predicted normal value.

• 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 electrocardiogram (ECG)

• Abnormal liver function tests defined as alanine transaminase (ALT), aspartate transaminanse (AST), 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 (COPD)
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• GFF MDI (PT 003)
GFF MDI administered as two puffs BID
• GP MDI (PT001)
GP MDI administered as two puffs BID
• FF MDI (PT005)
FF MDI administered as two puffs BID
• Open-label tiotropium bromide inhalation (Spiriva® Handihaler®)
Taken as 1 capsule daily containing 18 µg of open-label tiotropium via the Handihaler dry powder inhaler (DPI)

Locations

Country	Name	City	State
Australia	Pearl Investigative Site	Adelaide	South Australia
Australia	Pearl Investigative Site	Brisbane	Queensland
Australia	Pearl Investigative Site	Cairns	Queensland
Australia	Pearl Investigative Site	Heidelberg	Victoria
Australia	Pearl Investigative Site	Nederlands	Western Australia
Australia	Pearl Investigative Site	New Lambton	New South Wales
Australia	Pearl Investigative Site	Perth	Western 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	Greenlabe	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	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	Bellvue	Nebraska
United States	Pearl Investigative Site	Bend	Oregon
United States	Pearl Investigative Site	Birmingham	Alabama
United States	Pearl Investigative Site	Brandon	Oregon
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	Chesterfield	Missouri
United States	Pearl Investigative Site	Cincinnati	Ohio
United States	Pearl Investigative Site	Clearwater	Florida
United States	Pearl Investigative Site	Colorado Springs	Colorado
United States	Pearl Investigative Site	Columbus	Georgia
United States	Pearl Investigative Site	Corning	New York
United States	Pearl Investigative Site	Couer d'aline	Idaho
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	Duluth	Georgia
United States	Pearl Investigative Site	Easley	South Carolina
United States	Pearl Investigative Site	Edina	Minnesota
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	Fridley	Minnesota
United States	Pearl Investigative Site	Gaffney	South Carolina
United States	Pearl Investigative Site	Gainesville	Georgia
United States	Pearl Investigative Site	Glendale	Arizona
United States	Pearl Investigative Site	Greensboro	North 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	Jasper	Alabama
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	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	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	Monterey Park	California
United States	Pearl Investigative Site	Mooresville	North Carolina
United States	Pearl Investigative Site	Morgantown	West Virginia
United States	Pearl Investigative Site	Murrells Inlet	South Carolina
United States	Pearl Investigative Site	New Braunfels	Texas
United States	Pearl Investigative Site	Olathe	Kansas
United States	Pearl Investigative Site	Omaha	Nebraska
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	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	Pittsburgh	Pennsylvania
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 Bend	Indiana
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 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	Tustin	California
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	Overall safety and tolerability will be evaluated using adverse events, vital sign measurements, 12-lead ECG parameters, and clinical laboratory parameters.		52 weeks	Yes
Primary	Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1)		52 weeks	No
Secondary	Transition Dyspnea Index (TDI) score		52 Weeks	No
Secondary	Peak change from baseline in FEV1		52 Weeks	No
Secondary	Change from baseline in St. George Respiratory Questionnaire (SGRQ) total score		52 Weeks	No
Secondary	Change from baseline in Daily rescue Ventolin hydrofluoroalkane (HFA) use		52 Weeks	No