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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01854645




Registration number
NCT01854645
Ethics application status
Date submitted
13/05/2013
Date registered
15/05/2013
Date last updated
28/03/2017

Titles & IDs
Public title
Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD); (PINNACLE 1)
Scientific 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
Secondary ID [1] 0 0
PT003006-00
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GFF MDI
Treatment: Drugs - GP MDI
Treatment: Drugs - FF MDI
Treatment: Drugs - Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®)
Treatment: Drugs - Placebo MDI

Experimental: GFF MDI - Glycopyrronium Formoterol Fumarate (GFF) Metered Dose Inhaler (MDI) (PT003)

Experimental: GP MDI - Glycopyrronium (GP) MDI (PT001)

Experimental: FF MDI - Formoterol Fumarate (FF) MDI (PT005)

Active comparator: Open-label tiotropium bromide inhalation powder - Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®)

Placebo comparator: Placebo - Placebo MDI


Treatment: Drugs: GFF MDI
GFF MDI administered as two puffs Bis in Di.e. Twice Daily (BID)

Treatment: Drugs: GP MDI
GP MDI administered as two puffs BID

Treatment: Drugs: FF MDI
FF MDI administered as two puffs BID

Treatment: Drugs: 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)

Treatment: Drugs: Placebo MDI
Inhaled placebo administered as two puffs BID
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24
Timepoint [1] 0 0
Baseline and at Week 24
Secondary outcome [1] 0 0
Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks
Timepoint [1] 0 0
Baseline and Weeks 2 to 24
Secondary outcome [2] 0 0
St. George's Respiratory Questionnaire (SGRQ) Score
Timepoint [2] 0 0
Baseline and at Week 24
Secondary outcome [3] 0 0
Rescue Ventolin Hydrofluoroalkane (HFA) Use
Timepoint [3] 0 0
Baseline and at Week 24
Secondary outcome [4] 0 0
Onset of Action as Assessed by FEV1
Timepoint [4] 0 0
Assessed for 5- and 15-minute post dose on Day 1
Secondary outcome [5] 0 0
Peak Change From Baseline in FEV1 Within 2 Hours Post-dose
Timepoint [5] 0 0
Baseline and at Week 24

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2015
Sample size
Target
Accrual to date
Final
2103
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Pearl Investigative Site - New Lambton
Recruitment hospital [2] 0 0
Pearl Investigative Site - Westmead
Recruitment hospital [3] 0 0
Pearl Investigative Site - Brisbane
Recruitment hospital [4] 0 0
Pearl Investigative Site - Cairns
Recruitment hospital [5] 0 0
Pearl Investigative Site - Wooloongabba
Recruitment hospital [6] 0 0
Pearl Investigative Site - Adelaide
Recruitment hospital [7] 0 0
Pearl Investigative Site - Daw Park
Recruitment hospital [8] 0 0
Pearl Investigative Site - Toorak Gardens
Recruitment hospital [9] 0 0
Pearl Investigative Site - Box Hill
Recruitment hospital [10] 0 0
Pearl Investigative Site - Heidelberg
Recruitment hospital [11] 0 0
Pearl Investigative Site - Nedlands
Recruitment hospital [12] 0 0
Pearl Investigative Site - Perth
Recruitment postcode(s) [1] 0 0
- New Lambton
Recruitment postcode(s) [2] 0 0
- Westmead
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment postcode(s) [4] 0 0
- Cairns
Recruitment postcode(s) [5] 0 0
- Wooloongabba
Recruitment postcode(s) [6] 0 0
- Adelaide
Recruitment postcode(s) [7] 0 0
- Daw Park
Recruitment postcode(s) [8] 0 0
- Toorak Gardens
Recruitment postcode(s) [9] 0 0
- Box Hill
Recruitment postcode(s) [10] 0 0
- Heidelberg
Recruitment postcode(s) [11] 0 0
- Nedlands
Recruitment postcode(s) [12] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Arizona
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United States of America
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California
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Colorado
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Connecticut
Country [6] 0 0
United States of America
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Florida
Country [7] 0 0
United States of America
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Georgia
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United States of America
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Idaho
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Illinois
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United States of America
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Indiana
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United States of America
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Iowa
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United States of America
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Kansas
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United States of America
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Kentucky
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United States of America
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Louisiana
Country [15] 0 0
United States of America
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Maryland
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United States of America
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Michigan
Country [17] 0 0
United States of America
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Minnesota
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United States of America
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Missouri
Country [19] 0 0
United States of America
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Montana
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United States of America
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Nebraska
Country [21] 0 0
United States of America
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Nevada
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United States of America
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New Jersey
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United States of America
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New Mexico
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United States of America
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New York
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North Carolina
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Ohio
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Oregon
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United States of America
State/province [28] 0 0
Pennsylvania
Country [29] 0 0
United States of America
State/province [29] 0 0
South Carolina
Country [30] 0 0
United States of America
State/province [30] 0 0
South Dakota
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United States of America
State/province [31] 0 0
Tennessee
Country [32] 0 0
United States of America
State/province [32] 0 0
Texas
Country [33] 0 0
United States of America
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Utah
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United States of America
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Vermont
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United States of America
State/province [35] 0 0
Virginia
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United States of America
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Washington
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West Virginia
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United States of America
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Wisconsin
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New Zealand
State/province [39] 0 0
Aukland
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New Zealand
State/province [40] 0 0
Dunedin
Country [41] 0 0
New Zealand
State/province [41] 0 0
East Aukland
Country [42] 0 0
New Zealand
State/province [42] 0 0
Waikato
Country [43] 0 0
New Zealand
State/province [43] 0 0
Wellington
Country [44] 0 0
New Zealand
State/province [44] 0 0
Tauranga

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pearl Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT01854645
Trial related presentations / 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.
Martinez FJ, Lipworth BJ, Rabe KF, Collier DJ, Ferguson GT, Sethi S, Feldman GJ, O'Brien G, Jenkins M, Reisner C. Benefits of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) in improving lung function and reducing exacerbations in patients with moderate-to-very severe COPD: a pooled analysis of the PINNACLE studies. Respir Res. 2020 May 25;21(1):128. doi: 10.1186/s12931-020-01388-y.
Martinez FJ, Rabe KF, Lipworth BJ, Arora S, Jenkins M, Martin UJ, Reisner C. Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Lung Function versus Monotherapies in GOLD Category A Patients with COPD: Pooled Data from the Phase III PINNACLE Studies. Int J Chron Obstruct Pulmon Dis. 2020 Jan 9;15:99-106. doi: 10.2147/COPD.S229794. eCollection 2020.
Martinez FJ, Fabbri LM, Ferguson GT, Orevillo C, Darken P, Martin UJ, Reisner C. Baseline Symptom Score Impact on Benefits of Glycopyrrolate/Formoterol Metered Dose Inhaler in COPD. Chest. 2017 Dec;152(6):1169-1178. doi: 10.1016/j.chest.2017.07.007. Epub 2017 Jul 16.
Public notes

Contacts
Principal investigator
Name 0 0
Colin Reisner, MD
Address 0 0
Pearl Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01854645