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

Pearl Therapeutics

Status and phase: Completed; Phase 3

Conditions: Chronic Obstructive Pulmonary Disease

Treatments: Drug: GP MDI; Drug: FF MDI; Drug: Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®); Drug: Placebo MDI; Drug: GFF MDI

Study type: Interventional

Funder types: Industry

Identifiers

NCT01854645

PT003006-00

Details and patient eligibility

About

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.

Enrollment: 2,103 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 β2-agonists, glycopyrronium or other muscarinic anticholinergics, lactose/milk protein or any component of the MDI

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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2,103 participants in 5 patient groups, including a placebo group

GFF MDI

Experimental group

Description:

Glycopyrronium Formoterol Fumarate (GFF) Metered Dose Inhaler (MDI) (PT003)

Treatment:

Drug: GFF MDI

GP MDI

Experimental group

Description:

Glycopyrronium (GP) MDI (PT001)

Treatment:

Drug: GP MDI

FF MDI

Experimental group

Description:

Formoterol Fumarate (FF) MDI (PT005)

Treatment:

Drug: FF MDI

Open-label tiotropium bromide inhalation powder

Active Comparator group

Description:

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

Treatment:

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

Placebo

Placebo Comparator group

Description:

Placebo MDI

Treatment:

Drug: Placebo MDI