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

Phase 3

Completed

Conditions: Chronic Obstructive Pulmonary Disease

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

Registration Number: NCT01854645

Lead Sponsor: Pearl Therapeutics, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2103

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GFF MDI	GFF MDI	Glycopyrronium Formoterol Fumarate (GFF) Metered Dose Inhaler (MDI) (PT003)
GP MDI	GP MDI	Glycopyrronium (GP) MDI (PT001)
FF MDI	FF MDI	Formoterol Fumarate (FF) MDI (PT005)
Placebo	Placebo MDI	Placebo MDI
Open-label tiotropium bromide inhalation powder	Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®)	Open-label tiotropium bromide inhalation powder (Spiriva® Handihaler®)

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24	Baseline and at Week 24	Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1) at Week 24

Secondary Outcome Measures

Name	Time	Method
Rescue Ventolin Hydrofluoroalkane (HFA) Use	Baseline and at Week 24	Change from baseline in average daily rescue Ventolin HFA use
Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks	Baseline and Weeks 2 to 24	Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1) over 24 weeks. FEV1 was assessed at multiple time points post-baseline,and a modelbased average of all visits starting from Week 2 through week 24 inclusive was calculated. The change values reported in the table represent the change between the baseline and the average FEV1 post-baseline.
St. George's Respiratory Questionnaire (SGRQ) Score	Baseline and at Week 24	Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI 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.
Onset of Action as Assessed by FEV1	Assessed for 5- and 15-minute post dose on Day 1	Defined as the first time-point using the 5- and 15-minute post dose measurements where the difference in FEV1 from Placebo was statistically significant
Peak Change From Baseline in FEV1 Within 2 Hours Post-dose	Baseline and at Week 24	Peak change from baseline in forced expiratory volume in 1 second (FEV1) within 2 hours post-dose