A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® (Kronos) (KRONOS)

Pearl Therapeutics

Status and phase: Completed; Phase 3

Conditions: COPD

Treatments: Drug: BFF MDI (PT009) 320/9.6 μg; Drug: Symbicort® Turbuhaler® (TBH) Inhalation Powder; Drug: GFF MDI (PT003) 14.4/9.6 μg; Drug: BGF MDI 320/14.4/9.6 μg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02497001

PT010006

Details and patient eligibility

About

Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® in Subjects with Moderate to Very Severe Chronic Obstructive Pulmonary Disease.

Full description

A Randomized, Double-Blind, Parallel-Group, 24-Week, Chronic-Dosing, Multi-Center Study to Assess the Efficacy and Safety of PT010, PT003, and PT009 Compared With Symbicort® Turbuhaler® as an Active Control in Subjects with Moderate to Very Severe Chronic Obstructive Pulmonary Disease

This study includes the following 3 sub-studies: 12-hour Pulmonary Function Test (PFT), Pharmacokinetic (PK) Profile, and Hypothalamic-pituitary-adrenal Axis.

Enrollment: 1,902 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Given their signed written informed consent to participate.
• Non-child bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or Child bearing potential, has a negative serum pregnancy test at Visit 1, and agrees to acceptable contraceptive methods used consistently and correctly for the duration of the study.
• Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS), or other local applicable guidelines.
• Current or former smokers with a history of at least 10 pack-years of cigarette smoking.
• Forced expiratory volume in 1 second (FEV1)/Forced vital capacity (FVC) ratio must be <0.70 and FEV1 must be <80% predicted normal value calculated using NHANES III reference equations (or reference norms applicable to other regions).
• Required COPD maintenance therapy:
• All Subjects must have been on two or more inhaled maintenance therapies for the management of their COPD for at least 6 weeks prior to Screening. Scheduled SABA and/or scheduled SAMA are considered inhaled maintenance therapies

Please refer to the study protocol for the complete inclusion criteria list.

Exclusion Criteria

• Significant diseases or conditions other than COPD, which, in the opinion of the Investigator, may put the subject 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.
• Women who are pregnant or lactating, or are planning to become pregnant during the course of the study, or women of childbearing potential who are not using an acceptable method of contraception.
• Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma.
• Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Visit 1 (Screening) or during the Screening Period
• Subjects who have poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to Visit 1 (Screening) or during the Screening Period
• Immune suppression or severe neurological disorders affecting control of the upper airway or other risk factors that in the opinion of the Investigator would put the subject at substantial risk of pneumonia.
• Subjects with a diagnosis of narrow angle glaucoma, who, in the opinion of the Investigator, have not been adequately treated.
• Subjects who have a history of hypersensitivity to β2-agonists, budesonide or any other corticosteroid components, glycopyrronium or other muscarinic anticholinergics, or any other component of the IMPs.

Please refer to the study protocol for the complete inclusion criteria list.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,902 participants in 4 patient groups

BGF MDI (PT010) 320/14.4/9.6 μg ex-actuator

Experimental group

Description:

BGF MDI 320/14.4/9.6 μg,Budesonide, Glycopyrronium, Formoterol Fumarate Inhalation Aerosol

Treatment:

Drug: BGF MDI 320/14.4/9.6 μg

GFF MDI (PT003) 14.4/9.6 μg ex-actuator

Experimental group

Description:

GFF MDI 14.4/9.6 μg ex-actuator Glycopyrronium, Formoterol Fumarate Inhalation Aerosol

Treatment:

Drug: GFF MDI (PT003) 14.4/9.6 μg

BFF MDI (PT009) 320/9.6 μg ex-actuator

Experimental group

Description:

BFF MDI 320/9.6 μg, Budesonide, Formoterol Fumarate Inhalation Aerosol

Treatment:

Drug: BFF MDI (PT009) 320/9.6 μg

Symbicort

Active Comparator group

Description:

Symbicort® Turbuhaler® (TBH) Inhalation Powder 200/6 μg

Treatment:

Drug: Symbicort® Turbuhaler® (TBH) Inhalation Powder