Efficacy and Safety Study of PT009, PT008, and PT005 in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

A Randomized, Double Blind, Chronic Dosing (28 Days), Four Period, Five Treatment, Incomplete Block, Multi Center, Crossover Study to Assess the Efficacy and Safety of PT009, PT008, and PT005 in Subjects With Moderate to Severe COPD

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02196077

Acronym

PT009001

Enrollment

180

Registered

2014-07-21

Start date

2014-08-01

Completion date

2015-03-01

Last updated

2018-06-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Budesonide and formoterol inhalation aerosol

Brief summary

This is a Phase IIb, randomized, double blind, chronic dosing (28 days), four period, five treatment, incomplete block, crossover design in subjects with moderate to severe COPD. The overall objective is to demonstrate that the combination of budesonide (BD; PT008) and formoterol fumarate (FF; PT005) in a metered-dose inhaler (MDI); (BFF MDI; PT009) provides benefit on lung function compared with BD MDI in subjects with moderate to severe COPD.

Interventions

DRUGBFF MDI 320/9.6 μg

Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 320/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)

DRUGBFF MDI 160/9.6 μg

Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 160/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)

DRUGBFF MDI 80/9.6 μg

Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 80/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)

DRUGBD MDI 320 μg

Budesonide metered dose inhaler (BD MDI) 320 μg; PT008 administered as 2 inhalations, twice daily (BID)

DRUGFF MDI 9.6 μg

Formoterol fumarate metered dose inhaler (FF MDI) 9.6 μg; PT005 administered as 2 inhalations, twice daily (BID)

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

Double Blind

Eligibility

Sex/Gender

ALL

Age

40 Years to 80 Years

Healthy volunteers

Inclusion criteria

* Informed Consent Form (ICF) prior to any study related procedures * COPD Diagnosis: Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) * Tobacco Use: Current or former smokers with a history of at least 10 pack years of cigarette smoking * Women of non-childbearing potential or medically acceptable contraception for women of child-bearing potential and males with female partners of childbearing potential * Severity of Disease: Subjects with an established clinical history of COPD and severity defined as: FEV1/forced vital capacity (FVC) ratio of \<0.70; At Screening (Visit 1a/b), post bronchodilator FEV1 must be \<80% predicted normal value, calculated using NHANES III (Third National Health and Nutrition Examination Survey) reference equations; the measured FEV1 must also be ≥30% of predicted normal value; at Visit 2, the average of the 60 minutes and 30 minutes pre dose FEV1 assessments must be \<80% predicted normal value calculated using NHANES III reference equations * Screening clinical laboratory tests must be acceptable to the Investigator * Screening ECG must be acceptable to the Investigator * Chest x ray or computerized tomography (CT) scan within 6 months prior to Visit 1a must be acceptable to the Investigator.

Exclusion criteria

* Significant diseases other than COPD, ie., disease or condition 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 * Pregnancy, nursing female subjects, or subjects trying to conceive, or not using medically acceptable form of contraception * Asthma: Subjects who have a primary diagnosis of asthma (Note: Subjects with a prior history of asthma are eligible if COPD is currently their primary diagnosis). * Alpha 1 Antitrypsin Deficiency: Subjects who have alpha 1 antitrypsin deficiency as the cause of COPD -Active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease, and uncontrolled sleep apnea (ie., in the opinion of the Investigator severity of the disorder would impact the conduct of the study)- * Clinically significant neurologic, cardiovascular, hepatic, renal, endocrinologic, pulmonary, hematological, psychiatric, or other medical illness that would interfere with participation in this study * Poorly Controlled COPD * History of ECG abnormalities * Cancer not in complete remission for at least 5 years * Clinically significant, symptomatic prostatic hypertrophy * Male subjects with a trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to Screening * Clinically significant bladder neck obstruction or urinary retention * Inadequately treated glaucoma * History of an allergic reaction or hypersensitivity to any drug or to any component of the formulations used in this study

Design outcomes

Primary

Measure	Time frame	Description
FEV1 AUC0-12 on Day 29	Day 29	Change from Baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12)

Secondary

Measure	Time frame	Description
Peak Change From Baseline in FEV1 (in Liters) Day 15	Day 15	—
Peak Change From Baseline in FEV1 (in Liters) Day 29	Day 29	—
Peak Change From Baseline in FEV1 on Day 1	Day 1	—
Change From Baseline in Morning Pre-dose Trough FEV1 Over 28 Days	Over 28 days	—
Transition Dyspnea Index (TDI) Focal Score on Day 29	Day 29	Min/Max Range of TDI scale -9 (major deterioration) to +9 (major improvement)
Change From Baseline in Average Daily Use of Rescue Ventolin HFA Over the Last Week of Treatment	Visit 12-13 (7 days)	—
Forced Vital Capacity (FVC) AUC0-12 on Day 29	Day 29	—

Countries

United States

Participant flow

Recruitment details

This study was conducted at 20 sites in the United States from August 2014 to March 2015. Study participation was a maximum of 28 days.

Pre-assignment details

A Randomized, Double-Blind, Chronic Dosing (28 Days), Four-Period, Five-Treatment, Incomplete Block, Multi-Center, Crossover Study. Subjects completed final visit procedures. Final telephone follow-up occurred between 7 to 14 days from Visit 13. By-sequence tabulations of the data were not pre-specified.

Participants by arm

Arm	Count
Subjects	180
Total	180

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	4
Overall Study	Lack of Efficacy	1
Overall Study	Lost to Follow-up	3
Overall Study	Physician Decision	1
Overall Study	Protocol Violation	24
Overall Study	Withdrawal by Subject	14

Baseline characteristics

Characteristic	Subjects
Age, Continuous	62.2 Years STANDARD_DEVIATION 8.4
Sex: Female, Male Female	96 Participants
Sex: Female, Male Male	84 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	12 / 155	2 / 106	5 / 103	8 / 108	8 / 157
serious Total, serious adverse events	4 / 155	2 / 106	3 / 103	4 / 108	2 / 157

Outcome results

Primary

FEV1 AUC0-12 on Day 29

Change from Baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12)

Time frame: Day 29

Population: MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
BFF MDI 320/9.6 ug	FEV1 AUC0-12 on Day 29	0.231 Liters
BFF MDI 160/9.6 ug	FEV1 AUC0-12 on Day 29	0.197 Liters
BFF MDI 80/9.6 ug	FEV1 AUC0-12 on Day 29	0.205 Liters
BD MDI 320 ug	FEV1 AUC0-12 on Day 29	0.011 Liters
FF MDI 9.6 ug	FEV1 AUC0-12 on Day 29	0.176 Liters

Secondary