Study to Evaluate the Efficacy, Safety and Pharmacokinetics of PT001, PT003, and PT005 Following Chronic Dosing (7 Days) in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)

A Randomized, Double-Blind (Test Products and Placebo), Chronic Dosing (7 Days), Four-Period, Eight-Treatment, Placebo-Controlled, Incomplete Block, Cross-Over, Multi-Center Study to Assess Efficacy and Safety of Two Doses of PT003, Two Doses of PT005 and One Dose of PT001 in Patients With Moderate to Very Severe COPD, Compared With Foradil® Aerolizer® (12 μg, Open-Label) and Spiriva® Handihaler® (18 μg, Open-Label) as Active Controls

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01085045

Enrollment

118

Registered

2010-03-11

Start date

2010-03-31

Completion date

2010-11-30

Last updated

2017-04-26

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

COPD

Brief summary

The purpose of this study is to evaluate, after 1 week of dosing, the efficacy and safety of PT003 compared with its individual components (PT001 and PT005), placebo and two active comparators to demonstrate superiority of the combination to its components, and to assess the relative contribution of the components compared with placebo, in patients with moderate to very severe COPD.

Interventions

DRUGPT003 MDI

Inhaled PT003 MDI administered as two puffs BID for 7 days

DRUGPT005 MDI

Inhaled PT005 MDI administered as two puffs BID for 7 days

DRUGPlacebo MDI

Inhaled placebo administered as two puffs BID for 7 days

DRUGTiotropium bromide 18 μg (Spiriva Handihaler®)

Inhaled tiotropium bromide 18 μg (Spiriva Handihaler®) administered QD for 7 days

DRUGFormoterol Fumarate 12 μg (Foradil® Aerolizer®)

Inhaled formoterol fumarate 12 μg (Foradil® Aerolizer®) administered BID for 7 days

DRUGPT001 MDI

Inhaled PT001 MDI administered as two puffs BID for 7 days

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 80 Years

Healthy volunteers

Inclusion criteria

* Signed written informed consent * 40 - 80 years of age * Clinical history of COPD with airflow limitation that is not fully reversible * Females of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods * Current/former smokers with at least a 10 pack-year history of cigarette smoking * A measured post- bronchodilator FEV1/FVC ratio of \< or = 0.70 * A measured post- bronchodilator FEV1 \> or = 750ml or 30% predicted and \< or = 80% of predicted normal values * Able to change COPD treatment as required by protocol

Exclusion criteria

* Women who are pregnant or lactating * Primary diagnosis of asthma * Alpha-1 antitrypsin deficiency as the cause of COPD * Active pulmonary diseases * Prior lung volume reduction surgery * Abnormal chest X-ray (or CT scan) not due to the presence of COPD * Hospitalized due to poorly controlled COPD within 3 months of Screening * Clinically significant medical conditions that preclude participation in the study (e.g. clinically significant abnormal ECG, uncontrolled hypertension, glaucoma, symptomatic prostatic hypertrophy) * Cancer that has not been in complete remission for at least 5 years * Treatment with investigational study drug or participation in another clinical trial or study within the last 30 days or 5 half lives Other protocol defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
FEV1 AUC 0-12 on Day 7	Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 11.5, and 12 hours post-dose on Day 7	Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 (normalized) relative to baseline FEV1 following 7-day dose administration

Secondary

Measure	Time frame	Description
12 hr Post-dose Trough FEV1 on Day 7	Day 7	12 hour post-dose trough Forced Expiratory Volume in 1 second on Day 7
Change From BL in Mean Morning Pre-dose Daily Peak Flow Rate on Day 7	Day 7	Change from BaseLine in mean morning pre-dose daily peak flow rate on Day 7
Peak Change From BL in FEV1 on Day 1	Day 1	Peak change from Baseline in FEV1 on Day 1
Peak Change From BL in FEV1 on Day 7	Day 7	Peak change from Baseline (BL) in FEV1 on Day 7
Peak Change From BL in Inspiratory Capacity on Day 1	Day 1	Peak change from Baseline in Inspiratory Capacity (IC) on Day 1
Change in Morning Pre-dose FEV1 on Day 7	Day 7	Change from Baseline in morning pre-dose FEV1 on Day 7
Time to Onset of Action >=10% Improvement in FEV1 on Day 1	Day 1	Time to Onset of Action where the improvement in FEV1 on Day 1 was \>=10%
Percentage of Patients Achieving >=12% Improvement in FEV1 on Day 1	Day 1	Time to Onset of Action where the improvement in FEV1 on Day 1 was \>= 12%
Change From BL in Mean Morning Post-dose Daily Peak Flow Rate on Day 7	Day 7	Change from BaseLine in mean morning post-dose daily peak flow rate on Day 7
Change From BL in Mean Evening Pre-dose Daily Peak Flow Rate on Day 7	Day 7	Change from BaseLine in mean evening pre-dose daily peak flow rate on Day 7
Change From BL in Mean Evening Post-dose Daily Peak Flow Rate on Day 7	Day 7	Change from BaseLine in mean evening post-dose daily peak flow rate on Day 7
Peak Change From BL IC on Day 7	Day 7	Peak Change from Baseline Inspiratory Capacity on following 7-day dose administration

Countries

Australia, New Zealand, United States

Participant flow

Recruitment details

Conducted at 16 sites in Australia, New Zealand and the US from 24 March 2010 -28 October 2010. The entire study period was a maximum of 20 weeks. Chronic dosing (7 days), 4-period, 8-treatment, incomplete block, cross-over conducted in two parts.

Pre-assignment details

Part A: 4-period, 8-treatment, incomplete block cross-over. Subjects randomized to 1 of 48 sequences, each subject received 4 of 8 possible treatments. Part B: 4-period, 4-treatment, full cross-over. Each subject randomized to 1 of 24 sequences and each sequence was assigned to at least 1 subject.

Participants by arm

Arm	Count
All Subjects All Baseline Subjects	122
Total	122

Withdrawals & dropouts

Period	Reason	FG000
Part A	Adverse Event	6
Part A	Protocol Specified Criteria	7
Part A	Protocol Violation	1
Part A	Withdrawal by Subject	4
Part B	Adverse Event	6
Part B	Lost to Follow-up	1
Part B	Protocol Specified Criteria	6
Part B	Withdrawal by Subject	2

Baseline characteristics

Characteristic	All Subjects
Age, Continuous	63.4 Years STANDARD_DEVIATION 8.92
Sex: Female, Male Female	53 Participants
Sex: Female, Male Male	69 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	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	14 / 41	17 / 43	10 / 41	9 / 58	5 / 64	4 / 64	4 / 52	7 / 55
serious Total, serious adverse events	0 / 41	1 / 43	0 / 41	2 / 58	1 / 64	2 / 64	0 / 52	0 / 55

Outcome results

Primary

FEV1 AUC 0-12 on Day 7

Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 (normalized) relative to baseline FEV1 following 7-day dose administration

Time frame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 11.5, and 12 hours post-dose on Day 7

Population: Modified Intent to Treat (MITT) Population - not including the 4 sentinel patients.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
GFF MDI 72/9.6 μg	FEV1 AUC 0-12 on Day 7	1.537 Liters
GFF MDI 36/9.6 μg	FEV1 AUC 0-12 on Day 7	1.529 Liters
GP MDI 36 μg	FEV1 AUC 0-12 on Day 7	1.429 Liters
Spiriva 18 μg	FEV1 AUC 0-12 on Day 7	1.434 Liters
FF MDI 9.6 μg	FEV1 AUC 0-12 on Day 7	1.421 Liters
FF MDI 7.2 μg	FEV1 AUC 0-12 on Day 7	1.413 Liters
Foradil 12 μg	FEV1 AUC 0-12 on Day 7	1.437 Liters

Secondary