Clinical trial NCT01566773: PT001 MDI Versus Spiriva® in Patients With Moderate to Severe COPD
Official title: A Randomized, Double Blind (Test Products and Placebo), Chronic Dosing (14 Days), Four Period, Eight Treatment, Placebo-Controlled, Incomplete Block, Cross Over, Multi Center Study to Assess Efficacy and Safety of Six Doses of PT001 in Patients With Moderate to Severe COPD, Compared With Spiriva® Handihaler® (Tiotropium Bromide, Open Label) as An Active Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2012-03-29
Enrollment: 140
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The overall objective of this study is to determine an optimal dose and dosing regimen of PT001 MDI for further evaluation in later stage studies.

Detailed description: The primary objective of this study is to assess efficacy relative to placebo of GP MDI in subjects with moderate to severe chronic obstructive pulmonary disease (COPD) within the range of doses evaluated in this protocol. To this end, each dose of GP MDI will be compared to placebo with respect to the primary efficacy endpoint, FEV1 AUC0-12 relative to baseline.

Eligibility criteria: 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 inclusion/exclusion criteria as defined in the protocol

Primary outcomes:
measure: FEV1 AUC0-12
timeFrame: Day 14 (-1 hr, -30 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 11.5 hr, 12 hr)
Secondary outcomes:
measure: Peak Change From Baseline in FEV1
timeFrame: Day 1
measure: Time to Onset of Action (>10% Improvement in FEV1) on Day 1
timeFrame: Day 1 (15 min, 30 min, 1 hr, 2 hrs, no onset within 2 hrs)
measure: Percentage of Subjects Achieving at Least 12% Improvement in FEV1
timeFrame: Day 1
measure: Peak Change From Baseline in Inspiratory Capacity (IC)
timeFrame: Day 1 (1 hr and 2 hr post-dose )
measure: Change From Baseline in Morning Pre-dose Trough FEV1
timeFrame: Day 7 (average of the 60 and 30-minute pre-dose values on Treatment Day 7 minus the baseline)
measure: Peak Change From Baseline in FEV1
timeFrame: Day 7
measure: Change From Baseline in Morning Pre-dose Trough Inspiratory Capacity (IC)
timeFrame: Day 7
measure: Peak Change From Baseline in IC
timeFrame: Day 7 (mean of 1 hr and 2 hr post-dose assessments)
measure: Change From Baseline in Mean Morning Pre-dose Daily PEFR
timeFrame: Day 7 (60 minutes pre-dose, 30 minutes pre-dose)
measure: Change From Baseline in Morning Post-dose Daily PEFR
timeFrame: Day 7 (30 minutes post-dose)
measure: Change From Baseline in Mean Evening Pre-dose PEFR
timeFrame: Day 7
measure: Change From Baseline in Mean Evening Post-dose PEFR
timeFrame: Day 7
measure: Mean Number of Puffs of Rescue Medication
timeFrame: Day 7
measure: Change From Baseline in Morning Pre-dose Trough FEV1
timeFrame: Day 14 (average of the 60 and 30-minute pre-dose values on Treatment Day 14 minus the baseline)
measure: Peak Change From Baseline in FEV1
timeFrame: Day 14
measure: Change From Baseline for Mean Morning Pre-dose Trough IC
timeFrame: Day 14 (average of the 60 and 30-minute pre-dose assessments minus the baseline)
measure: Peak Change From Baseline in IC
timeFrame: Day 14 (mean of 1 and 2 hour post-dose assessments minus the baseline)
measure: Change From Baseline in 12-hour Post-dose Trough FEV1
timeFrame: Day 14 (Baseline, 11.5 and 12 hours post dose)
measure: Change From Baseline in Mean Morning Pre-dose Daily PEFR
timeFrame: Baseline, Treatment Day 1 and every day, to the end of the 14-Day Treatment period before dosing, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7)
measure: Change From Baseline in Mean Morning Post-dose Daily PEFR
timeFrame: Baseline, Treatment Day 1 and every day, to the end of the 14-Day Treatment period 30 minutes post dosing, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7)
measure: Change From Baseline in Mean Evening Pre-dose Daily PEFR
timeFrame: Treatment Day 1 to the end of the 14-Day Treatment, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7)
measure: Change From Baseline in Mean Evening Post-dose Daily PEFR
timeFrame: Through the end of the 14-Day Treatment
measure: Mean Number of Puffs of Rescue Medication (End of Treatment)
timeFrame: Day 14 (End of treatment)
measure: Change From Baseline in Morning Pre-dose Trough FEV1 (mL) Averaging Treatment Day 7 and Day 14
timeFrame: Day 1 through Day 14
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Pearl Investigative Site
state: California
city: Clearwater
country: United States
facility: Pearl Investigative Site
state: Florida
city: Panama City
country: United States
facility: Pearl Investigative Site
state: Florida
city: Tampa
country: United States
facility: Pearl Investigative Site
state: Florida
city: Winter Park
country: United States
facility: Pearl Investigative Site
state: Florida
city: Charlotte
country: United States
facility: Pearl Investigative Site
state: North Carolina
city: Medford
country: United States
facility: Pearl Investigative Site
state: Oregon
city: Spartanburg
country: United States
facility: Pearl Investigative Site
state: South Carolina
city: Longview
country: United States
facility: Pearl Investigative Site
state: Texas
city: Richmond
country: United States
facility: Pearl Investigative Site
state: Virginia
Study officials:
affiliation: Pearl Therapeutics, Inc.
name: Colin Reisner, MD
role: STUDY_DIRECTOR
References:
citation: Fabbri LM, Kerwin EM, Spangenthal S, Ferguson GT, Rodriguez-Roisin R, Pearle J, Sethi S, Orevillo C, Darken P, St Rose E, Fischer T, Golden M, Dwivedi S, Reisner C. Dose-response to inhaled glycopyrrolate delivered with a novel Co-Suspension Delivery Technology metered dose inhaler (MDI) in patients with moderate-to-severe COPD. Respir Res. 2016 Sep 2;17(1):109. doi: 10.1186/s12931-016-0426-4.