Study to Evaluate the Safety and Efficacy of Inhaled PT001 in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Phase 1

Completed

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: Tiotropium Handihaler; Drug: Inhaled PT001; Drug: Inhaled Placebo

• Registration Number: NCT00871182
• Lead Sponsor: Pearl Therapeutics, Inc.

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of inhaled PT001 compared to placebo and tiotropium in patients with mild to moderate chronic obstructive pulmonary disease (COPD).

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03
• Study First Submitted: 2009-03-26
• Study First Submitted QC: 2009-03-27
• Study First Posted: 2009-03-30
• Primary Completion: 2009-09
• Study Completion: 2009-09
• Disposition First Submitted: 2010-08-24
• Disposition First Submitted QC: 2010-08-24
• Disposition First Posted: 2010-08-27
• Status Verified: 2013-06
• Last Update Submitted: 2013-06-12
• Last Update Posted: 2013-06-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

• Signed written informed consent
• 40 - 75 years of age
• Females of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods
• COPD diagnosis
• Current/former smokers with at least a 10 pack-year history of cigarette smoking
• Patients with established clinical history of COPD and severity defined as a post-ipratropium FEV1/FVC ratio of ≤0.70 and FEV1 ≥50 and ≤85% of predicted normal at Screening
• Must demonstrate reversibility to ipratropium demonstrated by a >200 mL improvement over baseline and/or >12% and >150 mL improvement over baseline
• Patients willing to stay at study site for at least 24 hours on each test day

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 24 weeks of Screening
• Unable to perform acceptable spirometry
• Poorly controlled COPD in prior 6-weeks, defined as the occurrence of acute worsening of COPD requiring corticosteroids or antibiotics or acute worsening of COPD requiring treatment prescribed by a physician
• Clinically significant medical conditions
• Symptomatic prostatic hypertrophy or bladder neck obstruction
• Known narrow-angle glaucoma
• Lower respiratory tract infection requiring antibiotics in past 6 weeks
• Clinically significant abnormal ECG
• Clinically significant uncontrolled hypertension
• Positive Hepatitis B surface antigen or Hepatitis C antibody
• Cancer that has not been in complete remission for at least 5 years
• History of hypersensitivity to any beta2-agonists or anticholinergics
• History of severe milk protein allergy
• Known or suspected history of alcohol or drug abuse
• Medically unable to withhold short acting bronchodilators for 6-hours
• Use of the medications below in specified time interval prior to Screening: 3 months: depot corticosteroids, intra-articular corticosteroids; 6 weeks: oral corticosteroids, antibiotics administered for a COPD exacerbation; and 1 month: P-glycoprotein inhibitors, CYP450 3A4 inhibitors, ICS >1000 μg/day of fluticasone propionate or equivalent
• The following COPD medications need to be stopped and switched to appropriate replacement therapies: tiotropium, oral beta2 agonists, LABAs, combination corticosteroid/LABAs, theophylline, leukotriene inhibitors,cromoglycate and nedocromil
• Use of the following medications is prohibited: tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, beta-adrenergic antagonists, anticonvulsants (barbiturates, hydantoins, and carbamazepine and phenothiazines
• Receiving long-term-oxygen or nocturnal oxygen therapy for >12 hours a day
• Diagnosis of sleep apnea that is uncontrolled
• Participation in acute phase of pulmonary rehabilitation in prior 4 weeks
• Will enter acute phase of pulmonary rehabilitation program during study
• Unable to comply with study procedures
• Affiliated with Investigator site
• Questionable validity of consent
• Use of investigational study drug/participation in clinical study in the last 30 days or 5 half lives prior to Screening, whichever is longer

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Tiotropium Handihaler	Tiotropium Handihaler	Tiotropium 18 mcg administered via Handihaler
PT001 18 mcg	Inhaled PT001	Inhaled PT001 18 mcg
PT001 36 mcg	Inhaled PT001	Inhaled PT001 36 mcg
PT001 72 mcg	Inhaled PT001	Inhaled PT001 72 mcg
PT001 144 mcg	Inhaled PT001	Inhaled PT001 144 mcg
Inhaled Placebo	Inhaled Placebo	Inhaled Placebo

Primary Outcome Measures

Name	Time	Method
Peak improvement in forced expiratory volume in one second (FEV1)	Day 1	Day 1 serial FEV1 measured over 24 hours

Secondary Outcome Measures

Name	Time	Method
Peak Improvement in inspiratory capacity (IC)	Day 1	Day 1 serial IC measured over 24 hours
Time to onset of action (>10% improvement in FEV1 from baseline)	Day 1	Day 1 serial FEV1 measured over 24 hours
Time to peak FEV1	Day 1	Day 1 serial FEV1 measured over 24 hours
FEV1 area under the curve (AUC) from 0 to 24 hours	Day 1	Day 1 serial FEV1 measured over 24 hours
FEV1 AUC from 0 to 12 hours	Day 1	Day 1 serial FEV1 measured over 24 hours
Trough FEV1 at 12 and 24 hours	Day 1	Day 1 serial FEV1 measured over 24 hours

Trial Locations

Locations (6)

Pivotal Research Centers; 🇺🇸 Peoria, Arizona, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

Elite Research Institute; 🇺🇸 Miami, Florida, United States

Pulmonary and Critical Care Medicine; 🇺🇸 Omaha, Nebraska, United States

Cincinnati VAMC; 🇺🇸 Cincinnati, Ohio, United States

Spartanburg Medical Research; 🇺🇸 Spartanburg, South Carolina, United States