Clinical trial NCT00871182: Study to Evaluate the Safety and Efficacy of Inhaled PT001 in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official title: A Randomized, Double-blind, Single Dose, Four-period, Six-treatment, Placebo-controlled, Balanced, Incomplete Block, Cross-over, Study of Four Doses of Inhaled PT001 in Patients With Mild to Moderate COPD, Compared to Open Label Tiotropium
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
obstructive lung diseases
Tiotropium
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2009-03-30
Enrollment: 33
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Peak improvement in forced expiratory volume in one second (FEV1)
timeFrame: Day 1
Secondary outcomes:
measure: Time to onset of action (>10% improvement in FEV1 from baseline)
timeFrame: Day 1
measure: Time to peak FEV1
timeFrame: Day 1
measure: FEV1 area under the curve (AUC) from 0 to 24 hours
timeFrame: Day 1
measure: FEV1 AUC from 0 to 12 hours
timeFrame: Day 1
measure: Trough FEV1 at 12 and 24 hours
timeFrame: Day 1
measure: Peak Improvement in inspiratory capacity (IC)
timeFrame: Day 1
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Pivotal Research Centers
state: Arizona
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Miami
country: United States
facility: Elite Research Institute
state: Florida
city: Omaha
country: United States
facility: Pulmonary and Critical Care Medicine
state: Nebraska
city: Cincinnati
country: United States
facility: Cincinnati VAMC
state: Ohio
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
Study officials:
affiliation: Pearl Therapeutics, Inc.
name: Colin Reisner, M.D.
role: STUDY_DIRECTOR
References:
citation: Rennard S, Fogarty C, Reisner C, Fernandez C, Fischer T, Golden M, Rose ES, Darken P, Tardie G, Orevillo C. Randomized study of the safety, pharmacokinetics, and bronchodilatory efficacy of a proprietary glycopyrronium metered-dose inhaler in study patients with chronic obstructive pulmonary disease. BMC Pulm Med. 2014 Jul 16;14:118. doi: 10.1186/1471-2466-14-118.