Clinical trial NCT02433834: Chronic Dosing Cross-Over Study to Assess the Efficacy and Safety of Glycopyrronium (PT001) in Adult Subjects With Intermittent Asthma or Mild to Moderate Persistent Asthma
Official title: A Randomized, Double-Blind, Chronic-Dosing (14 Days), 5-Period, 7-Treatment, Placebo-Controlled, Incomplete Block, Cross-Over, Multicenter, Dose-ranging Study to Assess the Efficacy and Safety of PT001 Relative to Placebo Metered Dose Inhaler and Open-Label Serevent® Diskus® in Adult Subjects With Intermittent Asthma or Mild to Moderate Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-05-05
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: A Randomized, Double-Blind, Chronic Dosing (14 days), 5-Period, 7-Treatment, Placebo-Controlled, Incomplete Block, Cross-Over, Multi-center, Dose-ranging Study to Assess the Efficacy and Safety of Glycopyrronium MDI (PT001) Relative to Placebo MDI and Open-Label Serevent Diskus in Adult Subjects With Intermittent Asthma or Mild to Moderate Persistent Asthma


Eligibility criteria: Inclusion Criteria:

1. Give their signed written informed consent to participate
2. Males and females ranging in age between 18 to 70 years, inclusive, before Screening (Visit 1a)
3. A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (ie., physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or

   Child bearing potential, has a negative serum pregnancy test at Screening (Visit 1a), and agrees to 1 of the following acceptable contraceptive methods used consistently and correctly (ie., in accordance with the approved product label and the instructions of the physician for the duration of the study, from Screening \[Visit 1a\] until 14 days after Visit 12):
   * Complete abstinence from intercourse; or
   * Implants of levonorgestrel inserted for at least 1 month prior to the study drug administration, but not beyond the third successive year following insertion; or
   * Injectable progestogen administered for at least 1 month prior to study drug administration and administered for 1 month following study completion; or
   * Oral contraceptive (combined or progestogen only) administered for at least one monthly cycle prior to study drug administration; or
   * Double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository); or
   * An intrauterine device inserted by a qualified physician, with published data showing that the highest expected failure rate is less than 1% per year; or
   * Estrogenic vaginal ring; or
   * Percutaneous contraceptive patches
4. Asthma History: Have a diagnosis of intermittent asthma or mild to moderate persistent asthma, diagnosed at least 6 months prior to Screening (Visit 1a)
5. Reversibility: Diagnosis of asthma confirmed at Screening (Visits 1 and 2) with demonstration of reversibility to a bronchodilator defined as an FEV1 increase of at least 12% and at least 200 mL, 30 to 60 minutes after the inhalation of 4 puffs of salbutamol/albuterol (Ventolin HFA)
6. Pulmonary Function: Must have a pre-bronchodilator FEV1 ≥60% and ≤90% of predicted normal value at Visit 1a/b and Visit 2a/b
7. Asthma Maintenance Therapy: For those subjects receiving asthma maintenance therapy, they must be on a stable dose of ICS or non-ICS therapy (eg., LTRA) for at least 4 weeks prior to Screening (Visit 1a).
8. Results of clinical laboratory tests conducted at Screening (Visit 1a) must be acceptable to the Investigator.

Exclusion Criteria:

1. Life-Threatening Asthma: A subject must not have life-threatening asthma. Lifethreatening asthma is defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s) within the 12 months prior to Visit 1a (Screening).
2. Worsening Asthma: A subject must not have experienced a worsening of asthma that involved an emergency department visit, hospitalization, or use of oral/parenteral corticosteroids within 6 weeks of Screening (Visit 1a).
3. Seasonal or Exercise-Induced Asthma Alone: Subjects with only seasonal or exerciseinduced asthma are excluded from participation.
4. Concurrent Respiratory Disease: A subject must not have current evidence or diagnosis of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, chronic bronchitis, emphysema, COPD, or other respiratory abnormalities other than asthma.
5. Concurrent Conditions/Diseases: A subject with historical or current evidence of any clinically significant, or comorbid or uncontrolled condition or disease state that, in the opinion of the Investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the results if the condition/disease exacerbated during the study.
6. Smoking History: Current smokers or former smokers who have stopped smoking within 6 months prior to enrollment or with a \>10 pack year history of cigarettes, cigars, or pipe smoking. E-cigarettes and inhaled marijuana should be treated in the same manner as tobacco products.
7. Inhaled Anticholinergic Use: Subjects must not have used inhaled anticholinergics for at least the 2 weeks prior to Screening (Visit 1a).
8. Pregnant women or nursing mothers
9. Respiratory Tract Infection: Subjects who have had a respiratory tract infection within 6 weeks prior to Screening (Visit 1a). Subjects who develop a respiratory tract infection during the Screening Period must discontinue from the trial, but will be permitted to reenroll at a later date (at least 6 weeks after the resolution of the respiratory tract infection).
10. Uncontrolled Hypertension: Subjects who, in the opinion of the Investigator, have clinically significant uncontrolled hypertension.
11. Liver Function: Subjects with abnormal liver function tests defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin ≥1.5 times the upper limit of normal on repeat testing.
12. Renal: a. Subjects with symptomatic prostatic hypertrophy that is clinically significant in the opinion of the Investigator (if treated and asymptomatic, the subject is eligible for enrollment). Subjects with a trans-urethral resection of prostate or full resection of the prostate within 6 months prior to Visit 1a are excluded from the study.

    b. Subjects with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator. c. Subjects with a calculated creatinine clearance ≤30 mL/minute using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula \[Levey, 2009\] at Visit 1a and on repeat testing prior to Visit 3. Note: Subjects with overactive bladder syndrome treated with oral anticholinergics that have been on treatment for at least one month are allowed in the study.
13. Glaucoma: Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. Subjects with a diagnosis of glaucoma (non-angle closure), that in the opinion of the Investigator, has not been adequately treated will also be excluded. Subjects with previously diagnosed glaucoma who have intraocular pressure controlled with medication(s) are eligible. All medications approved for control of intraocular pressures are allowed including topical ophthalmic non-selective β-blockers such as betaxolol, carteolol, levobunolol, metipranolol, or timolol.
14. Cancer: Subjects who have cancer that has not been in complete remission for at least 5 years.

    Note: Subjects with squamous cell carcinoma and basal cell carcinoma of the skin that have been resected for cure are not considered exclusionary. Subjects with localized prostate cancer that in the opinion of the Investigator, has been adequately worked up, is clinically controlled, and the subject's participation in the study would not represent a safety concern, are eligible.
15. Drug Allergy: Subjects who have a history of hypersensitivity to lactose, milk proteins, or to any component of the MDI or dry powder inhaler (DPI)
16. Substance Abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2-year period prior to Screening (Visit 1a).
17. Cardiac Conditions/Disease: Subjects with documented myocardial infarction within a year from the Screening (Visit 1a) are to be excluded. Subjects with a recent history of acute coronary syndrome, or who have undergone percutaneous coronary intervention or coronary artery bypass graft within 3 months of Screening (Visit 1a) are to be excluded.

Primary outcomes:
measure: Peak Change From Baseline in FEV1 Within 3 Hours Post-dosing on Day 15
timeFrame: From Day 1 to Within 3 hours post dosing on Day 15 in each of 5 treatment periods
Secondary outcomes:
measure: Change From Baseline in Morning Pre-dose Trough FEV1 on Day 15
timeFrame: Day 1-Day 15 in each of 5 treatment periods
measure: FEV1 AUC0-3 on Day 15
timeFrame: Day 1-Day 15 in each of 5 treatment periods
measure: Change From Baseline in Average Daily Pre-dose PEFR Over 14 Days
timeFrame: Day 1-Day 15 in each of 5 treatment periods
measure: Change From Baseline in Average Daily Post-dose PEFR Over 14 Days
timeFrame: Day 1-Day 15 in each of 5 treatment periods
measure: Change From Baseline in Average Daily Rescue Medication Use Over 14 Days
timeFrame: Day 1-Day 15 in each of 5 treatment periods
measure: Change From Baseline in Asthma Control Questionnaire (ACQ-5) on Day 15
timeFrame: Day 1-Day 15 in each of 5 treatment periods
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Pearl Therapeutics Inc.
state: Alabama
city: Anaheim
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Bakersfield
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Cerritos
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Los Angeles
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Los Angeles
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Los Angeles
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Los Angeles
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Quartz Hill
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Rancho Mirage
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Rolling Hills Estates
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Stockton
country: United States
facility: Pearl Therapeutics Inc.
state: California
city: Colorado Springs
country: United States
facility: Pearl Therapeutics Inc.
state: Colorado
city: Kissimmee
country: United States
facility: Pearl Therapeutics Inc.
state: Florida
city: Miami
country: United States
facility: Pearl Therapeutics Inc.
state: Florida
city: Miami
country: United States
facility: Pearl Therapeutics Inc.
state: Florida
city: Ormond Beach
country: United States
facility: Pearl Therapeutics Inc.
state: Florida
city: Evanston
country: United States
facility: Pearl Therapeutics Inc.
state: Illinois
city: Iowa City
country: United States
facility: Pearl Therapeutics Inc.
state: Iowa
city: Fall River
country: United States
facility: Pearl Therapeutics Inc.
state: Massachusetts
city: North Dartmouth
country: United States
facility: Pearl Therapeutics Inc.
state: Massachusetts
city: Saint Louis
country: United States
facility: Pearl Therapeutics Inc.
state: Missouri
city: Omaha
country: United States
facility: Pearl Therapeutics Inc.
state: Nebraska
city: Skillman
country: United States
facility: Pearl Therapeutics Inc.
state: New Jersey
city: Verona
country: United States
facility: Pearl Therapeutics Inc.
state: New Jersey
city: Asheville
country: United States
facility: Pearl Therapeutics Inc.
state: North Carolina
city: Cornelius
country: United States
facility: Pearl Therapeutics Inc.
state: North Carolina
city: Gastonia
country: United States
facility: Pearl Therapeutics Inc.
state: North Carolina
city: Monroe
country: United States
facility: Pearl Therapeutics Inc.
state: North Carolina
city: Raleigh
country: United States
facility: Pearl Therapeutics Inc.
state: North Carolina
city: Shelby
country: United States
facility: Pearl Therapeutics Inc.
state: North Carolina
city: Grove City
country: United States
facility: Pearl Therapeutics Inc.
state: Ohio
city: Middleburg Heights
country: United States
facility: Pearl Therapeutics Inc.
state: Ohio
city: Lake Oswego
country: United States
facility: Pearl Therapeutics Inc.
state: Oregon
city: Medford
country: United States
facility: Pearl Therapeutics Inc.
state: Oregon
city: Columbia
country: United States
facility: Pearl Therapeutics Inc.
state: South Carolina
city: Dallas
country: United States
facility: Pearl Therapeutics Inc.
state: Texas
city: El Paso
country: United States
facility: Pearl Therapeutics Inc.
state: Texas
city: Killeen
country: United States
facility: Pearl Therapeutics Inc.
state: Texas
city: McKinney
country: United States
facility: Pearl Therapeutics Inc.
state: Texas
city: New Braunfels
country: United States
facility: Pearl Therapeutics Inc.
state: Texas
city: San Antonio
country: United States
facility: Pearl Therapeutics Inc.
state: Texas
city: Waco
country: United States
facility: Pearl Therapeutics Inc.
state: Texas
Study officials:
affiliation: Pearl Therapeutics, Inc.
name: Shahid Siddiqui
role: STUDY_DIRECTOR
References: