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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

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ClinicalTrials.gov Identifier: NCT02433834
Recruitment Status : Completed
First Posted : May 5, 2015
Results First Posted : July 2, 2017
Last Update Posted : July 2, 2017
Sponsor:
Information provided by (Responsible Party):
Pearl Therapeutics, Inc.

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

Condition or disease Intervention/treatment Phase
Asthma Drug: Glycopyrronium MDI Drug: Serevent Diskus 50 μg Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 248 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : May 27, 2015
Actual Primary Completion Date : March 26, 2016
Actual Study Completion Date : March 26, 2016


Arm Intervention/treatment
Experimental: GP MDI 28.8 μg
GP MDI (PT001) 28.8 μg
Drug: Glycopyrronium MDI
GP MDI

Experimental: GP MDI 14.4 μg
GP MDI (PT001) 14.4 μg
Drug: Glycopyrronium MDI
GP MDI

Experimental: GP MDI 7.2 μg
GP MDI (PT001) 7.2 μg
Drug: Glycopyrronium MDI
GP MDI

Experimental: GP MDI 3.6 μg per
GP MDI (PT001) 3.6 μg
Drug: Glycopyrronium MDI
GP MDI

Experimental: GP MDI 1.9 μg
GP MDI (PT001) 1.9 μg
Drug: Glycopyrronium MDI
GP MDI

Placebo Comparator: Placebo
Placebo
Drug: Placebo
Active Comparator: Serevent® Diskus® 50 μg per inhalation
Serevent® Diskus® 50 μg per inhalation
Drug: Serevent Diskus 50 μg



Primary Outcome Measures :
  1. Peak Change From Baseline in FEV1 Within 3 Hours Post-dosing on Day 15 [ Time Frame: From Day 1 to Within 3 hours post dosing on Day 15 in each of 5 treatment periods ]
    Forced Expiratory Volume in 1 second (FEV1) within 3 hours post-dosing on Day 15


Secondary Outcome Measures :
  1. Change From Baseline in Morning Pre-dose Trough FEV1 on Day 15 [ Time Frame: Day 1-Day 15 in each of 5 treatment periods ]
    Change from baseline in morning pre-dose trough FEV1 on Day 15

  2. FEV1 AUC0-3 on Day 15 [ Time Frame: Day 1-Day 15 in each of 5 treatment periods ]
    FEV1 AUC0-3 is the area under the curve for the change from baseline in FEV1 calculated using the trapezoidal rule. All observed data will be used with the trapezoidal rule to calculate AUC. To aid in interpretation, all AUC values will be normalized by dividing the AUC by the time from the first to the last non-missing value (typically 3 hours).

  3. Change From Baseline in Average Daily Pre-dose PEFR Over 14 Days [ Time Frame: Day 1-Day 15 in each of 5 treatment periods ]
    Change from baseline in average daily pre-dose peak expiratory flow rate (PEFR) over 14 days Daily pre-dose PEFR and daily post-dose PEFR will each be calculated as the average of the AM and PM measurements recorded for a given day. If either the AM or PM assessment is missing, only the single measurement will be used. Analyses of average daily pre-dose PEFR, average daily post-dose PEFR, and rescue Ventolin HFA usage will use the average of the non-missing daily values recorded in the subject diaries over each week and over the last week of treatment within each period.

  4. Change From Baseline in Average Daily Post-dose PEFR Over 14 Days [ Time Frame: Day 1-Day 15 in each of 5 treatment periods ]
    Daily pre-dose PEFR and daily post-dose PEFR will each be calculated as the average of the AM and PM measurements recorded for a given day. If either the AM or PM assessment is missing, only the single measurement will be used. Analyses of average daily pre-dose PEFR, average daily post-dose PEFR, and rescue Ventolin HFA usage will use the average of the non-missing daily values recorded in the subject diaries over each week and over the last week of treatment within each period.

  5. Change From Baseline in Average Daily Rescue Medication Use Over 14 Days [ Time Frame: Day 1-Day 15 in each of 5 treatment periods ]
    Daily pre-dose PEFR and daily post-dose PEFR will each be calculated as the average of the AM and PM measurements recorded for a given day. If either the AM or PM assessment is missing, only the single measurement will be used. Analyses of average daily pre-dose PEFR, average daily post-dose PEFR, and rescue Ventolin HFA usage will use the average of the non-missing daily values recorded in the subject diaries over each week and over the last week of treatment within each period.

  6. Change From Baseline in Asthma Control Questionnaire (ACQ-5) on Day 15 [ Time Frame: Day 1-Day 15 in each of 5 treatment periods ]
    The ACQ-5 measures 5 symptoms (woken at night by symptoms, wake in the morning with symptoms, limitation of daily activities, shortness of breath, and wheeze). The scale is 0-6, where 0=minimum and 6=maximum



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02433834


Locations
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United States, Alabama
Pearl Therapeutics Inc.
Birmingham, Alabama, United States, 35209
United States, California
Pearl Therapeutics Inc.
Anaheim, California, United States, 92801
Pearl Therapeutics Inc.
Bakersfield, California, United States, 93301
Pearl Therapeutics Inc.
Cerritos, California, United States, 90703
Pearl Therapeutics Inc.
Los Angeles, California, United States, 90017
Pearl Therapeutics Inc.
Los Angeles, California, United States, 90025
Pearl Therapeutics Inc.
Los Angeles, California, United States, 90036
Pearl Therapeutics Inc.
Los Angeles, California, United States, 90048
Pearl Therapeutics Inc.
Quartz Hill, California, United States, 90036
Pearl Therapeutics Inc.
Rancho Mirage, California, United States, 92270
Pearl Therapeutics Inc.
Rolling Hills Estates, California, United States, 90274
Pearl Therapeutics Inc.
Stockton, California, United States, 95207
United States, Colorado
Pearl Therapeutics Inc.
Colorado Springs, Colorado, United States, 80907
United States, Florida
Pearl Therapeutics Inc.
Kissimmee, Florida, United States, 34744
Pearl Therapeutics Inc.
Miami, Florida, United States, 33126
Pearl Therapeutics Inc.
Miami, Florida, United States, 33186
Pearl Therapeutics Inc.
Ormond Beach, Florida, United States, 32174
United States, Illinois
Pearl Therapeutics Inc.
Evanston, Illinois, United States, 60201
United States, Iowa
Pearl Therapeutics Inc.
Iowa City, Iowa, United States, 52240
United States, Massachusetts
Pearl Therapeutics Inc.
Fall River, Massachusetts, United States, 02720
Pearl Therapeutics Inc.
North Dartmouth, Massachusetts, United States, 02747
United States, Missouri
Pearl Therapeutics Inc.
Saint Louis, Missouri, United States, 63141
United States, Nebraska
Pearl Therapeutics Inc.
Omaha, Nebraska, United States, 68114
United States, New Jersey
Pearl Therapeutics Inc.
Skillman, New Jersey, United States, 08558
Pearl Therapeutics Inc.
Verona, New Jersey, United States, 07044
United States, North Carolina
Pearl Therapeutics Inc.
Asheville, North Carolina, United States, 28801
Pearl Therapeutics Inc.
Cornelius, North Carolina, United States, 28031
Pearl Therapeutics Inc.
Gastonia, North Carolina, United States, 28054
Pearl Therapeutics Inc.
Monroe, North Carolina, United States, 28112
Pearl Therapeutics Inc.
Raleigh, North Carolina, United States, 28054
Pearl Therapeutics Inc.
Shelby, North Carolina, United States, 28152
United States, Ohio
Pearl Therapeutics Inc.
Grove City, Ohio, United States, 43123
Pearl Therapeutics Inc.
Middleburg Heights, Ohio, United States, 44130
United States, Oregon
Pearl Therapeutics Inc.
Lake Oswego, Oregon, United States, 97035
Pearl Therapeutics Inc.
Medford, Oregon, United States, 97504
United States, South Carolina
Pearl Therapeutics Inc.
Columbia, South Carolina, United States, 29201
United States, Texas
Pearl Therapeutics Inc.
Dallas, Texas, United States, 75254
Pearl Therapeutics Inc.
El Paso, Texas, United States, 79903
Pearl Therapeutics Inc.
Killeen, Texas, United States, 76543
Pearl Therapeutics Inc.
McKinney, Texas, United States, 75070
Pearl Therapeutics Inc.
New Braunfels, Texas, United States, 78130
Pearl Therapeutics Inc.
San Antonio, Texas, United States, 78229
Pearl Therapeutics Inc.
Waco, Texas, United States, 76712
Sponsors and Collaborators
Pearl Therapeutics, Inc.
Investigators
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Study Director: Shahid Siddiqui Pearl Therapeutics, Inc.
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Responsible Party: Pearl Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02433834    
Other Study ID Numbers: PT001101-00
First Posted: May 5, 2015    Key Record Dates
Results First Posted: July 2, 2017
Last Update Posted: July 2, 2017
Last Verified: May 2017
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Salmeterol Xinafoate
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action