Clinical Trials List
Protocol NumberPT010005
NCT Number(ClinicalTrials.gov Identfier)NCT02465567
2015-05-01 - 2019-12-31
Phase III
Terminated9
ICD-10J44.9
Chronic obstructive pulmonary disease, unspecified
ICD-10J44.1
Chronic obstructive pulmonary disease with (acute) exacerbation
ICD-9V12.6
Personal history of diseases of respiratory system
A Randomized, Double-Blind, Multi-Center, Parallel Group Study to Assess the Efficacy and Safety of PT010 Relative to PT003 and PT009 on COPD Exacerbations over a 52-Week Treatment Period in Subjects With Moderate to Very Severe COPD
-
Trial Applicant
Syneos Health
-
Sponsor
Pearl Therapeutics, Inc
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 張志豪 Division of Thoracic Medicine
- Shih-Wei Lin Division of Thoracic Medicine
- Ning-Hung Chen Division of Thoracic Medicine
- Chien-Ying Liu Division of Thoracic Medicine
- 林倡葦 Division of Thoracic Medicine
- Chih-Hung Chen Division of Thoracic Medicine
- Shih-Hong Li Division of Thoracic Medicine
- 胡漢忠 Division of Thoracic Medicine
- Chung-Chi Huang Division of Thoracic Medicine
- 李忠恕 Division of Thoracic Medicine
- Chih-Liang Wang Division of Thoracic Medicine
- Kuo-Chin Kao Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 游騰仁 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wei- Chang Huang Division of Thoracic Medicine
- Ming -Cheng Chan Division of Thoracic Medicine
- 覃俊士 Division of Thoracic Medicine
- 王振宇 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ming-Ju Tsai Division of Thoracic Medicine
- Chau-Chyun Sheu Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Yu-Chao Lin Division of Thoracic Medicine
- 廖偉志 Division of Thoracic Medicine
- 梁信杰 Division of Thoracic Medicine
- Chih-Ching Yen Division of Thoracic Medicine
- Shuo-Chueh Chen Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ping-Hung Kuo Division of Thoracic Medicine
- 許嘉林 Division of Thoracic Medicine
- 鄭之勛 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chia-Cheng Tseng Division of Thoracic Medicine
- 陳永哲 Division of Thoracic Medicine
- 吳沼漧 Division of Thoracic Medicine
- CHIN-CHOU WANG Division of Thoracic Medicine
- 黃國棟 Division of Thoracic Medicine
- 蘇茂昌 Division of Thoracic Medicine
- 趙東瀛 Division of Thoracic Medicine
- 陳友木 Division of Thoracic Medicine
- 林炯佑 Division of Thoracic Medicine
- 張晃智 Division of Thoracic Medicine
- 陳泓丞 Division of Thoracic Medicine
- 劉世豐 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
chronic obstructive pulmonary disease (COPD)
Objectives
To assess the effect of BGF MDI relative to GFF MDI and BFF MDI on the rate
of moderate or severe chronic obstructive pulmonary disease (COPD)
exacerbations
Test Drug
PT010, PT003, PT009
Active Ingredient
Budesonide、Glycopyrronium/Formoterol Fumarate(PT010)
Budesonide/Formoterol Fumarate
Glycopyrronium/Formoterol Fumarate
Budesonide/Formoterol Fumarate
Glycopyrronium/Formoterol Fumarate
Dosage Form
BGF MDI (PT010)
BGF MDI (PT010)
GFF MDI
BFF MDI
BGF MDI (PT010)
GFF MDI
BFF MDI
Dosage
160/7.2/4.8
80/7.2/4.8 μg
7.2/4.8
160/4.8
80/7.2/4.8 μg
7.2/4.8
160/4.8
Endpoints
Primary Efficacy Endpoint:
• Rate of moderate or severe COPD exacerbations
• Rate of moderate or severe COPD exacerbations
Inclution Criteria
Inclusion Criteria
Each subject must meet the following criteria to be enrolled in this study.
1. Give their signed written informed consent to participate.
2. Are at least 40 years of age and no older than 80 years at Visit 1.
3. A female is eligible to enter and participate in the study if she is of:
a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant,
including any female who is 2 years post-menopausal)
b. Childbearing potential, has a negative serum pregnancy test at Visit 1, and agrees to
one of the following acceptable contraceptive methods used consistently and correctly
as outlined below (i.e., in accordance with the approved product label and the
instructions of the physician for the duration of the study – from Visit 1 (Screening)
until 14 days after the Final Visit):
− Complete abstinence from intercourse (when it is preferred and usual lifestyle of the
patient); 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; 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.
Note: The acceptable contraceptive methods listed above are subject to locally
approved contraceptive methods.
4. COPD Diagnosis: Subjects with an established clinical history of COPD as defined by the
American Thoracic Society (ATS)/European Respiratory Society (ERS) [Celli, 2004] or by
locally applicable guidelines, e.g., JRS Guidelines [JRS, 2013] characterized by:
− Progressive airflow limitation associated with an abnormal inflammatory response of
the lungs to noxious particles or gases, primarily caused by cigarette smoking.
5. Tobacco Use: Current or former smokers with a history of at least 10 pack-years of
cigarette smoking. [Number of pack-years = (number of cigarettes per day / 20) x number
of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for
20 years represent 10 pack-years)].
6. COPD Severity: Subjects with an established clinical history of COPD and severity defined
as:
− At Visit 1, FEV1/FVC ratio must be <0.70 and FEV1 must be <65% predicted
normal value calculated using NHANES III reference equations (Or reference
norms applicable to other regions, e.g., for Japan, use JRS reference equations;
[JRS, 2013]).
− At Visit 2, post-bronchodilator FEV1/FVC ratio of <0.70 and post-bronchodilator
FEV1 must be ≥25% to <65% predicted normal value, calculated using NHANES III
reference equations (Or reference norms applicable to other regions, e.g., for
Japan, use JRS reference equations [JRS, 2013]).
− At Visit 4, the average of the -60 min and -30 min pre-dose FEV1 assessments must
be <65% predicted normal value, calculated using NHANES III reference equations
(Or reference norms applicable to other regions, e.g., for Japan, use JRS reference
equations [JRS, 2013]).
− Symptomatic (CAT ≥10) at Screening (Visit 1).
7. Required COPD Maintenance Therapy:
− All Subjects must have been on two or more inhaled maintenance therapies for the
management of their COPD for at least 6 weeks prior to Screening. Scheduled SABA
and/or scheduled SAMA are considered inhaled maintenance therapies.
8. History of Exacerbations:
− Subjects with a post-bronchodilator FEV1 <50% of predicted normal must have a
documented history of ≥ 1 moderate or severe COPD exacerbation in the 12 months
prior to Screening (Visit 1).
− Subjects with a post-bronchodilator FEV1 ≥ 50% of predicted normal must have a
documented history of ≥ 2 moderate exacerbations or a documented history of ≥1
severe COPD exacerbation in the 12 months prior to Screening (Visit 1).
Note:
Prior use of antibiotics and/or oral corticosteroids alone does not qualify as a COPD
exacerbation history unless the use was associated with treatment of worsening
symptoms of COPD (e.g. increased dyspnea, increased sputum volume, or a change
in sputum purulence (color)). Subject verbal reports are not acceptable.
- Antibiotics or corticosteroids used for the treatment of URI with no lower
respiratory symptoms do not qualify for the treatment of COPD exacerbation.
9. Subject is willing and, in the opinion of the investigator, able to adjust current COPD
therapy, as required by the protocol.
10. Screening clinical laboratory tests must be acceptable to the Investigator.
11. Screening ECG must be acceptable to the Investigator.
12. Chest x-ray or computed tomography (CT) scan of the chest/lungs within 6 months prior to
Visit 1 must be acceptable to the Investigator. Subjects who have a chest x-ray that reveals
clinically significant abnormalities not believed to be due to the presence of COPD should
not be included. A chest x-ray must be conducted if the most recent chest x-ray or CT scan
are more than 6 months old at the time of Visit 1 except in countries with restrictive
radiology assessment practice (e.g. Germany) where only subjects who have had an chest
x-ray or CT scan (thorax) performed outside of the study in the last 6 months are allowed to
be enrolled. Alternatively, in these countries, an MRI may be used instead of a CT scan or
chest x-ray as per local practice assessment.
13. Compliance: Subjects must be willing to remain at the study center as required per protocol
to complete all visit assessments.
Each subject must meet the following criteria to be enrolled in this study.
1. Give their signed written informed consent to participate.
2. Are at least 40 years of age and no older than 80 years at Visit 1.
3. A female is eligible to enter and participate in the study if she is of:
a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant,
including any female who is 2 years post-menopausal)
b. Childbearing potential, has a negative serum pregnancy test at Visit 1, and agrees to
one of the following acceptable contraceptive methods used consistently and correctly
as outlined below (i.e., in accordance with the approved product label and the
instructions of the physician for the duration of the study – from Visit 1 (Screening)
until 14 days after the Final Visit):
− Complete abstinence from intercourse (when it is preferred and usual lifestyle of the
patient); 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; 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.
Note: The acceptable contraceptive methods listed above are subject to locally
approved contraceptive methods.
4. COPD Diagnosis: Subjects with an established clinical history of COPD as defined by the
American Thoracic Society (ATS)/European Respiratory Society (ERS) [Celli, 2004] or by
locally applicable guidelines, e.g., JRS Guidelines [JRS, 2013] characterized by:
− Progressive airflow limitation associated with an abnormal inflammatory response of
the lungs to noxious particles or gases, primarily caused by cigarette smoking.
5. Tobacco Use: Current or former smokers with a history of at least 10 pack-years of
cigarette smoking. [Number of pack-years = (number of cigarettes per day / 20) x number
of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for
20 years represent 10 pack-years)].
6. COPD Severity: Subjects with an established clinical history of COPD and severity defined
as:
− At Visit 1, FEV1/FVC ratio must be <0.70 and FEV1 must be <65% predicted
normal value calculated using NHANES III reference equations (Or reference
norms applicable to other regions, e.g., for Japan, use JRS reference equations;
[JRS, 2013]).
− At Visit 2, post-bronchodilator FEV1/FVC ratio of <0.70 and post-bronchodilator
FEV1 must be ≥25% to <65% predicted normal value, calculated using NHANES III
reference equations (Or reference norms applicable to other regions, e.g., for
Japan, use JRS reference equations [JRS, 2013]).
− At Visit 4, the average of the -60 min and -30 min pre-dose FEV1 assessments must
be <65% predicted normal value, calculated using NHANES III reference equations
(Or reference norms applicable to other regions, e.g., for Japan, use JRS reference
equations [JRS, 2013]).
− Symptomatic (CAT ≥10) at Screening (Visit 1).
7. Required COPD Maintenance Therapy:
− All Subjects must have been on two or more inhaled maintenance therapies for the
management of their COPD for at least 6 weeks prior to Screening. Scheduled SABA
and/or scheduled SAMA are considered inhaled maintenance therapies.
8. History of Exacerbations:
− Subjects with a post-bronchodilator FEV1 <50% of predicted normal must have a
documented history of ≥ 1 moderate or severe COPD exacerbation in the 12 months
prior to Screening (Visit 1).
− Subjects with a post-bronchodilator FEV1 ≥ 50% of predicted normal must have a
documented history of ≥ 2 moderate exacerbations or a documented history of ≥1
severe COPD exacerbation in the 12 months prior to Screening (Visit 1).
Note:
Prior use of antibiotics and/or oral corticosteroids alone does not qualify as a COPD
exacerbation history unless the use was associated with treatment of worsening
symptoms of COPD (e.g. increased dyspnea, increased sputum volume, or a change
in sputum purulence (color)). Subject verbal reports are not acceptable.
- Antibiotics or corticosteroids used for the treatment of URI with no lower
respiratory symptoms do not qualify for the treatment of COPD exacerbation.
9. Subject is willing and, in the opinion of the investigator, able to adjust current COPD
therapy, as required by the protocol.
10. Screening clinical laboratory tests must be acceptable to the Investigator.
11. Screening ECG must be acceptable to the Investigator.
12. Chest x-ray or computed tomography (CT) scan of the chest/lungs within 6 months prior to
Visit 1 must be acceptable to the Investigator. Subjects who have a chest x-ray that reveals
clinically significant abnormalities not believed to be due to the presence of COPD should
not be included. A chest x-ray must be conducted if the most recent chest x-ray or CT scan
are more than 6 months old at the time of Visit 1 except in countries with restrictive
radiology assessment practice (e.g. Germany) where only subjects who have had an chest
x-ray or CT scan (thorax) performed outside of the study in the last 6 months are allowed to
be enrolled. Alternatively, in these countries, an MRI may be used instead of a CT scan or
chest x-ray as per local practice assessment.
13. Compliance: Subjects must be willing to remain at the study center as required per protocol
to complete all visit assessments.
Exclusion Criteria
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from the study.
1. Significant diseases or conditions other than COPD, which, in the opinion of the
Investigator, may put the subject at risk because of participation in the study or may
influence either the results of the study or the subject’s ability to participate in the study.
2. Women who are pregnant or lactating, or are planning to become pregnant during the
course of the study, or women of childbearing potential who are not using an acceptable
method of contraception.
3. Respiratory:
a. Asthma: Subjects, who in the opinion of the Investigator, have a current diagnosis
of asthma.
b. Alpha-1 Antitrypsin Deficiency: Subjects who have alpha-1 antitrypsin deficiency
as the cause of COPD.
c. Other Respiratory Disorders: Subjects who have other active pulmonary disease
such as active tuberculosis, lung cancer, significant bronchiectasis (high resolution
CT evidence of bronchiectasis that causes repeated acute exacerbations),
sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary
hypertension, or uncontrolled sleep apnea (i.e., in the opinion of the Investigator
severity of the disorder would impact the conduct of the study). Note: Allergic
rhinitis is not exclusionary.
d. Lung Volume Reduction: Subjects who have undergone lung volume reduction
surgery, lobectomy or bronchoscopic lung volume reduction (endobronchial
blockers, airway bypass, endobronchial valves, thermal vapor ablation, biological
sealants, and airway implants) within 6 months of Visit 1.
e. Hospitalization: Subjects who have been hospitalized due to poorly controlled
COPD within 6 weeks prior to Visit 1 (Screening) with less than a 4 week washout
of corticosteroids and/or antibiotics prior to Visit 1 (Screening).
f. Poorly Controlled COPD: Subjects who have poorly controlled COPD, defined
as acute worsening of COPD that requires treatment with oral corticosteroids
or antibiotics within 6 weeks prior to Visit 1 (Screening) with less than a 4 week
washout of corticosteroids and/or antibiotics prior to Visit 1 (Screening).
g. Lower Respiratory Tract Infection: Subjects who had lower respiratory tract
infections that required antibiotics within 6 weeks prior to Visit 1 (Screening) with
less than a 4 week washout of antibiotics prior to Visit 1 (Screening).
h. Other Respiratory tract infections (e.g., upper respiratory tract infection) that have
not resolved at least 7 days prior to Screening.
i. Chest x-ray (frontal and lateral) with suspicion of pneumonia or other
condition/abnormality that will require additional investigation/treatment, or put the
subject at risk because of participation in the study.
j. Risk factors for pneumonia: immune suppression (HIV) severe neurological
disorders affecting control of the upper airway or other risk factors that in the
opinion of the Investigator would put the subject at substantial risk of pneumonia.
k. Pneumonia not clinically resolved within 14 days of Visit 1.
l. Spirometry Performance
− Acceptability: Subjects who cannot perform acceptable spirometry (i.e., meet
ATS/ERS acceptability criteria)
− Repeatability: Subjects who cannot perform technically acceptable spirometry
with at least 3 acceptable flow-volume curves with 2 or more meeting ATS
repeatability criteria for FEV1 during at least 1 of the pre-bronchodilator
assessments at Visit 2 (-60 minute or -30 minute) and at the post-bronchodilator
assessment at Visit 2.
− FEV1 Baseline Stability (for PFT sub-study only): Subjects who cannot meet
protocol-specified baseline stability criteria. FEV1 baseline stability is defined
as the average of the -60 minute and -30 minute pre-dose FEV1 assessments at
Visit 4 being within ±20% or 200 mL of the mean of the pre-bronchodilator
FEV1 assessments obtained at the 2 preceding visits (average of pre-dose FEV1
assessments obtained at Visit 2 and Visit 3).
m. Oxygen: Subjects receiving long-term-oxygen therapy (LTOT) or nocturnal oxygen
therapy required for greater than 15 hours a day. Note: As needed oxygen use is
not exclusionary.
n. Subject use of any non-invasive positive pressure ventilation device. Note: Subjects
using continuous positive airway pressure or bi-level positive airway pressure for
Sleep Apnea Syndrome are allowed in the study if not used for ventilatory support.
o. Change in smoking status (i.e., start or stop smoking) or initiation of a smoking
cessation program within 6 weeks of Visit 1 and throughout the Screening Period
(Visit 1 to Visit 4).
p. Pulmonary Rehabilitation: Subjects who have participated in the acute phase of a
pulmonary rehabilitation program within 4 weeks prior to Visit 1 (Screening) or
who are scheduled to enter the acute phase of a pulmonary rehabilitation program
during the study. These subjects will be allowed to rescreen after completion of the
acute phase of pulmonary rehabilitation. Subjects who are in the maintenance phase
of a pulmonary rehabilitation program are not to be excluded.
q. Subjects who have initiated or altered the dose regimen of intranasal
corticosteroids, intranasal antihistamines, or a combination thereof within 7 days
prior to Visit 1 or during the Screening Period (Visit 1 to Visit 4).
4. Cardiac disease:
a. Subjects who have unstable ischemic heart disease, left ventricular failure, or
documented myocardial infarction within 6 months of enrollment. Subjects with a
recent history of acute coronary syndrome, or who have undergone percutaneous
coronary intervention or coronary artery bypass graft within the past 3 months are
to be excluded.
b. Subjects with congestive heart failure (CHF NYHA Class III/IV).
c. Clinically significant abnormal ECG: A clinically significant abnormal ECG is
defined as (but not limited to) any of the following:
− Clinically significant conduction abnormalities [e.g., left bundle branch block,
Wolff-Parkinson-White syndrome or evidence of second degree (Mobitz Type
II) or third degree atrioventricular block (unless pacemaker or defibrillator has
been inserted)].
− Clinically significant arrhythmias (e.g., atrial fibrillation with irregular
ventricular response, atrial flutter, ventricular tachycardia). Note: atrial
fibrillation that has been clinically stable for at least 6 months and that has been
appropriately treated with anticoagulation and controlled with a rate control
strategy (i.e., selective beta blocker, calcium channel blocker, digoxin or ablation
therapy) for at least 6 months is allowed for inclusion. In such subjects, atrial
fibrillation must be present at pre-randomization visits, with a resting ventricular
rate <100 beats per minute (bpm). At screening, the atrial fibrillation must be
confirmed by central reading.
− QT interval corrected for heart rate (using Fridericia’s formula; QTcF)
≥500 milliseconds (msec) in subjects with QRS <120 msec and QTcF ≥530 msec
in subjects with QRS ≥120 msec
− Ventricular rate <45 bpm.
− ST-T wave abnormalities deemed to be clinically significant by the Investigator.
Note: Subjects with non-specific ST-T wave abnormalities that are not deemed
clinically significant (per Investigator) are allowed.
− Any other ECG abnormalities not listed above that in the opinion of the
Investigator are clinically significant.
d. Clinically Uncontrolled Hypertension: Subjects who have clinically significant
uncontrolled hypertension.
5. Neurological:
a. Subjects with seizures requiring anticonvulsants within 12 months prior to Visit 1
(Screening). Note: Subjects treated with anticonvulsant medication for 12 months or
more with no seizure events are eligible.
b. Subjects taking selective serotonin reuptake inhibitors (SSRIs) or
serotonin-norepinephrine reuptake inhibitors (SNRIs) whose dose has not been stable
for at least four weeks prior to Visit 1 or is altered at any point during the Screening
Period (Visit 1 to Visit 4), or exceeds the maximum recommended dose.
c. Subjects who have experienced a cerebrovascular accident within 6 months prior to
Visit 1.
6. Renal:
a. Subjects with symptomatic prostatic hypertrophy that is clinically significant and not
adequately controlled with appropriate therapy in the opinion of the Investigator.
Subjects with a trans-urethral resection of prostate or full resection of the prostate
within 6 months prior to Visit 1 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 ≤50 mL/minute (≤30 mL/minute for
Japan) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
formula [Levey, 2009] at Visit 1 and on repeat testing prior to Visit 2.
Note: Subjects with overactive bladder syndrome treated with oral anticholinergics who
have been on treatment for at least 1 month are allowed in the study.
7. Endocrine:
a. Subjects, who in the opinion of the Investigator, have uncontrolled hypo- or
hyperthyroidism, hypokalemia, or hyperadrenergic state.
b. Subjects, who in the opinion of the Investigator, have uncontrolled Type I or II
diabetes.
8. Liver: Subjects with abnormal liver function tests defined as AST, ALT, or total
bilirubin ≥1.5 times upper limit of normal at Visit 1 and on repeat testing prior to Visit 2.
Note: Chronic stable hepatitis B and C is acceptable if the subject otherwise meets study
entry criteria.
9. Cancer: Subjects who have cancer that has not been in complete remission for at least five
years. Note: Subjects with squamous cell carcinoma of the skin, basal cell carcinoma of
the skin, or localized prostate cancer are eligible, if in the opinion of the Investigator, the
condition has been adequately worked up, is clinically controlled and the subject’s
participation in the study would not represent a safety concern.
10. Glaucoma: Subjects with a diagnosis of narrow angle glaucoma, which, in the opinion of
the Investigator, have not been adequately treated. All medications approved for control of
intraocular pressures are allowed including topical ophthalmic non-selective beta-blockers
(such as betaxolol, carteolol, levobunolol, metipranolol, and timolol), and prostaglandin
analogues.
11. Drug Allergy: Subjects who have a history of hypersensitivity to β2-agonists, budesonide or
any other corticosteroid components, glycopyrronium or other muscarinic anticholinergics,
or any component of the MDI or dry powder inhaler (DPI).
12. Substance Abuse: Subjects, who in the opinion of the Investigator, significantly abuse
alcohol or drugs.
13. Medication prior to spirometry: Subjects who are medically unable to withhold their shortacting bronchodilators for the 6-hour period required prior to spirometry testing at each
study visit will be ineligible to participate in the PFT sub-study.
14. Prohibited Medications: Subjects who, in the opinion of the Investigator, would be unable
to abstain from protocol-defined prohibited medications during the screening period and
treatment phases of this study (refer to Section 5.4).
15. Subjects using any herbal inhalation and nebulizer products within 2 weeks prior to Visit 1
(Screening) and do not agree to stop using them during the study drug treatment
16. Vaccinations Subjects who received a live attenuated vaccination within 7 days prior to
Visit 1 (Screening).
17. Non-compliance: Subjects unable to comply with study procedures including
non-compliance with diary completion (i.e., <70% subject completion of diary assessments
in the last 7 days preceding Visit 4).
18. Affiliations with Investigator site: Study Investigators, sub-Investigators, study
coordinators, employees of a participating Investigator or immediate family members
of the aforementioned are excluded from participation in this study.
19. Questionable Validity of Consent: Subjects with a history of psychiatric disease,
intellectual deficiency, poor motivation, substance abuse (including drug and alcohol),
or other conditions that will limit the validity of informed consent to participate in the
study.
20. Subjects using prohibited medications (refer to Table 5-1)
21. Investigational Drugs or Devices: Treatment with investigational study drug or device in
another clinical study within the last 30 days or five half-lives prior to Visit 1 (Screening),
whichever is longer.
Note: Subject participation in observational studies (i.e., studies that do not require change
to medication or an additional intervention) is not exclusionary.
22. Hand-to-Breath Coordination: Subjects who require the use of a spacer device to
compensate for poor hand-to-breath coordination with a MDI. Note: Use of a nebulizer to
deliver maintenance COPD medications is prohibited throughout the study.
23. Previous Participation: Subjects who were previously enrolled in any PT009 or PT010
study conducted or sponsored by Pearl Therapeutics, Inc.
Subjects who meet any of the following criteria will be excluded from the study.
1. Significant diseases or conditions other than COPD, which, in the opinion of the
Investigator, may put the subject at risk because of participation in the study or may
influence either the results of the study or the subject’s ability to participate in the study.
2. Women who are pregnant or lactating, or are planning to become pregnant during the
course of the study, or women of childbearing potential who are not using an acceptable
method of contraception.
3. Respiratory:
a. Asthma: Subjects, who in the opinion of the Investigator, have a current diagnosis
of asthma.
b. Alpha-1 Antitrypsin Deficiency: Subjects who have alpha-1 antitrypsin deficiency
as the cause of COPD.
c. Other Respiratory Disorders: Subjects who have other active pulmonary disease
such as active tuberculosis, lung cancer, significant bronchiectasis (high resolution
CT evidence of bronchiectasis that causes repeated acute exacerbations),
sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary
hypertension, or uncontrolled sleep apnea (i.e., in the opinion of the Investigator
severity of the disorder would impact the conduct of the study). Note: Allergic
rhinitis is not exclusionary.
d. Lung Volume Reduction: Subjects who have undergone lung volume reduction
surgery, lobectomy or bronchoscopic lung volume reduction (endobronchial
blockers, airway bypass, endobronchial valves, thermal vapor ablation, biological
sealants, and airway implants) within 6 months of Visit 1.
e. Hospitalization: Subjects who have been hospitalized due to poorly controlled
COPD within 6 weeks prior to Visit 1 (Screening) with less than a 4 week washout
of corticosteroids and/or antibiotics prior to Visit 1 (Screening).
f. Poorly Controlled COPD: Subjects who have poorly controlled COPD, defined
as acute worsening of COPD that requires treatment with oral corticosteroids
or antibiotics within 6 weeks prior to Visit 1 (Screening) with less than a 4 week
washout of corticosteroids and/or antibiotics prior to Visit 1 (Screening).
g. Lower Respiratory Tract Infection: Subjects who had lower respiratory tract
infections that required antibiotics within 6 weeks prior to Visit 1 (Screening) with
less than a 4 week washout of antibiotics prior to Visit 1 (Screening).
h. Other Respiratory tract infections (e.g., upper respiratory tract infection) that have
not resolved at least 7 days prior to Screening.
i. Chest x-ray (frontal and lateral) with suspicion of pneumonia or other
condition/abnormality that will require additional investigation/treatment, or put the
subject at risk because of participation in the study.
j. Risk factors for pneumonia: immune suppression (HIV) severe neurological
disorders affecting control of the upper airway or other risk factors that in the
opinion of the Investigator would put the subject at substantial risk of pneumonia.
k. Pneumonia not clinically resolved within 14 days of Visit 1.
l. Spirometry Performance
− Acceptability: Subjects who cannot perform acceptable spirometry (i.e., meet
ATS/ERS acceptability criteria)
− Repeatability: Subjects who cannot perform technically acceptable spirometry
with at least 3 acceptable flow-volume curves with 2 or more meeting ATS
repeatability criteria for FEV1 during at least 1 of the pre-bronchodilator
assessments at Visit 2 (-60 minute or -30 minute) and at the post-bronchodilator
assessment at Visit 2.
− FEV1 Baseline Stability (for PFT sub-study only): Subjects who cannot meet
protocol-specified baseline stability criteria. FEV1 baseline stability is defined
as the average of the -60 minute and -30 minute pre-dose FEV1 assessments at
Visit 4 being within ±20% or 200 mL of the mean of the pre-bronchodilator
FEV1 assessments obtained at the 2 preceding visits (average of pre-dose FEV1
assessments obtained at Visit 2 and Visit 3).
m. Oxygen: Subjects receiving long-term-oxygen therapy (LTOT) or nocturnal oxygen
therapy required for greater than 15 hours a day. Note: As needed oxygen use is
not exclusionary.
n. Subject use of any non-invasive positive pressure ventilation device. Note: Subjects
using continuous positive airway pressure or bi-level positive airway pressure for
Sleep Apnea Syndrome are allowed in the study if not used for ventilatory support.
o. Change in smoking status (i.e., start or stop smoking) or initiation of a smoking
cessation program within 6 weeks of Visit 1 and throughout the Screening Period
(Visit 1 to Visit 4).
p. Pulmonary Rehabilitation: Subjects who have participated in the acute phase of a
pulmonary rehabilitation program within 4 weeks prior to Visit 1 (Screening) or
who are scheduled to enter the acute phase of a pulmonary rehabilitation program
during the study. These subjects will be allowed to rescreen after completion of the
acute phase of pulmonary rehabilitation. Subjects who are in the maintenance phase
of a pulmonary rehabilitation program are not to be excluded.
q. Subjects who have initiated or altered the dose regimen of intranasal
corticosteroids, intranasal antihistamines, or a combination thereof within 7 days
prior to Visit 1 or during the Screening Period (Visit 1 to Visit 4).
4. Cardiac disease:
a. Subjects who have unstable ischemic heart disease, left ventricular failure, or
documented myocardial infarction within 6 months of enrollment. Subjects with a
recent history of acute coronary syndrome, or who have undergone percutaneous
coronary intervention or coronary artery bypass graft within the past 3 months are
to be excluded.
b. Subjects with congestive heart failure (CHF NYHA Class III/IV).
c. Clinically significant abnormal ECG: A clinically significant abnormal ECG is
defined as (but not limited to) any of the following:
− Clinically significant conduction abnormalities [e.g., left bundle branch block,
Wolff-Parkinson-White syndrome or evidence of second degree (Mobitz Type
II) or third degree atrioventricular block (unless pacemaker or defibrillator has
been inserted)].
− Clinically significant arrhythmias (e.g., atrial fibrillation with irregular
ventricular response, atrial flutter, ventricular tachycardia). Note: atrial
fibrillation that has been clinically stable for at least 6 months and that has been
appropriately treated with anticoagulation and controlled with a rate control
strategy (i.e., selective beta blocker, calcium channel blocker, digoxin or ablation
therapy) for at least 6 months is allowed for inclusion. In such subjects, atrial
fibrillation must be present at pre-randomization visits, with a resting ventricular
rate <100 beats per minute (bpm). At screening, the atrial fibrillation must be
confirmed by central reading.
− QT interval corrected for heart rate (using Fridericia’s formula; QTcF)
≥500 milliseconds (msec) in subjects with QRS <120 msec and QTcF ≥530 msec
in subjects with QRS ≥120 msec
− Ventricular rate <45 bpm.
− ST-T wave abnormalities deemed to be clinically significant by the Investigator.
Note: Subjects with non-specific ST-T wave abnormalities that are not deemed
clinically significant (per Investigator) are allowed.
− Any other ECG abnormalities not listed above that in the opinion of the
Investigator are clinically significant.
d. Clinically Uncontrolled Hypertension: Subjects who have clinically significant
uncontrolled hypertension.
5. Neurological:
a. Subjects with seizures requiring anticonvulsants within 12 months prior to Visit 1
(Screening). Note: Subjects treated with anticonvulsant medication for 12 months or
more with no seizure events are eligible.
b. Subjects taking selective serotonin reuptake inhibitors (SSRIs) or
serotonin-norepinephrine reuptake inhibitors (SNRIs) whose dose has not been stable
for at least four weeks prior to Visit 1 or is altered at any point during the Screening
Period (Visit 1 to Visit 4), or exceeds the maximum recommended dose.
c. Subjects who have experienced a cerebrovascular accident within 6 months prior to
Visit 1.
6. Renal:
a. Subjects with symptomatic prostatic hypertrophy that is clinically significant and not
adequately controlled with appropriate therapy in the opinion of the Investigator.
Subjects with a trans-urethral resection of prostate or full resection of the prostate
within 6 months prior to Visit 1 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 ≤50 mL/minute (≤30 mL/minute for
Japan) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
formula [Levey, 2009] at Visit 1 and on repeat testing prior to Visit 2.
Note: Subjects with overactive bladder syndrome treated with oral anticholinergics who
have been on treatment for at least 1 month are allowed in the study.
7. Endocrine:
a. Subjects, who in the opinion of the Investigator, have uncontrolled hypo- or
hyperthyroidism, hypokalemia, or hyperadrenergic state.
b. Subjects, who in the opinion of the Investigator, have uncontrolled Type I or II
diabetes.
8. Liver: Subjects with abnormal liver function tests defined as AST, ALT, or total
bilirubin ≥1.5 times upper limit of normal at Visit 1 and on repeat testing prior to Visit 2.
Note: Chronic stable hepatitis B and C is acceptable if the subject otherwise meets study
entry criteria.
9. Cancer: Subjects who have cancer that has not been in complete remission for at least five
years. Note: Subjects with squamous cell carcinoma of the skin, basal cell carcinoma of
the skin, or localized prostate cancer are eligible, if in the opinion of the Investigator, the
condition has been adequately worked up, is clinically controlled and the subject’s
participation in the study would not represent a safety concern.
10. Glaucoma: Subjects with a diagnosis of narrow angle glaucoma, which, in the opinion of
the Investigator, have not been adequately treated. All medications approved for control of
intraocular pressures are allowed including topical ophthalmic non-selective beta-blockers
(such as betaxolol, carteolol, levobunolol, metipranolol, and timolol), and prostaglandin
analogues.
11. Drug Allergy: Subjects who have a history of hypersensitivity to β2-agonists, budesonide or
any other corticosteroid components, glycopyrronium or other muscarinic anticholinergics,
or any component of the MDI or dry powder inhaler (DPI).
12. Substance Abuse: Subjects, who in the opinion of the Investigator, significantly abuse
alcohol or drugs.
13. Medication prior to spirometry: Subjects who are medically unable to withhold their shortacting bronchodilators for the 6-hour period required prior to spirometry testing at each
study visit will be ineligible to participate in the PFT sub-study.
14. Prohibited Medications: Subjects who, in the opinion of the Investigator, would be unable
to abstain from protocol-defined prohibited medications during the screening period and
treatment phases of this study (refer to Section 5.4).
15. Subjects using any herbal inhalation and nebulizer products within 2 weeks prior to Visit 1
(Screening) and do not agree to stop using them during the study drug treatment
16. Vaccinations Subjects who received a live attenuated vaccination within 7 days prior to
Visit 1 (Screening).
17. Non-compliance: Subjects unable to comply with study procedures including
non-compliance with diary completion (i.e., <70% subject completion of diary assessments
in the last 7 days preceding Visit 4).
18. Affiliations with Investigator site: Study Investigators, sub-Investigators, study
coordinators, employees of a participating Investigator or immediate family members
of the aforementioned are excluded from participation in this study.
19. Questionable Validity of Consent: Subjects with a history of psychiatric disease,
intellectual deficiency, poor motivation, substance abuse (including drug and alcohol),
or other conditions that will limit the validity of informed consent to participate in the
study.
20. Subjects using prohibited medications (refer to Table 5-1)
21. Investigational Drugs or Devices: Treatment with investigational study drug or device in
another clinical study within the last 30 days or five half-lives prior to Visit 1 (Screening),
whichever is longer.
Note: Subject participation in observational studies (i.e., studies that do not require change
to medication or an additional intervention) is not exclusionary.
22. Hand-to-Breath Coordination: Subjects who require the use of a spacer device to
compensate for poor hand-to-breath coordination with a MDI. Note: Use of a nebulizer to
deliver maintenance COPD medications is prohibited throughout the study.
23. Previous Participation: Subjects who were previously enrolled in any PT009 or PT010
study conducted or sponsored by Pearl Therapeutics, Inc.
The Estimated Number of Participants
-
Taiwan
80 participants
-
Global
8000 participants
