COPD
Conditions
Brief summary
A Randomized, Double-Blind, Parallel Group, 28-Week Chronic Dosing, Multi-Center Long-term Extension Study to Assess the Safety and Efficacy in Japanese Subjects with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) compared with Symbicort® Turbohaler®
Detailed description
This is a multicenter, randomized, double-blind, parallel group, chronic dosing, active-controlled, 28-week, safety extension of Study PT010006 to assess the safety and efficacy of BGF MDI, GFF MDI, BFF MDI, and Symbicort TBH as an active control over a 52-week period in Japanese subjects with moderate to very severe COPD who remain symptomatic on maintenance treatment with either an ICS and one or more bronchodilator(s) or two or more maintenance bronchodilators.
Interventions
DRUGBGF MDI (PT010)
Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol, BGF MDI, PT010
DRUGGFF MDI (PT003)
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol, GFF MDI, PT003
DRUGBFF MDI (PT009)
Budesonide and Formoterol Fumarate Inhalation Aerosol, BFF MDI, PT009
DRUGSymbicort® Turbohaler® Inhalation Powder
Budesonide and Formoterol Fumarate Inhalation Powder, Symbicort® Turbohaler® Inhalation Powder, Symbicort Turbohaler
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Given their signed written informed consent to participate. * Subjects must have agreed to participate and complete the lead-in Study PT010006. * 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 Visit 1, and agrees to acceptable contraceptive methods used consistently and correctly for the duration of the study. * Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS), or other local applicable guidelines. * Current or former smokers with a history of at least 10 pack-years of cigarette smoking. * Forced expiratory volume in 1 second (FEV1)/Forced vital capacity (FVC) ratio must be \<0.70 and FEV1 must be \<80% predicted normal value calculated using NHANES III reference equations (or reference norms applicable to other regions). * 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. Please refer to the study protocol for the complete inclusion criteria list.
Exclusion criteria
* 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. * 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. * Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma. * Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Visit 1 (Screening) or during the Screening Period * 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) or during the Screening Period * Immune suppression or 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. * Subjects with a diagnosis of narrow angle glaucoma, who, in the opinion of the Investigator, have not been adequately treated. * Subjects who have a history of hypersensitivity to β2-agonists, budesonide or any other corticosteroid components, glycopyrronium or other muscarinic anticholinergics, or any other component of the IMPs. Please refer to the study protocol for the complete
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | 28 Weeks | Number of participants post-baseline newly occurring or worsening PCS (potentially clinically significant) clinical chemistry values |
| Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | 28 Weeks | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs |
| Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | 28 Weeks | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values |
Countries
Japan
Participant flow
Recruitment details
This study was conducted at 75 study centers in Japan, from Aug 2016 to June 2018. This is an extension study of PT010006 and could take up to an additional 28 weeks.
Pre-assignment details
Subjects were randomized in a 2:2:1:1 scheme.
Participants by arm
| Arm | Count |
|---|---|
| BGF MDI 320/14.4/9.6 ug Budesonide Gylcopyrronium and Formoterol Fumarate Inhalation Aerosol 320/14.4/9.6 ug | 139 |
| GFF MDI 14.4/9.6 ug Glycopyrronium and Formoterol Fumarate Inhalation Aerosol 14.4/9.6 ug | 138 |
| BFF MDI 320/9.6 ug Budesonide and Formoterol Fumarate Inhalation Aerosol 320/9.6 ug | 70 |
| Symbicort TBH 400/12 ug BID Open Label Symbicort Turbuhaler 400/12 ug BID | 69 |
| Total | 416 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 12 | 4 | 6 |
| Overall Study | Lack of Efficacy | 0 | 5 | 1 | 2 |
| Overall Study | Physician Decision | 2 | 5 | 1 | 0 |
| Overall Study | Protocol Discontinuation Criteria | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 15 | 13 | 8 | 7 |
Baseline characteristics
| Characteristic | BGF MDI 320/14.4/9.6 ug | GFF MDI 14.4/9.6 ug | BFF MDI 320/9.6 ug | Symbicort TBH 400/12 ug BID | Total |
|---|---|---|---|---|---|
| Age, Continuous | 69.4 Years STANDARD_DEVIATION 7.1 | 69.0 Years STANDARD_DEVIATION 6.1 | 69.7 Years STANDARD_DEVIATION 6.1 | 70.1 Years STANDARD_DEVIATION 6.8 | 69.5 Years STANDARD_DEVIATION 6.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 139 Participants | 138 Participants | 69 Participants | 69 Participants | 415 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 139 Participants | 138 Participants | 70 Participants | 69 Participants | 416 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 9 Participants | 12 Participants | 2 Participants | 1 Participants | 24 Participants |
| Sex: Female, Male Male | 130 Participants | 126 Participants | 68 Participants | 68 Participants | 392 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 139 | 1 / 138 | 1 / 70 | 1 / 69 |
| other Total, other adverse events | 82 / 139 | 75 / 138 | 40 / 70 | 38 / 69 |
| serious Total, serious adverse events | 21 / 139 | 30 / 138 | 11 / 70 | 14 / 69 |
Outcome results
Primary
Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values
Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values
Time frame: 28 Weeks
Population: Japanese Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | Increase from baseline is >=60 msec | 1 Participants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >=530 if >=500 msec at BL and >=15 msec | 0 Participants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | Value is >500 msec and increase >=60 msec | 0 Participants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >= 500 msec and >= 15 msec change from BL | 1 Participants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >=500 if <500 msec at BL and change >=15 msec | 1 Participants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >= 500 msec and >= 15 msec change from BL | 0 Participants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | Increase from baseline is >=60 msec | 1 Participants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | Value is >500 msec and increase >=60 msec | 0 Participants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >=530 if >=500 msec at BL and >=15 msec | 0 Participants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >=500 if <500 msec at BL and change >=15 msec | 0 Participants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >= 500 msec and >= 15 msec change from BL | 0 Participants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >=500 if <500 msec at BL and change >=15 msec | 0 Participants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >=530 if >=500 msec at BL and >=15 msec | 0 Participants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | Increase from baseline is >=60 msec | 0 Participants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | Value is >500 msec and increase >=60 msec | 0 Participants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | Increase from baseline is >=60 msec | 0 Participants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >=530 if >=500 msec at BL and >=15 msec | 0 Participants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >=500 if <500 msec at BL and change >=15 msec | 0 Participants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | >= 500 msec and >= 15 msec change from BL | 0 Participants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS ECG Values | Value is >500 msec and increase >=60 msec | 0 Participants |
Primary
Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values
Number of participants post-baseline newly occurring or worsening PCS (potentially clinically significant) clinical chemistry values
Time frame: 28 Weeks
Population: Japanese Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Glucose (mmol/L) >13.9 if Baseline is ≤10.0 | 0 Count of Participants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Total Bilirubin >2 x ULN | 0 Count of Participants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Glucose (mmol/L) >16.7 if baseline is >10.0 | 0 Count of Participants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Potassium (mmol/L) >6.0 | 2 Count of Participants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | ALT >3 x ULN | 0 Count of Participants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Potassium (mmol/L) >6.0 | 0 Count of Participants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Glucose (mmol/L) >13.9 if Baseline is ≤10.0 | 1 Count of Participants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Glucose (mmol/L) >16.7 if baseline is >10.0 | 1 Count of Participants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Total Bilirubin >2 x ULN | 0 Count of Participants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | ALT >3 x ULN | 1 Count of Participants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Potassium (mmol/L) >6.0 | 0 Count of Participants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | ALT >3 x ULN | 0 Count of Participants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Total Bilirubin >2 x ULN | 0 Count of Participants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Glucose (mmol/L) >13.9 if Baseline is ≤10.0 | 1 Count of Participants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Glucose (mmol/L) >16.7 if baseline is >10.0 | 0 Count of Participants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Glucose (mmol/L) >13.9 if Baseline is ≤10.0 | 1 Count of Participants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Total Bilirubin >2 x ULN | 1 Count of Participants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | ALT >3 x ULN | 0 Count of Participants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Potassium (mmol/L) >6.0 | 0 Count of Participants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS (Potentially Clinically Significant) Clinical Chemistry Values | Glucose (mmol/L) >16.7 if baseline is >10.0 | 0 Count of Participants |
Primary
Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs
Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs
Time frame: 28 Weeks
Population: Japanese Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Systolic Blood Pressure, <=90, Decr >=20 | 4 Particpants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Systolic Blood Pressure >=180, Incr >=20 | 3 Particpants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Diastolic Blood Pressure, >=105 Incr, >=15 | 2 Particpants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Diastolic Blood Pressure, <=50, Decr >=15 | 4 Particpants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Tachycardia Event >=110, Incr >=15% | 1 Particpants |
| BGF MDI 320/14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Bradycardia Event <=50, Decr >=15% | 9 Particpants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Bradycardia Event <=50, Decr >=15% | 8 Particpants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Diastolic Blood Pressure, <=50, Decr >=15 | 3 Particpants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Systolic Blood Pressure >=180, Incr >=20 | 1 Particpants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Diastolic Blood Pressure, >=105 Incr, >=15 | 1 Particpants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Systolic Blood Pressure, <=90, Decr >=20 | 1 Particpants |
| GFF MDI 14.4/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Tachycardia Event >=110, Incr >=15% | 0 Particpants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Systolic Blood Pressure, <=90, Decr >=20 | 1 Particpants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Diastolic Blood Pressure, >=105 Incr, >=15 | 2 Particpants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Diastolic Blood Pressure, <=50, Decr >=15 | 2 Particpants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Bradycardia Event <=50, Decr >=15% | 3 Particpants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Tachycardia Event >=110, Incr >=15% | 2 Particpants |
| BFF MDI 320/9.6 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Systolic Blood Pressure >=180, Incr >=20 | 0 Particpants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Systolic Blood Pressure >=180, Incr >=20 | 0 Particpants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Tachycardia Event >=110, Incr >=15% | 0 Particpants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Bradycardia Event <=50, Decr >=15% | 2 Particpants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Diastolic Blood Pressure, <=50, Decr >=15 | 3 Particpants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Systolic Blood Pressure, <=90, Decr >=20 | 1 Particpants |
| Symbicort TBH 400/12 ug | Incidence of Post-baseline Newly Occurring or Worsening PCS Vital Signs | Diastolic Blood Pressure, >=105 Incr, >=15 | 0 Particpants |