Patients With Moderate-to-severe COPD With Destroyed Lung by Tuberculosis
Conditions
Brief summary
This clinical study will assess efficacy and safety of indacaterol (150㎍ o.d.) in patients with Chronic Obstructive Pulmonary Disease (COPD) with destroyed lung by tuberculosis.
Detailed description
There are few clinical studies in patients with COPD with destroyed lung by tuberculosis because tuberculosis patients are usually excluded from (phase II or III) clinical trials for drug registration although they are not prohibited from prescription of COPD drugs. This clinical study will assess efficacy and safety of indacaterol (150㎍ o.d.) in patients with COPD with destroyed lung by tuberculosis.
Interventions
DRUGIndacaterol
Indacaterol 150µg once daily oral inhalation
DRUGControl
Placebo once daily oral inhalation
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female adults aged ≥ 19 years in international age * Patients with a diagnosis of moderate-to-severe COPD as classified by the GOLD guidelines (2009) * Patients with at least one finding of destructed pulmonary parenchyma in the chest X-ray and the sum of all legion volumes equivalent to over 1/3 of one lung * Patients with a history of tuberculosis and no change in the chest imaging test over the past one year * Patients who can voluntarily sign an Informed Consent Form prior to initiation of any study-related procedure
Exclusion criteria
* Pregnant or nursing (lactating) women * Women of childbearing potential not willing to use effective contraception. However, those who have a negative pregnancy test and agree to use effective contraception can participate. Effective contraception does not include periodical abstinence (e.g. basal body temperature, menstrual cycle contraceptive method, etc) but means use of contraception which must include one of barrier contraceptive methods. e.g.) condom (barrier contraceptive method), diaphragms (barrier contraceptive method), oral contraceptives, intrauterine device, Depo injection, etc. * Patients who have been admitted to hospital for COPD worsening within 6 weeks prior to visit 1 * Patients with a history of respiratory infection within 6 weeks prior to visit 1 * Patients requiring long-term oxygen therapy (\>15 hours/1 day) for chronic hypoxemia (it is allowed to use up to a total of 10 out of 24 hours on a PRN basis) * Patients with a history of asthma * Unstable ischaemic heart disease, arrhythmia (except for stable ventricular fibrillation) and uncontrolled hypertension * Patients with a history of long QT syndrome or whose QTc interval measured at Visit 2 is prolonged: \>450 ms (males) or \>470 ms (females) * Uncontrolled hypothyroidism and hyperthyroidism * Hypokalemia: plasma potassium level \< 3.0 mEq/L * Patients with creatinine level ≥2 the upper limit of normal * Patients with AST/ALT level ≥2 the upper limit of normal * Patients with lung cancer or a history of lung cancer * Patients with active cancer or a history of cancer with less than 5 years disease-free survival (whether or not there is evidence of local recurrence or metastases; localized basal cell carcinoma of the skin without metastases is acceptable). * Patients with a history of hypersensitivity to any of the study drugs or to drugs with similar chemical structures including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof. * Patients who have had live attenuated vaccinations within 30 days prior to Visit 1 * Patients who have had treatment with investigational drugs, within 30 days or 5 half-lives prior to Visit 1, whichever is longer. * Patients unable to successfully use a dry powder inhaler device, metered dose inhaler or perform spirometry measurements * Other cases which are considered ineligible for this clinical study by the principal investigator and subinvestigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in One Second Change | 8 week | Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| St. George Respiratory Questionnaire for COPD (SGRQ-C) Change After 8 Weeks of Treatment | 8 week | The SGRQ-C contains 14 questions divided into two components. Part 1 produces Symptoms scores and Part 2 Activity and Impacts scores. 14 questions which are divided in three domains: symptom (question 1-7), activity (question 9, 12) and impact (question 8, 10, 11, 13 and 14). The total score is 0 to 100 with a higher score indicating greater impairment of health status. Mixed model used baseline SGRQ, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates. |
| Change From Baseline in Transition Dyspnea Index (TDI) After 8 Weeks of Treatment | 8 week | TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9 with a negative score indicating a deterioration from baseline. A 1 unit difference in the TDI focal score is clinically significant. Mixed model used baseline dyspnoea index, FEV1 prior to and 10-15 minutes post inhalation of albuterol, and FEV1 prior to 1 hour post inhalation of ipratropium as covariates. |
| Incidence of COPD Exacerbation | 8 week | Number of COPD exacerbation during 8-week treatment. COPD exacerbations are defined as a new onset or worsening of at least one respiratory symptom (i.e. dyspnea, cough, sputum purulence or volume, or wheeze) present for at least 3 consecutive days, documented change or increase in COPD-related treatment due to worsening symptoms or documented COPD-related hospitalizations or emergency room visits. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol Indacaterol 150 µg once daily | 68 |
| Placebo Placebo once daily | 68 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Consent Withdrawal | 1 | 5 |
| Overall Study | major protocol deviation | 4 | 3 |
Baseline characteristics
| Characteristic | Indacaterol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.96 Years STANDARD_DEVIATION 10.9 | 64.62 Years STANDARD_DEVIATION 9.2 | 64.29 Years STANDARD_DEVIATION 10.06 |
| Sex: Female, Male Female | 23 Participants | 28 Participants | 51 Participants |
| Sex: Female, Male Male | 45 Participants | 40 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 68 | 13 / 68 |
| serious Total, serious adverse events | 3 / 68 | 1 / 68 |
Outcome results
Primary
Trough Forced Expiratory Volume in One Second Change
Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariate
Time frame: 8 week
Population: ITT (intent to treat) population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol | Trough Forced Expiratory Volume in One Second Change | 0.08 Liters | Standard Deviation 0.16 |
| Placebo | Trough Forced Expiratory Volume in One Second Change | -0.06 Liters | Standard Deviation 0.1 |
p-value: <0.0001ANCOVA
Secondary
Change From Baseline in Transition Dyspnea Index (TDI) After 8 Weeks of Treatment
TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9 with a negative score indicating a deterioration from baseline. A 1 unit difference in the TDI focal score is clinically significant. Mixed model used baseline dyspnoea index, FEV1 prior to and 10-15 minutes post inhalation of albuterol, and FEV1 prior to 1 hour post inhalation of ipratropium as covariates.
Time frame: 8 week
Population: ITT (intent to treat) population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol | Change From Baseline in Transition Dyspnea Index (TDI) After 8 Weeks of Treatment | 1.01 Score on a scale | Standard Deviation 2.15 |
| Placebo | Change From Baseline in Transition Dyspnea Index (TDI) After 8 Weeks of Treatment | 0.23 Score on a scale | Standard Deviation 2.38 |
Secondary
Incidence of COPD Exacerbation
Number of COPD exacerbation during 8-week treatment. COPD exacerbations are defined as a new onset or worsening of at least one respiratory symptom (i.e. dyspnea, cough, sputum purulence or volume, or wheeze) present for at least 3 consecutive days, documented change or increase in COPD-related treatment due to worsening symptoms or documented COPD-related hospitalizations or emergency room visits.
Time frame: 8 week
Population: ITT (intent to treat) population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Indacaterol | Incidence of COPD Exacerbation | 3 Participants |
| Placebo | Incidence of COPD Exacerbation | 5 Participants |
Secondary
St. George Respiratory Questionnaire for COPD (SGRQ-C) Change After 8 Weeks of Treatment
The SGRQ-C contains 14 questions divided into two components. Part 1 produces Symptoms scores and Part 2 Activity and Impacts scores. 14 questions which are divided in three domains: symptom (question 1-7), activity (question 9, 12) and impact (question 8, 10, 11, 13 and 14). The total score is 0 to 100 with a higher score indicating greater impairment of health status. Mixed model used baseline SGRQ, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.
Time frame: 8 week
Population: ITT (intent to treat) population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol | St. George Respiratory Questionnaire for COPD (SGRQ-C) Change After 8 Weeks of Treatment | -2.69 Score on a scale | Standard Deviation 13 |
| Placebo | St. George Respiratory Questionnaire for COPD (SGRQ-C) Change After 8 Weeks of Treatment | -0.33 Score on a scale | Standard Deviation 16.3 |