E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe chronic obstructive pulmonary disease. |
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E.1.1.1 | Medical condition in easily understood language |
Chronic obstructive pulmonary disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the safety and tolerability of 12 week treatment with RBx 10017609 (200 mg BID) in subjects with moderate to severe COPD. |
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E.2.2 | Secondary objectives of the trial |
• To assess the efficacy of 12 week treatment with RBx 10017609 (200 mg BID) with respect to change in the following parameters as compared to placebo in subjects with moderate to severe COPD:
- Sputum neutrophil count (percentage)
- FEV1
- St. George’s Respiratory Questionnaire (SGRQ)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects who have signed an informed consent consistent with ICH-GCP guidelines prior to participation in the trial at prescreening visit.
2. Male or female subjects, aged ≥40 years. Female subjects should be of non-childbearing potential [post menopausal* or those who have undergone surgical sterility (hysterectomy/bilateral tubal ligation/ bilateral oophorectomy)].
Sexually active male subjects should agree to use a medically accepted form of contraception (barrier method) or must have undergone vasectomy in the past and their partner should be either using a medically acceptable form of contraception (oral contraceptives, intrauterine contraceptive devices) or have undergone tubal ligation in the past.
3. Subjects with clinical diagnosis of COPD as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2009 and who additionally have:
- smoking history of at least 10 pack years** (current and former smokers)
- post-bronchodilator FEV1 to FVC ratio of <0.70 at screening (Visit 2).
- post-bronchodilator FEV1 of ≥30% and ≤70% of the predicted normal value at screening. Post-bronchodilator refers to within 15-30 min. of inhalation of 4x100 mcg of salbutamol delivered at mouth piece (Visit 2).
*Menopause is defined as the time when there has been no menstrual period for 12 consecutive months and no other biological or physiological cause can be identified (diagnosed on the basis of age appropriateness and history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with FSH levels greater than 40 mIU/mL at screening.
**Number of pack years = (number of cigarettes/bidis smoked per day x number of years smoked)/20.
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E.4 | Principal exclusion criteria |
1. Subjects with history of hypersensitivity to study medication / drugs of similar class or β2-agonists or any of the excipients contained in any of these formulations.
2. Subjects with Body Mass Index (BMI) of <18 or >35 kg/m2 at screening (Visit 2).
3. Pregnant* or nursing women or women of child bearing potential**.
4. Subjects having alpha-1 antitrypsin deficiency.
5. Subjects with history of asthma***.
6. Subjects with active pulmonary tuberculosis, lung or any other malignancy, bronchiectasis, cystic fibrosis or pneumonia
7. Subjects using inhaled corticosteroids (ICS) and unable to stop these during the screening/run-in period.
8. Subjects who have received treatment with oral or parenteral glucocorticosteroids within 6 weeks of screening/run-in period or depot corticosteroids within 12 weeks of screening/run-in period.
9. Subjects with history of COPD exacerbation requiring systemic glucocorticosteroids and/or antibiotics and/or hospitalization within 6 weeks of screening****(Visit 2).
10. Subjects with history of respiratory tract infection within 6 weeks of screening visit (Visit 2).
Subjects who develop a respiratory tract infection between pre-screening (Visit 1) and randomization (Visit 3) must discontinue from the trial but may be permitted to re-enroll at a later date once the inclusion/exclusion criteria have been met.
11. Subjects with hypoxemia (SpO2 < 88% on room air).
12. Subjects with significant disease(s), disorder(s) other than COPD that in the opinion of the Investigator may (i) put the subject at risk because of participation in the study or (ii) interfere with the study evaluations or (iii) cause concern regarding subject’s ability to participate in the study.
13. Subjects having arthritis/connective tissue disorder or any other joint disorder that in the opinion of the Investigator might interfere with the study evaluations
14. Subjects with history of consistent abnormal fasting blood sugar (>250 mg/dl or 14 mmol/L) or HbA1c greater than 8% at screening (Visit 2).
15. Subjects with family history of long QT syndrome.
16. Subjects with clinically significant abnormal 12-lead ECG or QTc >450 milliseconds as calculated by Fridericia formula (QTc = QT/RR0.33).
17. Subjects with history of any lung surgery (e.g., lung resection etc.).
18. Subjects with conditions which, in the opinion of the Investigator, prevent subjects from performing spirometry (e.g., hemoptysis of unknown origin, recent eye surgery etc.).
19. Subjects requiring assisted ventilation or subjects who regularly use daytime oxygen therapy for more than 1 hour per day.
20. Subjects with clinically significant abnormal haematology, biochemistry, or urinalysis; all subjects with an SGOT (AST) or SGPT (ALT) >2 times ULN or total bilirubin or serum creatinine >1.2 times ULN (Visit 2).
21. Subjects with a history of HIV or positive serology results for Hepatitis B or C in the past 3 months prior to screening (Visit 2).
22. Subjects with history of habitual alcohol consumption exceeding an average weekly intake of >21 units for males and >14 units for females***** .
23. Subjects with history of drug abuse.
24. Subjects who have received live attenuated vaccination within 4 weeks prior to screening****** (Visit 2).
25. Subjects who have received any other investigational drug within the last 3 months of screening visit (Visit 2).
26. Subjects who have previously been randomized in this study or are currently participating in another study.
27. Subjects who, in the opinion of the Investigator, are unable to perform spirometry/sputum induction procedures or complete the St. George’s Respiratory Questionnaire.
*Pregnancy is defined as a state of female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL).
** All women who are physiologically capable of becoming pregnant.
***History of asthma indicated by, but not limited to: (i) onset of respiratory symptoms suggestive of asthma prior to 40 years of age and (ii) a history of diagnosis of asthma. If the subject had an absolute eosinophil count > 600/mm3, source documentation is required to verify that the increased eosinophil count is related to a non-asthmatic condition
**** Once stable, these subjects may be reconsidered for the study.
***** 1 unit = 284 mL of beer; 25 mL of spirits or 125 mL of wine
****** The use of polysaccharide pneumococcal and hemophilus influenzae vaccines is permitted. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• To assess the safety and tolerability of 12 week treatment with RBx 10017609 (200 mg BID) in subjects with moderate to severe COPD. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To assess the efficacy of 12 week treatment with RBx 10017609 (200mg BID) with respect to change in the following parameters compared to placebo in subjects with moderate to severe COPD:
Sputum neutrophil count (percentage)
FEV1
St. George's Respiratory Questionnaire (SGRQ) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of trial at the end of Q4 2013.
This includes Query resolution, DB lock and sites close out visits. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |