| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 13.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10009033 |
| E.1.2 | Term | Chronic obstructive pulmonary disease |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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| 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 |
| The primary objective is to assess the efficacy of 3 dose levels (10 mg, 30 mg, and 50 mg) of SCH 527123 compared with placebo in subjects with moderate to severe COPD, based on changes from Baseline in post-bronchodilator forced expiratory volume in one second (FEV1). |
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| E.2.2 | Secondary objectives of the trial |
| The secondary objectives are to evaluate the safety and tolerability of SCH 527123 in subjects with COPD, as well as its effect on other lung function measures, specifically exacerbations, symptoms, activity measures, health-related quality of life, and markers of inflammation. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. A subject must be >40 to ≤75 years of age, of either sex, and of any race.
2. A subject must have a diagnosis of COPD based on the American Thoracic Society/European Respiratory Society (ATS/ERS)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) current guidelines, or have had symptoms consistent with COPD for ≥2 years prior to the baseline visit (Visit 2, Day 1).
3. A subject must have clinically stable COPD, indicated by no exacerbation and no change in COPD treatment within 6 weeks before Screening and no such change or exacerbation between Screening and Randomization.
4. A subject must have a history of sputum production most days of the week within the last 3 months prior to Screening.
5. At Screening, in subjects at sites performing sputum induction, post-bronchodilator FEV1 must be ≥1000 mL.
6. At Screening, a subject’s post-bronchodilator FEV1 must be ≥30% to ≤70% of the predicted value.
7. At Screening, a subject’s ratio of post-bronchodilator FEV1 to forced vital capacity (FVC) must be ≤70%.
8. A subject must be either an ex-smoker with at least 6 months of smoking cessation, or a current smoker, and must have a smoking history of ≥10 pack-years (ie, 10 pack-year history is equal to smoking 1 pack of cigarettes per day for 10 years or 2 packs per day for 5 years).
Subjects will be counseled on the risks of smoking and available smoking cessation programs prior to enrollment.
9. If a subject had used inhaled corticosteroids (ICS) during the 6 weeks prior to Screening, the subject must have kept to a stable, low or medium daily dosage of ICS, alone or in combination with a long-acting β-agonist (LABA) or a long-acting muscarinic agonist (LAMA), within the 6 weeks prior to Screening and between Screening and Randomization, and must agree to continue at this dosage during the first 26 weeks (6 months) of the Treatment Period unless directed by the investigator. A low or medium daily ICS dosage is defined in the protocol.
10. A female subject of child-bearing potential must agree to use a medically acceptable, highly effective method of birth control (ie, failure rate ≤1% per year when used consistently and correctly) prior to Screening, and agree to continue using it while in the study (Screening and Treatment Periods) if she is heterosexually active. Medically acceptable, highly effective forms of birth control are hormonal implants, oral contraceptives, hormonal patches, medically acceptable prescribed intrauterine devices (IUDs), and monogamous relationship with a male partner who has had a vasectomy.
A female subject who is not of childbearing potential must have a medical record of being surgically sterile (eg, hysterectomy, tubal ligation), or be postmenopausal. Absence of menses for at least 1 year will indicate that a female subject is postmenopausal.
A female subject should be encouraged to continue using a highly effective method of birth control 30 days following the end of treatment.
11. A female subject of child-bearing potential who is not currently sexually active must agree to use a highly effective method of contraception should she become heterosexually active while participating in the study.
12. A heterosexually active male subject must agree to use an adequate form of contraception for the duration of the study and agree to have sexual relations only with those women using a highly effective birth control method. A highly effective method of birth control is defined as that which results in a low failure rate (ie, less than 1% per year when used consistently and correctly), such as hormonal implants, injectables, combined oral contraceptives, hormonal patches, or hormonal intrauterine devices (IUD).
13. A subject must be capable of complying with the dosing regimen and visit schedules.
14. A subject must be willing not to begin any pulmonary rehabilitation program during the first 26 weeks (6 months) of the study.
15. A subject must be willing to give written informed consent to participate in the studyA subject must be willing to give written informed consent to participate in
the study. Subjects must be willing to give written informed consent for pharmacogenomic testing. Subjects who are unwilling to sign the informed consent for pharmacogenomic testing may be included in the trial, however, pharmacogenomic samples must not be obtained. |
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| E.4 | Principal exclusion criteria |
1. Subject who has been diagnosed with asthma or other clinically relevant lung disease (other than COPD) that, in the opinion of the investigator, precludes the subject from participating in the study (eg, sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis, or lung cancer).
2.Subject with clinically significant chest X-ray or computed tomography (CT) findings (eg, mass) inconsistent with stable COPD.
3. Subject who has undergone lobectomy, pneumonectomy, lung volume reduction (including bronchoscopic lung volume reduction) or any lung surgery other than biopsy.
4. Subject who has had a respiratory tract infection within 6 weeks prior to the Screening Visit (Visit 1) and/or between Visit 1 and Visit 2 (Baseline/Randomization Visit).
5. Subject with acute, non-respiratory infection(s) at Screening should be excluded until resolution of the infection(s), as determined by the investigator. (The investigator should carefully look for signs and symptoms of any infections by taking a detailed history and physical exam.)
6. Subject with >20% and ≥200 mL improvement at Screening in post bronchodilator FEV1.
7. Subject in need of supplemental oxygen therapy for >12 hours per day.
8. Subject who is breast-feeding, pregnant, or intends to become pregnant during the study.
9. Subjects who decide to discontinue smoking before Randomization are ineligible to participate. Subjects will be counseled on the risks of smoking and available smoking cessation programs prior to enrollment. However, once enrolled, if a subject elects to discontinue smoking, or reduces cigarette consumption, he/she will be allowed to complete the study.
10. Subject who is using medication that may interfere with the effect of the study medication (including but not limited to those treatments in Table 4 in the protocol, Medications Prohibited During the Study), or who has a clinically relevant medical condition that may interfere with the study procedures or evaluation, or any condition that is determined by the principal investigator to be significant. Specific examples include (but are not limited to): any history of significant cardiac disease, unstable or severe peripheral artery disease, hematologic or neurologic disease, stroke, hepatitis, abnormal renal or hepatic function tests, severe rheumatoid arthritis, known human immunodeficiency virus (HIV) diagnosis, chronic infections, significant prolongation of corrected QT (ie, QT adjusted for heart rate by Fridericia [QTcF] or Bazett [QTcB] method) >500 msec, uncontrolled or newly diagnosed (within 2 months of study entry) diabetes, insulin-dependent diabetes mellitus, or known alpha-1 antitrypsin deficiency.
11. Subject with an ANC of <3 x 10^9/L at the Visit 1 (Screening Visit).
12. Subject who has received any treatment listed in the protocol, Table 2 in the protocol, more recently than the indicated washout period prior to Screening.
13. Subject who is part of the staff personnel directly involved with this study.
14. Subject who is a family member of the investigational study staff.
15. Subject who is currently using illicit drugs or abusing alcohol. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint is defined as post-bronchodilator FEV1 during the first
26 weeks (6 months) of treatment (Period 1).
|
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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 | Yes |
| 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.8.3 |
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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 65 |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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