E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009033 |
E.1.2 | Term | Chronic obstructive pulmonary disease |
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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 |
Part 1 - To assess the safety and tolerability of 3, 10, and 30 mg of SCH 527123 compared with placebo in subjects with moderate to severe COPD.
Part 2 - To assess the efficacy of 3, 10, and 30 mg of SCH 527123 compared with placebo in subjects with moderate to severe COPD, based on changes from Baseline in forced expiratory volume in one second (FEV1) and the sum of the individual symptoms of sputum production, cough, and dyspnea score. |
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E.2.2 | Secondary objectives of the trial |
Part 1 - To explore the effect of SCH 527123 compared with placebo on number and/or percent of sputum neutrophils. Sputum neutrophils, believed to play a key role in the pathophysiology of COPD, will be used as a surrogate marker for the activity of SCH 527123. A dose related decrease in sputum neutrophil counts may be regarded as proof-of-concept for SCH 527123.
Part 2 - To evaluate the safety and tolerability of SCH 527123 in subjects with COPD. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject must have a diagnosis of COPD for at least 2 years based on the American Thoracic Society (ATS) current guidelines: Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease; 1995 (http://www.thoracic.org/sections/publications/statements/pages/respiratory-disease-adults/copd1-45.html), or symptoms consistent with COPD for at least 2 years. 2. Subject must be >40 up to 75 years of age, of either sex, and of any race. 3. Subject must be current smoker with at least 10 pack-years of smoking history (eg, 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). Subject will be counseled on the risks of smoking and available smoking cessation programs prior to enrollment. Subject who elects to continue to smoke will be eligible for enrollment. Once enrolled, if a subject elects to discontinue smoking, or reduces cigarette consumption, he/she will be allowed to complete the study. 4. Subject must have a history of daily sputum production most days of the week for at least the past 3 months. 5. Post-bronchodilator FEV1 must be at least 800 mL, and at least 40% up to 70% of predicted FEV1. 6. Post-bronchodilator ratio of FEV1 to forced vital capacity (FVC) must be less than or equal to 70%. 7. A female subject of childbearing potential must be using a medically acceptable, highly effective, adequate form 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). Medically acceptable, highly effective forms of birth control are hormonal implants, oral contraceptives, medically acceptable prescribed intrauterine devices (IUDs), and monogamous relationship with a male partner who has had a vasectomy. A female subject should be encouraged to continue using a highly effective method of birth control 30 days following the end of treatment. 8. A female subject who is not currently sexually active must agree to use a medically acceptable double barrier method of contraception should she become sexually active while participating in the study. 9. A 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 women using a highly effective birth control method according to the note for guidance on nonclinical safety studies for the conduct of human clinical trials for pharmaceuticals (CPMP/ICH/286/95 mod). A highly effective method of birth control is defined as that which results in a low failure rate (ie, less that 1% per year) when used consistently and correctly, such as hormonal implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUD). 10. Female subjects who are not of childbearing potential must have a medical record of being surgically sterile ( eg, hysterectomy, tubal ligation) or be at least 1 year post menopausal. Documented absence of menses for at least 1 year will indicate that a female is postmenopausal. 11. Subject must be capable of complying with the dosing regimen and visit schedules. 12. Subject must be willing to give written informed consent to participate in the study.
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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), eg, sarcoidosis, tuberculosis, pulmonary fibrosis, bronchiectasis, or lung cancer. 2. Subject with history of previous lung surgery (eg, lobectomy, pneumonectomy, or lung volume reduction). 3. Subject who has had a lower respiratory tract infection within 4 weeks prior to the Screening Visit. 4. Subject receiving chronic antibiotic therapy. 5. Subject who has had an exacerbation of COPD within the 4 weeks prior to the Screening Visit. 6. Subject with >20% change at Screening in post-bronchodilator FEV1. 7. A subject who is breast-feeding, pregnant, or intends to become pregnant during the study. 8. Subject with clinically relevant medical condition (eg, hematologic, cardiovascular, renal, hepatic, neurologic, or metabolic). 9. Subject who has taken inhaled or systemic steroids within 4 weeks of Visit 1. 10. Subject who has received an investigational drug within the last 30 days. 11. Subject who has received any prohibited treatment listed in more recently than the indicated washout period, prior to (Screening), or who must continue to receive any prohibited treatment. 12. Subject who is part of the staff personnel directly involved with this study. 13. Subject who is a family member of the investigational study staff. 14. Subject who produced an inadequate amount of sputum at the Screening Visit (Visit 1) or is known to have difficulty producing sputum. 15. Subjects with a PBN count of <3000/μL at the Screening Visit (Visit 1). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1 - Adverse events and changes from Baseline for both absolute and percent peripheral blood neutrophil (PBN) counts.
Part 2 - Changes from Baseline in pre-bronchodilator FEV1 and changes from Baseline in the daily AM/PM SCDS, both as longitudinal averages over the 12-week treatment period.
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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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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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 | 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 |