Two-Part Study to Evaluate the Dose Response of SCH 527123 on Sputum Neutrophilia Following Ozone Challenge in Healthy Subjects and Chronic Obstructive Pulmonary Disease (COPD) Patients (P05567 AM7)

Study Overview
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Brief Summary
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Trial to evaluate the dose response of SCH 527123 in reducing inflammation from an ozone-induced sputum neutrophilia in both healthy subjects and subjects with COPD.

Official Title
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Randomized, Double-Blind, Multiple-Dose, Placebo-Controlled, Incomplete Crossover, Two-Part Study to Evaluate the Dose Response of SCH 527123 on Sputum Neutrophilia Following Ozone Challenge in Healthy Subjects and COPD Patients

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: SCH 527123
* Drug: SCH 527123
* Drug: SCH 527123
* Drug: SCH 527123
* Drug: Placebo
* Drug: SCH 527123
* Drug: SCH 527123
* Drug: SCH 527123
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1 Subject of either sex and of any race between the age of 18 and 55 years, with a BMI (weight [kg]/height [m2]) between 19 and 32. Subject must have a FEV1 ≥ 80 % of predicted value. Subject must be nonsmoker (including cigarettes, cigars and pipes) or exsmoker who has stopped smoking for at least 6 months (smoking history ≤ 5 pack years). Subject's clinical laboratory tests (CBC, blood chemistry, urinalysis) must be within normal limits. Subjects must have a neutrophil count of >2.0 x 109/L. (also Part 2) Subject must be free of any clinically significant disease that would interfere with the study evaluations (also Part 2). Screening ECG conduction intervals must be within gender specific normal range; QTcB males ≤430 msec and females ≤450 msec (also Part 2). Vital sign measurements must be: a) oral body temperature, between 35.0°C and 37.5°C; b) systolic blood pressure, 90 to 140 mm Hg (160 mm Hg, Part 2); c) diastolic blood pressure, 45 to 90 mm Hg (100 mm Hg, Part 2); d) pulse rate, 40 to 100 bpm. Subject and partner(s) must be using an accepted method of contraception during the trial through 2 months post-treatment (also Part 2). Prior to randomization, subject must be a responder to ozone (also Part 2). Part 2 Subject with a diagnosis of COPD for at least 1 year and FEV1 ≥65% of predicted value post bronchodilation (measurement 30 minutes after 400 mcg salbutamol administration) and FEV1/FVC of <70%. Subject of either sex and of any race between the age of 40 and 65 years, with a BMI between 19 and 32. Subject must be active or exsmoker (cigarettes, cigars and/or pipes). Subject must have a normal exercise stress test (no clinically significant ECG findings). Exclusion Criteria: Part 1 and Part 2 Female subject who is pregnant, intends to become pregnant (within 3 months of ending the study), or is breastfeeding. Subject with history of seasonal or perennial allergic rhinitis (ie, season for specific allergen). Subject who has an allergy or a contraindication to excipients in placebo or SCH 527123 formulations or salbutamol. Surgical or medical condition (history or presence) which might alter the ADME of the drug: a) inflammatory bowel disease, ulcers, gastrointestinal or rectal bleeding; b) major gastrointestinal tract surgery, ie, gastrectomy, gastroenterostomy, or bowel resection; c) pancreatic injury or pancreatitis; d) liver disease or injury; e) impaired renal function indicated by abnormal creatinine, urinary albumin, BUN/urea or clinical significant urinary cellular constituents (eg, cast); or f) urinary obstruction or difficulty in voiding. Subject who has any infectious disease within 4 weeks prior to drug administration. Subject who is positive for hepatitis B surface antigen, hepatitis C antibodies or HIV. Subject who has a positive screen for drugs with a high potential for abuse (Screening and/or treatment period). Subjects with a history of mental instability or who have been treated for mood disorder. Subject with a history of alcohol or drug abuse in the past 2 years. Subject who has donated blood in the past 60 days. Subject who has demonstrated allergic reactions (eg, food, drug, atopic reactions or asthmatic episodes) which may interfere with ability to participate in the trial. Subject who has previously received SCH 527123 (Part 2 only) Subject who has received any of the following treatments more recently than indicated washout period prior to Baseline: Parts 1 and 2: OTC medications (excluding paracetamol), 14 days. Part 1: prescription medications, 14 days; investigational drugs, 30 days. Part 2: vitamins and herbal supplements, 14 days; statins, 4 weeks; steroids (inhaled), 4 weeks; steroids (oral and dermal), 8 weeks; antibiotics, 6 weeks; leukotriene antagonists, 4 weeks; NSAIDS, 2 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Very low dose SCH 527123<br> | Drug: SCH 527123<br>* Very low dose SCH 527123, once daily for 7 days<br>|
| Experimental: Low dose SCH 527123<br> | Drug: SCH 527123<br>* Low dose SCH 527123, once daily for 7 days<br>|
| Experimental: Medium dose SCH 527123<br> | Drug: SCH 527123<br>* Medium dose SCH 527123, once daily for 7 days<br>|
| Experimental: High dose SCH 527123<br> | Drug: SCH 527123<br>* High dose SCH 527123, once daily for 7 days<br>|
| Placebo Comparator: Placebo to match SCH 527123<br> | Drug: Placebo<br>* Placebo capsules to match SCH 527123, once daily for 7 days<br>|
| Experimental: Low dose SCH 527123 (Part 2)<br> | Drug: SCH 527123<br>* Low dose capsule SCH 527123, once daily for 14 days<br>|
| Experimental: Medium dose SCH 527123 (Part 2)<br> | Drug: SCH 527123<br>* Medium dose capsule SCH 527123, once daily for 14 days<br>|
| Experimental: High dose SCH 527123 (Part 2)<br> | Drug: SCH 527123<br>* High dose capsule SCH 527123, once daily for 14 days<br>|
| Placebo Comparator: Placebo (Part 2)<br> | Drug: Placebo<br>* Placebo capsules to match SCH 527123, once daily for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PD/PK: Dose response of SCH 527123 on ozone-induced sputum neutrophilia in healthy subjects (Part 1) and subjects with COPD (Part 2), measured by placebo-adjusted percent change in sputum neutrophil counts and absolute sputum neutrophil counts. |  | Part 1, four treatment periods, Part 2 three treatment periods duration of the trial. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD