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)

Conditions: Chronic Obstructive Pulmonary Disease

Summary: 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.


Eligibility criteria:
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.

Keywords: copd