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)

NCT ID: NCT01068145

Last Updated: 2015-03-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2011-03-31

Brief 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.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: DOUBLE

Study Groups

Very low dose SCH 527123

Group Type: EXPERIMENTAL

SCH 527123

Intervention Type: DRUG

Very low dose SCH 527123, once daily for 7 days

Low dose SCH 527123

Group Type: EXPERIMENTAL

SCH 527123

Intervention Type: DRUG

Low dose SCH 527123, once daily for 7 days

Medium dose SCH 527123

Group Type: EXPERIMENTAL

SCH 527123

Intervention Type: DRUG

Medium dose SCH 527123, once daily for 7 days

High dose SCH 527123

Group Type: EXPERIMENTAL

SCH 527123

Intervention Type: DRUG

High dose SCH 527123, once daily for 7 days

Placebo to match SCH 527123

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsules to match SCH 527123, once daily for 7 days

Low dose SCH 527123 (Part 2)

Group Type: EXPERIMENTAL

SCH 527123

Intervention Type: DRUG

Low dose capsule SCH 527123, once daily for 14 days

Medium dose SCH 527123 (Part 2)

Group Type: EXPERIMENTAL

SCH 527123

Intervention Type: DRUG

Medium dose capsule SCH 527123, once daily for 14 days

High dose SCH 527123 (Part 2)

Group Type: EXPERIMENTAL

SCH 527123

Intervention Type: DRUG

High dose capsule SCH 527123, once daily for 14 days

Placebo (Part 2)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsules to match SCH 527123, once daily for 14 days

Interventions

SCH 527123

Very low dose SCH 527123, once daily for 7 days

Intervention Type: DRUG

SCH 527123

Low dose SCH 527123, once daily for 7 days

Intervention Type: DRUG

SCH 527123

Medium dose SCH 527123, once daily for 7 days

Intervention Type: DRUG

SCH 527123

High dose SCH 527123, once daily for 7 days

Intervention Type: DRUG

Placebo

Placebo capsules to match SCH 527123, once daily for 7 days

Intervention Type: DRUG

SCH 527123

Low dose capsule SCH 527123, once daily for 14 days

Intervention Type: DRUG

SCH 527123

Medium dose capsule SCH 527123, once daily for 14 days

Intervention Type: DRUG

SCH 527123

High dose capsule SCH 527123, once daily for 14 days

Intervention Type: DRUG

Placebo

Placebo capsules to match SCH 527123, once daily for 14 days

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Holz O, Khalilieh S, Ludwig-Sengpiel A, Watz H, Stryszak P, Soni P, Tsai M, Sadeh J, Magnussen H. SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects. Eur Respir J. 2010 Mar;35(3):564-70. doi: 10.1183/09031936.00048509. Epub 2009 Jul 30.

Reference Type: RESULT

PMID: 19643947 (View on PubMed)

Other Identifiers

2008-006650-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P05567

Identifier Type: -

Identifier Source: org_study_id