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)

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: SCH 527123; Drug: SCH 527123; Drug: SCH 527123; Drug: SCH 527123; Drug: SCH 527123; Drug: SCH 527123; Drug: SCH 527123; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: February 11, 2010
• First Submitted That Met QC Criteria: February 11, 2010
• First Posted (Estimate): February 12, 2010

Study Record Updates

• Last Update Posted (Estimate): March 26, 2015
• Last Update Submitted That Met QC Criteria: March 25, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: P05567; 2008-006650-18 (EudraCT Number)