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)

Phase 1

Terminated

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: SCH 527123; Drug: Placebo

• Registration Number: NCT01068145
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-02
• Study First Submitted: 2010-02-11
• Study First Submitted QC: 2010-02-11
• Study First Posted: 2010-02-12
• Primary Completion: 2011-03
• Study Completion: 2011-03
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-25
• Last Update Posted: 2015-03-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Very low dose SCH 527123	SCH 527123	-
Placebo to match SCH 527123	Placebo	-
High dose SCH 527123 (Part 2)	SCH 527123	-
Medium dose SCH 527123	SCH 527123	-
Placebo (Part 2)	Placebo	-
Low dose SCH 527123	SCH 527123	-
High dose SCH 527123	SCH 527123	-
Low dose SCH 527123 (Part 2)	SCH 527123	-
Medium dose SCH 527123 (Part 2)	SCH 527123	-

Primary Outcome Measures

Name	Time	Method
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.