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)

NCT01068145 | Terminated Phase 1

• 2 other identifiers: P055672008-006650-18
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

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

Keywords

COPD

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (9)

Very low dose SCH 527123

EXPERIMENTAL

Drug: SCH 527123

Low dose SCH 527123

EXPERIMENTAL

Drug: SCH 527123

Medium dose SCH 527123

EXPERIMENTAL

Drug: SCH 527123

High dose SCH 527123

EXPERIMENTAL

Drug: SCH 527123

Placebo to match SCH 527123

PLACEBO COMPARATOR

Drug: Placebo

Low dose SCH 527123 (Part 2)

EXPERIMENTAL

Drug: SCH 527123

Medium dose SCH 527123 (Part 2)

EXPERIMENTAL

Drug: SCH 527123

High dose SCH 527123 (Part 2)

EXPERIMENTAL

Drug: SCH 527123

Placebo (Part 2)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

SCH 527123 DRUG

Very low dose SCH 527123, once daily for 7 days

Very low dose SCH 527123

Placebo DRUG

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

Placebo to match SCH 527123

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 19643947 RESULT

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

2-hydroxy-N,N-dimethyl-3-(2-((1-(5-methylfuran-2-yl)propyl)amino)-3,4-dioxocyclobut-1-enylamino)benzamide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2010
• First Posted: February 12, 2010
• Study Start: February 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: March 26, 2015

Record last verified: 2015-03