Study to Evaluate the Safety and Dose-Range of SCH 527123 in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (Study P04592AM4)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00441701
First received: February 28, 2007
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

This is a two-part study conducted at multiple centers, in subjects with moderate to severe COPD. Part 1 of the study is a double-blind, placebo-controlled, randomized, rising-dose study consisting of four treatment groups enrolled in three cohorts. The duration of treatment, for each cohort, will be a 2-week run-in period, followed by a 12-week double-blind treatment period. Part 2 of the study will be a double-blind, placebo-controlled, randomized, parallel group study consisting of four treatment groups enrolled as one cohort. The duration of treatment will consist of a 2-week run-in period, followed by a 12-week double-blind treatment period.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Drug 1: SCH 527123
Drug: Drug 2: Placebo to match SCH 527123
Drug: Drug 3: SCH 527123
Drug: Drug 4: Placebo to match SCH 527123
Drug: Drug 5: SCH 527123
Drug: Drug 6: Placebo to match SCH 527123
Drug: Drug 7: SCH 527123
Drug: Drug 8: SCH 527123
Drug: Drug 9: SCH 527123
Drug: Drug 10: Placebo to match SCH 527123
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Safety and Dose-Ranging Study of the Effects of SCH 527123 in Subjects With Moderate to Severe COPD

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Part 1: Safety and tolerability (ie, AEs and changes from Baseline of PBN counts). [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Part 2: Primary efficacy endpoints: in pre-bronchodilator FEV1 and changes from Baseline in the daily AM/PM symptoms. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part 1: Absolute and % sputum neutrophil counts and peripheral blood neutrophils. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Part 2: Pre- & post-bronchodilator FEV1, FEF25%-75%, FVC, FRC, COPD exacerbations, exacerbations, PEF, absolute & % sputum neutrophil counts, individual symptom scores, symptoms; SGRQ individual/total domains. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: December 2006
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: SCH 527123
Cohort 1, 3 mg
Drug: Drug 1: SCH 527123
3 mg dose SCH 527123 (1 mg x3 capsules) QD for 12 weeks
Placebo Comparator: Arm 2: Placebo
Cohort 1, placebo to match 3 mg-dose of SCH 527123
Drug: Drug 2: Placebo to match SCH 527123
3 capsules QD to match SCH 527123
Experimental: Arm 3: SCH 527123
Cohort 2, 10 mg
Drug: Drug 3: SCH 527123
10 mg capsule of SCH 527123 and 2 placebo capsules QD for 12 weeks
Placebo Comparator: Arm 4: Placebo
Cohort 2, placebo to match 10 mg-dose of SCH 527123
Drug: Drug 4: Placebo to match SCH 527123
3 placebo capsules QD to match SCH 527123
Experimental: Arm 5: SCH 527123
Cohort 3, 30 mg
Drug: Drug 5: SCH 527123
30 mg dose SCH 527123 (10 mg x3 capsules) QD for 12 weeks
Placebo Comparator: Arm 6: Placebo
Cohort 3, placebo to match 30 mg-dose of SCH 527123
Drug: Drug 6: Placebo to match SCH 527123
3 placebo capsules QD to match SCH 527123
Experimental: Arm 7: SCH 527123
Cohort 4, 3 mg
Drug: Drug 7: SCH 527123
3 mg dose SCH 527123 (1 mg x3 capsules) QD for 12 weeks
Experimental: Arm 8: SCH 527123
Cohort 4, 10 mg
Drug: Drug 8: SCH 527123
10 mg capsule of SCH 527123 and 2 placebo capsules QD for 12 weeks
Experimental: Arm 9: SCH 527123
Cohort 4, 30 mg
Drug: Drug 9: SCH 527123
30 mg dose SCH 527123 (10 mg x3 capsules) QD for 12 weeks
Placebo Comparator: Arm 10: Placebo
Cohort 4, placebo to match SCH 527123
Drug: Drug 10: Placebo to match SCH 527123
3 capsules QD to match SCH 527123

  Eligibility

Ages Eligible for Study:   41 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must have a diagnosis of COPD based on the American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria.
  • Subject must be >40 to <=75 years of age, of either sex, and of any race.
  • Subject must be current smoker with at least 10 pack-years of smoking history (eg, 10 pack-year history is equal to smoking 1 pack of cigarettes per day for 10 years or 2 packs per day for 5 years). Subject will be counseled on the risks of smoking and available smoking cessation programs prior to enrollment. Subject who elects to continue to smoke will be eligible for enrollment. Once enrolled, if a subject elects to discontinue smoking, or reduces cigarette consumption, he/she will be allowed to complete the study.
  • Subject must have a history of daily sputum production for at least the past 3 months.
  • Post-bronchodilator FEV1 must be >=800 mL, and >=40% to <=70% of predicted FEV1.
  • Post-bronchodilator ratio of FEV1 to forced vital capacity (FVC) must be <=70%.
  • A female subject of childbearing potential must be using a medically acceptable, highly effective, adequate form of birth control (ie, failure rate less than 1% per year when used consistently and correctly) prior to Screening and agree to continue using it while in the study (Screening and Treatment Periods). Medically acceptable, highly effective forms of birth control are hormonal implants, oral contraceptives, medically acceptable prescribed intrauterine devices (IUDs), and monogamous relationship with a male partner who has had a vasectomy.

A female subject should be encouraged to continue using a highly effective method of birth control 30 days following the end of treatment.

  • A female subject of child-bearing potential who is not currently sexually active must agree to use a highly effective method of contraception should she become sexually active while participating in the study.
  • A male subject must agree to use an adequate form of contraception for the duration of the study and agree to have sexual relations only with women using a highly effective birth control method according to the note for guidance on non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals (CPMP/ICH/286/95 mod).

A highly effective method of birth control is defined as that which results in a low failure rate (ie, less that 1% per year) when used consistently and correctly, such as hormonal implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUD).

  • Female subject who is not of childbearing potential must have a medical record of being surgically sterile (eg, hysterectomy, tubal ligation), or be at least 1 year postmenopausal. Absence of menses for at least 1 year will indicate that a female is postmenopausal.
  • Subject must be capable of complying with the dosing regimen and visit schedules.
  • Subject must be willing to give written informed consent to participate in the study.

Exclusion Criteria:

  • Subject who has been diagnosed with asthma or other clinically relevant lung disease (other than COPD), eg, sarcoidosis, tuberculosis, pulmonary fibrosis, bronchiectasis, or lung cancer.
  • Subject with history of previous lung surgery (eg, lobectomy, pneumonectomy, or lung volume reduction).
  • Subject who has had a lower respiratory tract infection within 4 weeks prior to the Screening Visit.
  • Subject receiving chronic antibiotic therapy.
  • Subject who has had an exacerbation of COPD within the 4 weeks prior to the Screening Visit.
  • Subject with >20% change at Screening in post-bronchodilator FEV1.
  • A female subject who is breast-feeding, pregnant, or intends to become pregnant during the study.
  • Subject with clinically relevant medical conditions (eg, hematologic, cardiovascular, renal, hepatic, neurologic, or metabolic).
  • Subject who has taken inhaled or systemic steroids within 4 weeks of Visit 1.
  • Subject who has received an investigational drug within the last 30 days.
  • Subject who produced an inadequate amount of sputum at the Screening Visit (Visit 1) or is known to have difficulty producing sputum.
  • Subjects with a PBN count of <3000/micro L at the Screening Visit (Visit 1).
  • Subject who is part of the staff personnel directly involved with this study.
  • Subject who is a family member of the investigational study staff.
  • Subject who has received any study prohibited medication more recently than the indicated washout period, prior to (Screening), or who must continue to receive any prohibited treatment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00441701     History of Changes
Other Study ID Numbers: P04592, SCH 525123, EUDRACT No.: 2005-004287-23
Study First Received: February 28, 2007
Last Updated: September 24, 2013
Health Authority: Germany: Bundesinstitut fuer Arzneimittel und Medizinprodukte

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 14, 2014