Clinical trial NCT00441701: Study to Evaluate the Safety and Dose-Range of Navarixin (SCH 527123, MK-7123) in Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (MK-7123-012)
Official title: Safety and Dose-Ranging Study of the Effects of SCH 527123 in Subjects With Moderate to Severe COPD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-03-01
Enrollment: 99
Sex: ALL
Minimum age (years): 41
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a two-part study conducted at multiple centers, of navarixin (SCH 527123, MK-7123) in participants with moderate to severe chronic obstructive pulmonary disease (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. Treatment initiation for each cohort was staggered by 4 weeks to allow for safety assessment prior to use of higher doses of navarixin. 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.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of COPD based on the American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria.
* \>40 to \<=75 years of age, of either sex, and of any race.
* 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). Participant will be counseled on the risks of smoking and available smoking cessation programs prior to enrollment. Participant who elects to continue to smoke will be eligible for enrollment. Once enrolled, if a participant elects to discontinue smoking, or reduces cigarette consumption, he/she will be allowed to complete the study.
* 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%.
* Female participants 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.

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

* Female participant 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.
* Male participant 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 IUDs.

* Female participant 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.
* Capable of complying with the dosing regimen and visit schedules.
* Willing to give written informed consent to participate in the study.

Exclusion Criteria:

* Diagnosed with asthma or other clinically relevant lung disease (other than COPD), eg, sarcoidosis, tuberculosis, pulmonary fibrosis, bronchiectasis, or lung cancer.
* History of previous lung surgery (eg, lobectomy, pneumonectomy, or lung volume reduction).
* Lower respiratory tract infection within 4 weeks prior to the Screening Visit.
* Receiving chronic antibiotic therapy.
* Exacerbation of COPD within the 4 weeks prior to the Screening Visit.
* \>20% change at Screening in post-bronchodilator FEV1.
* Female participant who is breast-feeding, pregnant, or intends to become pregnant during the study.
* Clinically relevant medical conditions (eg, hematologic, cardiovascular, renal, hepatic, neurologic, or metabolic).
* Taken inhaled or systemic steroids within 4 weeks of Screening Visit (Visit 1).
* Received an investigational drug within the last 30 days.
* Produced an inadequate amount of sputum at the Screening Visit (Visit 1) or is known to have difficulty producing sputum.
* PBN count of \<3000 cells/microliters at Screening Visit (Visit 1).
* Part of the staff personnel directly involved with this study.
* Family member of the investigational study staff.
* Received any study prohibited medication more recently than the indicated washout period, prior to (Screening), or who must continue to receive any prohibited treatment.

Primary outcomes:
measure: Part 1: Number of Participants Who Experience at Least One Adverse Event (AE)
timeFrame: Up to 12 weeks
measure: Part 1: Number of Participants Who Discontinue Study Drug Due to an AE
timeFrame: Up to 12 weeks
measure: Part 1: Change From Baseline in Absolute Peripheral Blood Neutrophil (PBN) Count
timeFrame: Baseline and Week 12
measure: Part 2: Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline and the Average over 12 weeks
measure: Part 2: Change From Baseline in Daily Morning/Nighttime Sputum Production, Cough, and Dyspnea (SCDS) Score
timeFrame: Baseline and the Average over 12 weeks
Secondary outcomes:
measure: Part 1: Change From Baseline in Percent PBN Count
timeFrame: Baseline and Week 12
measure: Part 1: Change From Baseline in Sputum Absolute Neutrophil Count (Induced Sputum)
timeFrame: Baseline and Week 12
measure: Part 1: Change From Baseline in Sputum Percent Neutrophil Count (Induced Sputum)
timeFrame: Baseline and Week 12
measure: Part 2: Change From Baseline in Post-Bronchodilator FEV1
timeFrame: Baseline and the Average over 12 weeks
measure: Part 2: Change From Baseline in Forced Expiratory Flow During Middle Half of Forced Vital Capacity (FVC) (FEF25%-75%)
timeFrame: Baseline and Week 12
measure: Part 2: Change From Baseline in FVC
timeFrame: Baseline and Week 12
measure: Part 2: Change From Baseline in Functional Residual Capacity (FRC)
timeFrame: Baseline and Week 12
measure: Part 2: Number of Participants Who Experience a COPD Exacerbation
timeFrame: Up to Week 12
measure: Part 2: Change From Baseline in Peak Expiratory Flow (PEF)
timeFrame: Baseline and Week 12
measure: Part 2: Change From Baseline in Induced Sputum Absolute Neutrophil Count
timeFrame: Baseline and Week 12
measure: Part 2: Change From Baseline in Induced Sputum Percent Neutrophil Count
timeFrame: Baseline and Week 12
measure: Part 2: Change From Baseline in Individual Symptom Scores
timeFrame: Baseline and Week 12
measure: Part 2: Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Individual/Total Domains
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: