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)
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Navarixin 1 mg; Navarixin 10 mg; Placebo to match navarixin; Rescue medication
Intervention description: Navarixin 1 mg capsules; Navarixin 10 mg capsules; Placebo to navarixin capsules; Salbutamol/albuterol - 2 puffs of salbutamol/albuterol approximately every 4 hours as needed for dyspnea relief
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 99.0
Sex: All
Minimum age: 41 Years
Maximum age: 75 Years
Healthy volunteers: No

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.