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)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 2

Conditions: Chronic Obstructive Pulmonary Disease

Treatments: Drug: Navarixin 1 mg; Drug: Rescue medication; Drug: Navarixin 10 mg; Drug: Placebo to match navarixin

Study type: Interventional

Funder types: Industry

Identifiers

NCT00441701

2005-004287-23 (EudraCT Number)

P04592 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 99 patients

Sex: All

Ages: 41 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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99 participants in 10 patient groups, including a placebo group

Part 1: Navarixin 3 mg

Experimental group

Description:

Cohort 1: Participants receive navarixin 3 mg (three 1 mg capsules) once daily (QD) for up to 12 weeks

Treatment:

Drug: Navarixin 1 mg

Drug: Rescue medication

Part 1: Placebo to navarixin 3 mg

Placebo Comparator group

Description:

Cohort 1: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks

Treatment:

Drug: Placebo to match navarixin

Drug: Rescue medication

Part 1: Navarixin 10 mg

Experimental group

Description:

Cohort 2: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks

Treatment:

Drug: Navarixin 10 mg

Drug: Placebo to match navarixin

Drug: Rescue medication

Part 1: Placebo to navarixin 10 mg

Placebo Comparator group

Description:

Cohort 2: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks

Treatment:

Drug: Placebo to match navarixin

Drug: Rescue medication

Part 1: Navarixin 30 mg

Experimental group

Description:

Cohort 3: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks

Treatment:

Drug: Navarixin 10 mg

Drug: Rescue medication

Part 1: Placebo to navarixin 30 mg

Placebo Comparator group

Description:

Cohort 3: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks

Treatment:

Drug: Placebo to match navarixin

Drug: Rescue medication

Part 2: Navarixin 3 mg

Experimental group

Description:

Cohort 4: Participants receive navarixin 3 mg (three 1 mg capsules) QD for up to 12 weeks

Treatment:

Drug: Navarixin 1 mg

Drug: Rescue medication

Part 2: Navarixin 10 mg

Experimental group

Description:

Cohort 4: Participants receive navarixin 10 mg (one 10 mg capsule and two placebo capsules) QD for up to 12 weeks

Treatment:

Drug: Navarixin 10 mg

Drug: Placebo to match navarixin

Drug: Rescue medication

Part 2: Navarixin 30 mg

Experimental group

Description:

Cohort 4: Participants receive navarixin 30 mg (three 10 mg capsules) QD for up to 12 weeks

Treatment:

Drug: Navarixin 10 mg

Drug: Rescue medication

Part 2: Placebo to navarixin

Placebo Comparator group

Description:

Cohort 4: Participants receive placebo to navarixin (three capsules) QD for up to 12 weeks

Treatment:

Drug: Placebo to match navarixin

Drug: Rescue medication