A Phase 2, Randomized, Double-blind, Placebo-controlled, Efficacy and Safety Study of
Inhaled JNJ-49095397 (RV568) in Subjects With Moderate to Severe Chronic Obstructive
Pulmonary Disease

1. Be 40 to 80 years of age, inclusive.;2. Has a body mass index (BMI) <=35.0 kg/m2 at Study Visit 1.;3. Have moderate (Grade II) or severe (Grade III) COPD according to the GOLD
Guidelines at Study Visit 1 as determined by a physician.;4. Have a diagnosis of chronic bronchitis (defined as sputum production on most days for
at least 12 weeks per year for at least 2 successive years) reported by the subject at
Study Visit 1.;5. Be able to meet at least 1 of the following 2 criteria:
* Have had at least 2 COPD exacerbations requiring antibiotics and/or systemic
corticosteroids in the past 2 years, OR
* Be able to spontaneously produce an adequate sputum sample at Study Visit 1 or
Study Visit 2.;6. Be a current or ex-smoker who has a smoking history of at least 10 pack-years
(10 pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for
20 years, etc.) at Study Visit 1.;7. Have a percent-predicted postBD FEV1 >=40% and <80%, and a postBD FEV1/FVC
<0.70 at Study Visit 1.;8. Have a postBD FEV1 >500 mL at Study Visit 1.;9. Have been treated with stable doses of a LABA and/or a LAMA bronchodilator alone or
in combination with ICS for at least 4 weeks prior to Study Visit 1.;10. Have COPD symptoms that required *as needed* use of a short-acting rescue medication
within the past 4 weeks at Study Visit 1.;11. Has a chest radiograph report available within 6 months prior to Study Visit 1 or a chest
radiograph performed at Study Visit 2 that does not show any abnormality suggestive of
a malignancy or current active infection.;12. Have results of the following laboratory tests from Study Visit 1 performed at the
central laboratory that are within the limits specified below. Note: the investigator may
consider the subject eligible if the previously abnormal laboratory test result is within
normal range on a repeat test in the central laboratory. Only 1 repeat testing is allowed.
* Serum ALT levels: <=1.5 x ULN
* Total bilirubin level: <=1.5 x ULN
* Hemoglobin: >=10 g/dL (International System of Units [SI]: >=100 g/L)
* Serum glucose: <250 mg/dL
* White blood cells: *3.0 x 103 cells/mm3 (SI: *3.0 x109 cells/L)
* Platelets: >=100 x 103 cells/mm3 (SI: 100 x 109 cells/L)
* Neutrophils: >=1.5 x 103 cells/mm3 (SI: 1.5 x 109 cells/L)
Except the tests specified above, if the results of other clinical laboratory tests
(including serum chemistry, hematology, and urinalysis) are outside the normal
reference ranges, the subject must be medically stable on the basis of clinical laboratory
tests performed at screening. If the results of the serum chemistry panel, hematology, or
urinalysis are outside the normal reference ranges, the subject may be included only if
the investigator judges the abnormalities or deviations from normal to be not clinically
significant or to be appropriate and reasonable for the population under study. This
determination must be promptly reported to the sponsor*s medical monitor and recorded
in the subject's source documents and initialed by the investigator.;13. Before randomization, a woman must be either:
* Not of childbearing potential; postmenopausal (>40 years of age with amenorrhea
for at least 18 months or >40 years of age with amenorrhea for at least 6 months
and a serum follicle stimulating hormone (FSH) level >40 IU/mL); or
* Permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral oophorectomy,
bilateral salpingectomy); or otherwise be incapable of pregnancy.;14. A woman must have a negative serum (*-human chorionic gonadotropin [*-hCG]) at
Study Visit 1.;15. A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control eg, either condom with
spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository during the
study and for 6 months after receiving the last dose of study drug, and all men must also
not donate sperm during the study and for 6 months after receiving the last dose of study
drug.;16. Subjects must demonstrate the ability to use the study DPI device properly at Study
Visit 1.;17. Subject must be willing and able to adhere to the prohibitions and restrictions specified
in this protocol including prohibited medications (see exclusion criterion 4 and
Section 8) throughout the study until the end of the treatment period.;18. Each subject must sign an informed consent form (ICF) indicating that he or she
understands the purpose of and procedures required for the study and are willing to
participate in the study.;19. Each subject must sign a separate informed consent form if he or she agrees to provide
optional DNA samples for research (where local regulations permit). Refusal to give
consent for the optional DNA research samples does not exclude a subject from
participation in the study.;In addition, to be randomized, subjects must meet the following additional criteria at Study
Visit 3.:
20. At Study Visit 3, have not experienced a significant worsening of COPD based on
symptoms, daily diaries, and spirometry (in the opinion of the investigator) between
Study Visit 1 and Study Visit 3.;21. Have a postBD percent-predicted FEV1 >=38% and <80% and >500 mL at Study Visit 3.;22. At Study Visit 3, have not had a COPD exacerbation requiring antibiotics and/or
systemic steroids or a change in COPD maintenance medications (except short acting
bronchodilators) during the Screening Period (Study Visit 1 to Study Visit 3 [prior to
randomization]).;23. At Study Visit 3, have not taken any disallowed therapies as noted in exclusion
criterion 4 before the planned first dose of study agent.;24. Have not had an upper or lower respiratory infection from Study Visit 1 through Study
Visit 3.;25. At Study Visit 3, have complied with all study procedures since signing of the informed
consent.;26. Have acceptable compliance with the handheld electronic device usage in the last 7 days
prior to Visit 3, which should be at least 78% (>=11 out of 14 maximal times of use in
7 days). Lack of compliance due to mechanical malfunction of the device or other
unusual, uncontrollable circumstances based upon the investigators* judgment will not
be considered as non-compliance. In such cases, the screening period may be extended
up to 7 days for subjects to demonstrate acceptable compliance (see Section 9.1.3).

1. Has another pulmonary disease (eg, asthma, clinically significant bronchiectasis, cystic
fibrosis, sarcoidosis, interstitial lung disorder, moderate or severe sleep apnea or
pulmonary hypertension) at Study Visit 1.;2. Has an active infection, including histoplasmosis or coccidioidomycosis, tuberculosis
(TB), or non-tuberculous mycobacterial infection at Study Visit 1.;3. Has experienced life-threatening COPD (eg, requiring intensive care unit [ICU]
admission, intubation, or long-term non-invasive ventilation). Short-term (less than five
days), non-invasive ventilation during a hospitalization for an acute exacerbation of
COPD is permitted, provided that non-invasive ventilation was not continued at home.;4. Has taken any of the following COPD medications within the specified time prior to
Study Visit 1:
* Oral PDE-4 inhibitors (eg, roflumilast) within 2 weeks prior to Study Visit 1.
* Oral bronchodilators (eg, albuterol) within 2 weeks prior to Study Visit 1.
* Leukotriene modifying agents (eg, montelukast, zileuton) within 2 weeks prior
to Study Visit 1.
* Prescription xanthines (eg, theophylline, aminophylline) within 2 weeks prior to
Study Visit 1.
* Oral and IV corticosteroids for any indication within 6 weeks prior to Study
Visit 1
* Intramuscular (IM) depot corticosteroids for any indication within 12 weeks
prior to Study Visit 1.
* Cytotoxic/immunosuppressant/immunomodulatory agents within 12 weeks prior
to Study Visit 1.
* Monoclonal antibodies (eg, omalizumab) within 12 weeks prior to Study Visit 1.
* Continuous antibiotic use within 4 weeks prior to Study Visit 1.;5. Has had any of the following respiratory tract conditions within the specified time
interval:
* COPD exacerbation that required systemic corticosteroids and/or antibiotics or
required hospitalization within 6 weeks prior to Study Visit 1, or
* Upper or lower respiratory tract infection (including common cold, sinusitis,
pneumonia) within 6 weeks prior to Study Visit 1.;6. Has COPD related to α-1 antitrypsin deficiency according to medical history at Study
Visit 1.;7. Is participating in the active phase of a supervised pulmonary rehabilitation program at
Study Visit 1.;8. Has right heart failure or an oxygen saturation (SpO2, as measured by pulse oximetry)
less than 90% at rest on room air at Study Visit 1 or requires oxygen therapy on a daily
basis (>12 hours/day) for chronic hypoxemia at Study Visit 1.;9. Has had a lung lobectomy, lung cancer surgery, surgical or nonsurgical lung volume
reduction, or a lung transplant.;10. Has a clinically significant ECG abnormality at Study Visit 1 (eg, prolongation of the
QTc interval >=450 msec [either QTcB or QTcF, males or females], a history of risk
factors for Torsade de Pointes such as persistent hypokalemia, or family history of long
QT syndrome; or a history of second- or third-degree heart block).;11. Has had major surgery (eg, requiring general anesthesia) within 6 weeks before
Study Visit 1, or will not have fully recovered from surgery, or has surgery planned
during the time the subject is expected to participate in the study.
Note: subjects with planned surgical procedures to be conducted under local anesthesia
may participate.;12. Has a transplanted organ (with the exception of a corneal transplant performed more
than 3 months prior to Study Visit 1).;13. Has donated blood or has had a blood loss of more than 400 mL within 4 weeks prior to
Study Visit 1 or plans to donate blood during the study.;14. Has a recent history (within 12 months prior to Study Visit 1) of uncontrolled, chronic
disease including, but not limited to, cardiovascular, endocrine, neurological, hepatic,
gastrointestinal, renal, hematological, urological, immunological, psychiatric, metabolic
disturbances, or ophthalmic diseases that the investigator believes are clinically
significant. In case of doubt, the investigator should discuss with the medical monitor.;15. Has any condition that, in the opinion of the investigator, would make participation in
the study not be in the best interest (eg, compromise the well-being) of the subject or
that could prevent, limit, or confound the protocol-specified assessments.;16. Has positive serology to human immunodeficiency virus (HIV)-1 or HIV-2, hepatitis B
virus , or hepatitis C virus (HCV) at Study Visit 1.;17. Has any history of malignancy at Study Visit 1 with the exceptions of:
* basal cell carcinoma or squamous cell carcinoma in situ of the skin that has been
treated with no evidence of recurrence within 6 months prior to Study Visit 1, or
* squamous cell carcinoma (not in situ) or cervical carcinoma in situ that has been
treated with no evidence of recurrence within 5 years prior to Study Visit 1.;18. Has known allergies, hypersensitivity, or intolerance to JNJ-49095397 (RV568) or its
excipients (refer to the latest version of the Investigator's Brochure and Addenda for
JNJ-49095397.;19. Has previously received JNJ-49095397 (RV568).;20. Has received an investigational drug (or investigational vaccines) or used an invasive
investigational medical device within 5 half-lives (or 3 months if the half-life is
unknown) before the planned first dose of study drug, plans to enroll, or is currently
enrolled in an investigational study.;21. Is a woman who is breast-feeding while enrolled in this study or within 12 weeks after
the last dose of study drug.;22. Is a man who plans to father a child while enrolled in this study or within 6 months after
the last dose of study drug.;23. Has, or has had, a substance abuse (drug or alcohol) problem within the previous 3 years
at Study Visit 1.;24. Is, in the opinion of the investigator, known to be unreliable or noncompliant.;25. Is an employee of the investigator or study site, with direct involvement in the proposed
study or other studies under the direction of that investigator or study site, as well as
family members of the employees or the investigator.