A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of JNJ-42160443 as Adjunctive Therapy in Subjects With Cancer-Related Pain, Followed by an Open-Label Extension Phase

• Have a life expectancy of at least 3 months • Have a diagnosis of moderate to severe pain directly related to an active form of cancer and inadequately controlled by standard pain therapies; the primary site of pain should not be pain due to treatment of the cancer (eg, post-operative or procedural pain, chemotherapy- or radiotherapy-induced pain, or pain due to other comorbidities related to the cancer (eg, chronic postherpetic neuralgia, chemotherapy-induced neuropathy, osteoporotic fractures) • Currently receiving opioid analgesics at screening: - The baseline, around-the-clock dose should be >=60 mg of oral morphine equivalents, not including breakthrough pain medication doses - The baseline opioid dose should be given as a sustained-release formulation at a stable dose for at least 1 week before screening - A stable, baseline opioid dose is defined as a dose that does not fluctuate by more than 50% from the average dose over the 1 week before screening; the dose may fluctuate by more than 50% for up to 2 days, if medically necessary - The baseline opioid dose is expected to remain stable during the double-blind treatment phase - Not more than an average of 4 breakthrough pain medication doses per day during the 1 week before screening • If currently receiving nonopioid analgesics and adjuvant pain therapies (eg, anticonvulsants, antidepressants, NSAIDs, corticosteroids, pharmaceutical cannabinoids [eg, Marinol®, Sativex®, Cesamet*]), must be at stable doses for at least 1 week before screening and expected to remain stable during the double-blind treatment phase • Have an average daily pain intensity score of >=4 averaged over the last 3 days before randomization (Day 1), where the minimum single assessment score is >=2, and a worst pain score of >=5 averaged over the last 3 days before randomization, using an 11-point NRS, with 0=no pain and 10=pain as bad as you can imagine. Subjects must have recorded NRS pain assessments in their diary for at least 2 of the 3 days before randomization to determine eligibility for entry into the double-blind treatment phase. To be eligible to enter the open-label extension phase, the following key criterion must be met: -Must have completed the double-blind treatment phase of the study -Women of childbearing potential must have a negative urine B-hCG pregnancy test at the end of the double-blind treatment phase (Day 29) -Subjects can participate in 2 trials simultaneously during the open-label extension phase if the other investigational drug is approved in the local country and the side effect profile is well documented. Each case must be pre-approved by the J&J PRD medical monitor. Breakthrough pain medication trials will be handled on a case by case basis.

• Presence of neurologic deficits that are: - Grade 3 or higher motor or sensory deficits, graded according to the Modified Neuropathy Common Terminology Criteria for Adverse Events, or - Unstable or progressive, or - Stable for <3 months before screening, or - Caused by a potentially progressive disease process (eg, hereditary sensory motor neuropathy or other inherited or acquired muscular disease), with the exception of diabetic peripheral neuropathy • Bradycardia (ie, heart rate <60 bpm), or heart rate <50 bpm if the subject is taking heart rate lowering medication (eg, beta blockers) • Significant orthostatic hypotension as defined by: - Symptomatic (ie, feeling dizzy, light headed, or fainting) accompanied by either a decrease in systolic blood pressure of >20 mm Hg or decrease in diastolic blood pressure of >10 mm Hg within 3 minutes of standing up, or - a decrease in systolic blood pressure of at least 40 mm Hg within 3 minutes of standing up, or - a decrease in diastolic blood pressure of at least 20 mm Hg within 3 minutes of standing up • History of bone marrow transplant (BMT) within the past 10 years. If a subject had BMT >10 years ago, must not have had a history of graft versus host disease and not currently receiving immunosuppressive therapy. • History of leukemia • History of small cell lung cancer • History of neuroendocrine tumors • History of any of the following: - Seizure disorders within the past year - Multiple sclerosis within the past year - Intrathecal therapy, Ommaya reservoirs, and ventricular shunts within the past year - Radiotherapy to the cerebral or spinal areas within 3 months before the screening visit - Mild or moderate traumatic brain injury within the past year - Stroke within the past year - Transient ischemic attack within the past year - Severe traumatic brain injury within the past 15 years (consisting of >= 1 of the following: brain contusion, intracranial hematoma, either unconsciousness or posttraumatic amnesia lasting more than 24 hours) or with residual sequelae suggesting transient changes in consciousness - Any other condition suggesting compromised blood brain barrier (contact the sponsor*s medical officer to discuss if unclear) • Presence of known or suspected cerebral metastases • Any other condition suggesting compromised blood brain barrier (contact the sponsor*s medical officer to discuss if unclear) • Presence of disseminated or severe organ-related herpes virus disease (eg, cytomegalovirus retinitis or cytomegalovirus nephritis) • Presence of severe chronic obstructive pulmonary disease (COPD) • Oxygen saturation (SpO2) <90% on room air or <=2 L/min of oxygen therapy for subjects who have clinically significant compromised lung function. Subjects who are receiving >2 L/min of oxygen therapy will also be excluded irrespective of their oxygen saturation value at screening. • Alanine aminotransaminase (ALT) or aspartate aminotransaminase (AST) >=3 times the upper limit of normal (ULN) • Serum creatinine of >=2 mg/dL • Planned initiation of new chemotherapy regimen or radiotherapy, bisphosphonates, or hormonal or growth factor therapy during the double-blind treatment phase • Planned major surgical procedure during the double-blind treatment phase • Currently using patient-controlled analgesia or IV opioids as chronic baseline pain therapy • Currently receiving >=60 mg-equivalents of prednisone per day • Received an investigational drug (including vaccines) or used an investigational medical device within 30 days before the planned start of treatment, enrolled in an investigational study for an analgesic within the previous 4 weeks or 5 half-lives of the investigational drug (whichever is longer), or are currently enrolled in another investigational study at the time of screening.