E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inadequately controlled, moderate to severe, chronic, cancer-related pain |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058019 |
E.1.2 | Term | Cancer pain |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the analgesic efficacy, safety, and tolerability of a single SC dose (9 mg in 0.3 mL) of JNJ-42160443 compared with placebo as adjunctive therapy to standard pain therapy in subjects with inadequately controlled, moderate to severe, chronic, cancer-related pain. The primary efficacy objective of this study is to evaluate the analgesic effect of JNJ-42160443 compared with placebo, as measured by the change from baseline to the end of the double-blind treatment phase in the average cancer-related pain intensity score, using an 11-point numerical rating scale (NRS), with 0=no pain and 10=pain as bad as you can imagine. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: To evaluate the efficacy of JNJ-42160443 compared with placebo, as measured by the Brief Pain Inventory (BPI) Short Form, Patient and Clinical Global Impression of Change (PGIC and CGIC), and baseline and breakthrough opioid use To evaluate the immunogenicity (antibodies to JNJ-42160443) associated with JNJ-42160443 treatment The pharmacokinetics of JNJ-42160443 after SC doses will also be examined |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Have a life expectancy of at least 4 months Have a diagnosis of active cancer Have a diagnosis of moderate to severe pain directly related to an active cancer and inadequately controlled by standard pain therapies; the primary source 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, or osteoporotic fractures) Currently receiving opioid analgesics at screening: The baseline, around-the-clock dosage should be &#8805;60 mg of oral morphine equivalents, not including breakthrough pain medication doses; see Attachment 5, Equianalgesic Potency Conversion Table. The baseline opioid dosage should be given as a sustained-release formulation at a stable dosage for at least 1 week before screening. A stable, baseline opioid dosage is defined as a dosage that does not fluctuate by more than 50% from the average dosage over the 1 week before screening; the dosage may fluctuate by more than 50% for up to 2 days, if medically necessary. The baseline opioid dosage 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 adjuvant pain therapies (eg, anticonvulsants, antidepressants, NSAIDs, corticosteroids, pharmaceutical cannabinoids [eg, Marinol, Sativex, Cesamet]), must be at stable dosages for 2 weeks before screening and expected to remain stable during the double-blind treatment phase Have an average daily pain intensity score of &#8805;5 averaged over the last 3 days before randomization (Day 1) using an 11-point NRS, with 0=no pain and 10=pain as bad as you can imagine Have an MMSE score &#8805;24 Have an expected course of disease and pain that will permit compliance with the protocol over the double-blind treatment phase Subjects who are sexually active must consent to utilize a medically acceptable and highly effective (<1% per year failure rate) method of contraception throughout the entire study from screening through 6 months after the last dose of study drug. Medically acceptable, highly effective methods of contraception that may be used by the subject and/or partner include oral, transdermal, progestin implant, or injectable contraception; intrauterine device; tubectomy; or vasectomy (at least 6 months post surgery). For women of childbearing potential, contraception must be consistently used for 3 months before the first dose of study drug. Subject or partner may also be postmenopausal (states having not experienced a menstrual period for a minimum of 12 months). Postmenopausal women will not be required to use contraception. Further, subjects must agree to not donate sperm or eggs or attempt conception (pregnancy) for 6 months after the last dose of study drug. Women of childbearing potential must have a negative serum &#946;-human chorionic gonadotropin (&#946;-hCG) pregnancy test at screening and at randomization (Day 1). Willing/able to adhere to the prohibitions and restrictions specified in this protocol Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent form for pharmacogenomic research indicating willingness to partic |
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E.4 | Principal exclusion criteria |
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 area within the past year Mild or moderate traumatic brain injury within the past year Stroke within the past year Transient ischemic attack within the past year JNJ-42160443: Clinical Protocol 42160443PAI2001 Amendment INT-2 FINAL 18 February 2009 49 Severe traumatic brain injury within the past 15 years (consisting of &#8805;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 Presence of cerebral metastases (Note: Diagnostic testing will not be required for ruling out cerebral metastases.) Any other condition suggesting compromised blood brain barrier (contact the sponsors medical officer 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), according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) Standards for the Diagnosis and Management of Patients with COPD (ATS/ERS 2004) Oxygen saturation (pO2) <90% on room air or &#8804;2 L/min of oxygen therapy for subjects who have clinically significant compromised lung function Planned initiation of new chemotherapy regimen or radiotherapy, bisphosphonates, or hormonal or growth factor therapy during the double-blind treatment phase Planned major surgical procedures during the double-blind treatment phase Currently using patient-controlled analgesia or IV opioids as chronic baseline pain therapy Currently receiving &#8805;60 mg-equivalents of oral prednisone per day Inadequate baseline bone marrow reserve with WBC count &#8804;3,000/&#956;L, platelet count &#8804;50,000/&#956;L, and hemoglobin level &#8804;8 mg/dL History of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) (Note: HIV testing is not required for this study.) Prior treatment with any other investigational NGF inhibitor therapy Known allergies, hypersensitivity, or intolerance to JNJ-42160443 or its excipients, including mammalian cell-derived (ie, Chinese hamster ovary) products Received an investigational drug (including vaccines) or used an investigational medical device within 30 days before the planned start of treatment or are currently enrolled in an investigational study for an analgesic within the previous 8 weeks or 5 half-lives of the investigational drug (whichever is longer) Pregnant or breast-feeding Any condition that, in the opinion of the investigator, would compromise the wellbeing of the subject or the study or prevent the subject from meeting or performing study requirements Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy evaluation is the average cancer-related pain intensity in the last 24 hours using an 11-point NSR with 0= no pain and 10= pain as bad as you can imagine |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |