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Individuals diagnosed with PN (definition: presence of ≥ 20 pruriginous nodules, with predominantly nodular lesions overall that have been actively present and documented for at least 6 weeks |
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Generalized PN, defined as PN lesions with a nodular component involving 2 distinct anatomical areas: for example, either 2 limbs; or a single limb and some axial portion of the body |
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The mean value of the 7-day baseline WINRS score must be ≥ 7: ie, an assessment of the "worst" itch in the last 24 hours is recorded once-daily over the 7 contiguous days prior to the baseline visit. At least 5 measurements are recorded, with all individual measurements ≥ 6 |
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Subjects using antidepressant and/or neuroleptic medications must be on a stable dose for a minimum of 8 weeks prior to signing consent and must be willing to remain on their stable dose for the entire duration of the study |
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Subjects who are human immunodeficiency virus (HIV) positive may enroll if they meet the following criteria: (a) currently on a stable (> 6 months stable use) and well tolerated highly active antiretroviral therapy regimen; (b) CD4 count > 500 cells/mL; and (c) HIV RNA < 50 copies/mL documented for at least 6 months prior to enrollment. If enrolled, these subjects should continue to have their CD4 and HIV RNA monitored |
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Males, females of non-childbearing potential, or females of childbearing potential using an acceptable method of birth control (if sexually active) |
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Sexually active female subjects of childbearing potential are required to use 1 barrier method (eg, condom, cervical cap, or diaphragm) of contraception in addition to 1 other method (eg, intrauterine device in place at least 1 month, stable hormonal contraception for at least 3 months, or Essure procedure, or spermicide). For female subjects using a barrier method plus spermicide, that method must be used for at least 14 days prior to screening |
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Willing and able to understand and provide written informed consent |
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Pruritus due to localized PN (only 1 body part affected, for example only 1 arm)
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Active, uncontrolled, pruritic dermatoses in need of treatment (such as atopic dermatitis, or bullous pemphigoid for example) or other dermatologic conditions that in the opinion of the Investigator could confound the ability to assess PN related itch
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Major psychiatric disorder, which in the opinion of the Investigator, could interfere with the assessment of anti-pruritic efficacy and/or safety events during the study or with the ability of the subject to cooperate with study requirements
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Serum bilirubin > 2.5 × upper limit of normal range at screening unless explained by a clinical diagnosis of Gilbert's Syndrome
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Serum hepatic alanine aminotransferase or aspartate aminotransferase enzymes > 100 U/L at screening
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Estimated glomerular filtration rate ≤ 44 mL/min/1.73 m2 at screening
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Significant medical condition or other factors that in the opinion of the Investigator may interfere with the conduct of the study
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Subjects who have an active malignancy (either solid tumor or hematologic) are excluded
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Subjects who have a past history of malignancy and who have no evidence of active disease but who continue on therapy to prevent disease recurrence (ie, tamoxifen for breast cancer, testosterone blockade for prostate cancer, etc), may be eligible if approved by the Medical Monitor
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Known intolerance of or hypersensitivity or allergy to nalbuphine or vehicle components
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Medication-related Exclusions
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Known intolerance (GI, CNS symptoms) or hypersensitivity/drug allergy to opioids
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Potential subjects taking monoamine oxidase inhibitors are excluded, as concomitant opiate use may increase the risk for serotonin syndrome
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Potential subjects taking cyclosporin A are excluded unless they undergo a 6-week washout prior to beginning the screening period. Washout should occur after signing informed consent, if done for study participation purposes, and prior to e-diary NRS collection. Numerical Rating Scale collection should not take place prior to 6 weeks after discontinuation of cyclosporin A. Subjects are prohibited from using cyclosporin during the study
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Potential subjects taking biologics are excluded unless they undergo a 3-month washout prior to beginning the screening period. Washout should occur after signing informed consent, if done for study participation purposes, and prior to e-diary NRS collection
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Potential subjects who have previously received dupilumab or nemolizumab are excluded
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Exposure to any investigational medication, including placebo, within 4 weeks (3 months for biologics) prior to e-diary NRS collection during the screening period
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Potential subjects receiving UV-therapy (PUVA, UVA, UVB, Excimer) are excluded unless they have discontinued > 4 weeks prior to e-diary NRS collection during the screening period. Discontinuation should occur after signing informed consent, if done for study participation purposes, and prior to e-diary NRS collection. Subjects are prohibited from using UV-therapy for the duration of the study
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Potential subjects cannot have received opiates within 14 days prior to the screening period. Subjects are prohibited from using opioids, including naltrexone, for the duration of the study
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Potential subjects cannot have received gabapentin, pregabalin, calcineurin inhibitors, cannabinoid agonists, capsaicin, cryosurgery, topical doxepin, thalidomide, antihistamines (systemic or topical), and topical corticosteroids within 14 days prior to the screening period. These medications are prohibited for the duration of the study
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Potential subjects are excluded if they have had any addition or discontinuation of their regularly used prescription drugs, or any changes in the doses of their regularly used prescription drugs in the 14 days prior to the beginning of the screening period
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Cardiac-related Exclusions
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Subjects with a history of congestive heart failure of Class 2 or higher as graded using the New York Heart Association scale
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Subjects with a history of angina pectoris Grade 2 or higher as graded using the Canadian Cardiovascular Society grading scale
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History of ventricular tachycardia, Torsade de Pointes, or family history of sudden death
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Myocardial infarction or acute coronary syndrome within the previous 3 months, as reported by the subject
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Serum potassium below the laboratory lower limit of normal. QTcF interval > 450 ms on screening ECG
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Heart rate < 45 bpm on any screening measurement. Subjects with a resting heart rate of < 45 bpm will have it repeated once after 5 minutes in the supine position, and if it remains < 45 bpm during the repeat, they will be considered a screen failure
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Use of a medication having a "known risk" of Torsade de Pointes (categorized as "KR" on the Credible Meds® website; see Appendix 10, for hyperlink to the CredibleMeds Filtered QTDrug List) is not permitted at entry or during the study
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Medications associated with a potential risk of QT prolongation, but not clearly associated with Torsade de Pointes, are permitted at study entry if the following criteria are met: subject has been given medication at stable doses for a full 4 weeks prior to screening medication dose will not be increased after screening, or during the study, and it is anticipated that they will receive the medication for the entirety of the study QTcF at screening is ≤ 450 ms
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