A Randomized Placebo-Controlled Study of the Neurokinin-1 (NK1) Receptor Antagonist Serlopitant Prurigo Nodularis (PN)

A Randomized, Double-Blind, Placebo-Controlled, Study of Neurokinin-1 Receptor Antagonist Serlopitant in Subjects With Prurigo Nodularis

The purpose of this study is to demonstrate whether or not VPD-737, an NK1 receptor antagonist is safe and effective for treatment of prurigo nodularis versus placebo.

The sensation of itch is transmitted to the brain through the nervous system. Several chemicals are involved in transmitting this signal.This trial of VPD 737 is intended to treat this condition by blocking one of the chemicals involved in the transmission of the itch signal. This is an oral drug administered once daily It has been used in other trials and has shown to be safe at the doses used in this trial. The trial will involve once daily pills for 8 weeks. Subject will be asked to fill out questionnaires both electronically and on paper during the study period. Patients will also be monitored for safety and will have blood taken for testing and several points during the trial. Overall participation will last about 14 weeks

Inclusion Criteria:

• Subjects meeting all of the following criteria will be eligible for study entry:

  1. Males or females who are at least 18 years and no more than 80 years of age at Screening.

  2. Must have PN (defined as the presence of pruritic nodules due to chronic pruritus,) of more than 6 weeks duration despite treatment with current therapies such as antihistamines or corticosteroids ("treatment resistant" PN).

  3. Must have PN lesions on both arms, both legs, and/or the trunk (ie, the lesions must not be localized).

  4. Must have a VAS pruritus score of 70 or greater within 72 hours of Baseline.

  5. Males, non-fecund females (ie, surgically sterilized, if procedure was done 12 months before screening or subject is postmenopausal, without menses for 12 months before screening), or females of childbearing potential using an acceptable method of birth control for a period of 35 days before the first dosing, and all females must have a negative pregnancy test at the screening and baseline visits:

     Note 1: Acceptable methods of birth control include any one of the following:

     abstinence, vasectomized sexual partner, hormonal methods (ie, birth-control pill, hormonal IUD, Depo-Provera, implants, patch, intravaginal device [NuvaRing]), intrauterine device (IUD [copper banded coils]), diaphragm, cervical cap, or condom with spermicidal jelly or foam. Subjects using oral contraceptives must also use a reliable backup method of birth control during the study and until the first menses after the last dose of study medication or for 14 days menses after the last dose of study medication.

  6. Willing and able to understand and provide written informed consent.

  7. Willing and able to comply with study requirements and restrictions including the discontinuation of all current therapies for pruritus.

  8. Subjects must be in good health as determined by medical history, physical examination, and results of Electro Cardio Gram (ECG) and clinical laboratory tests (including urinalysis).

  9. Agreeing to confidential use and storage of all data and use of all anonymized data for publication including scientific publication.

Exclusion Criteria:

• Subjects not eligible for the study are those who:
• Have chronic pruritus due conditions other than PN, such as the following conditions:
• Lichen simplex chronicus
• Lichen amyloidosus
• Localized pruritus (e.g., only one arm affected)
• Neuropathic and psychogenic pruritus (notalgia paresthetica, brachioradial pruritus, somatoform prurigo, dilusional parasitosis, depression associated prurigo)
• Active dermatoses needing immediate therapy such as atopic dermatitis (without PN) or bullous pemphigoid;
• Have a history of use (within the specified time periods) of the medications listed below. Prior to randomization, a subject who used any of these medications must undergo a washout period equal to the length of the interval specified below (eg, 2 weeks for antihistamines, 4 weeks for naltrexone, and 4 weeks for cyclosporine A).
• Topical or systemic antihistamines, (used ≤2 weeks prior to the baseline visit) [loratindine, or cetirizine may act as rescue medication during treatment];
• Topical calcineurin inhibitors, topical capsaicin, menthol, camphor, polidocanol, topical antibiotics, antiseptic baths and cleansing lotions (used ≤2 weeks prior to the baseline visit);
• Topical steroids (used ≤2 weeks prior to the baseline visit);
• Naltrexone, paroxetine, fluvoxamine, amitriptyline, gabapentin, pregabalin, or UVtherapy (prescribed for the pruritus treatment) (used ≤4 weeks prior to the baseline visit);
• Systemic steroids (used ≤4 weeks prior to the baseline visit);
• Cyclosporine A and other immunosuppressants (used ≤4 weeks prior to the baseline visit).
• Have any medical condition or disability that would interfere with the assessment of safety or efficacy in this trial or would compromise the ability of the subject to undergo study procedures or to give informed consent.
• Have any chronic or acute medical condition that, in the opinion of the investigator, might interfere with the study results or place the subject at undue risk.
• Have a history of sensitivity to any components of the study material.
• Are females of childbearing potential who are unwilling to use adequate contraception or who are breast feeding.
• Have chronic renal disease, ie, serum creatinine greater than 2.4 mg/dL.
• Have aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal. Subjects with hepatitis B or C who have normal liver function may be enrolled.
• Have a current malignancy (such as Hodgkin's lymphoma, B or T cell lymphoma, or myeloma) or blood cell dyscrasia (eg, polycythemia or myelofibrosis) that might lead to systemic chronic pruritus.
• Subjects with untreated hyperthyroidism.
• Have pruritus of psychiatric etiology (eg, delusions of parasitosis, obsessive compulsive disorder, or major depression) or neuropathic etiology (eg, due to shingles, spinal cord injury or with neurologic deficit).
• Have pruritus due to urticaria, drug allergy, or infection (such as pityriasis rosea or tinea or active human immunodeficiency virus [HIV]). Note: Subjects with HIV who have undetectable viral load, CD 4 counts >200 cells/cc, and stable retroviral therapy may enroll.
• Are on medications known to cause pruritus (ie, Erbitux®, opioids, cocaine, amphetamines, and angiotensin converting enzyme [ACE] inhibitors) and are suspected of having drug-induced pruritus.
• Have taken investigational medications within 30 days prior to Screening.
• Are currently participating in any other clinical study.
• Have a history (within the previous 4 weeks) of use of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRIS), monoamine oxidase (MAO) inhibitors, opioids, immunemodulators (e.g. azathioprine, methotrexate, mycophenolate mofetil, cyclosporine A, antibodies), or neuroactive medications (e.g. pregabalin, gabapentin).
• Have a history (within the previous 4 weeks) of use of sedatives or tranquilizers.

Subjects must undergo an appropriate washout period from any sedatives or tranquilizers before enrolling in the study.

• Are currently treated with strong CYP3A4 inhibitors (e.g. conazole, ketoconazole, fluconazole, itraconazole, voroconazole etc. or erythromycin). The co-administration of moderate CYP3A4 inhibitors to VPD-737 may be allowed with investigator agreement and appropriate safety monitoring.
• Received ultraviolet B (UVB) or psoralen + ultraviolet A (PUVA) treatment within 30 days prior to Screening.
• Within the past 12 months, have expressed suicidal ideation with some intent to act.
• Started or changed creams, or emollients including over-the-counter (OTC) preparations or bath oil treatment for relief of pruritus within 2 weeks prior to Screening.
• Have any social or medical condition (eg, alcoholism, drug dependency, psychotic state) that, in the investigator's opinion, might interfere with the subject's ability to comply with the requirements of the protocol.
• Are employees of the study site or of the Sponsor's company.