Screening Period. After the informed consent form (ICF) is signed, subjects will enter the Screening Period for assessment of eligibility. During the Screening Visit, subject’s medical and surgical history will be reviewed including allergic history. Review of medical history will include the specific cohort disease history and history of co-morbidities. Prior and concomitant medications, therapies and procedures will be recorded. Subjects will be instructed on the required washout for specific excluded medications. Xxxxx xxxxx and body weight will be measured, and subjects will undergo a full physical examination. Clinical laboratory tests and an ECG will be performed. Urine drug screen and pregnancy test (if applicable) will also be performed. To be eligible for study participation, subjects must have moderate to severe pruritus, defined as WI-NRS ≥ 7 at the Screening Visit and a mean weekly WI-NRS ≥ 5 for each of the two consecutive weeks immediately prior to randomization. A minimum of 85% compliance with daily WI-NRS recording during the last 14 days of Screening Period prior to randomization is required for eligibility unless approved by the Sponsor. At the Screening Visit, subjects will be asked to rate their pruritus severity (WI-NRS) in the previous 24 hours on a numerical rating scale. Subjects also will be instructed to record their daily rating of WI-NRS and two sleep parameters, difficulty falling asleep NRS and sleep quality NRS, from the beginning of screening to Day 1. The daily recordings (WI-NRS, difficulty falling asleep NRS, and sleep quality NRS) will continue throughout the study for eligible subjects that proceed to dosing. Furthermore, subjects with CIU will also be instructed to complete on a daily basis the UAS7 questionnaire (on itch and hives severity) from the beginning of screening to Day 1. Daily completion of the UAS7 questionnaire will continue throughout the study for eligible CIU subjects that proceed to dosing. Additional assessments at the Screening Visit include those related to pruritus (Pruritus VAS, and 5-D Pruritus), sleep (Sleep Loss VAS), dermatology life quality index (DLQI) and Itchy quality of life (ItchyQoL). Collection of adverse events and concomitant medications will begin after signing the ICF and will continue until the EOS Visit. For a Schedule of Activities, please see Appendix 1.
Screening Period. The Screening period (Days -30 to -1) consists of two study visits: • Screening Visit 1 • Screening Visit 2. The time to Screening Visit 2 can be extended to more than 30 days to obtain an appropriately and fully completed bladder diary or to obtain a valid bladder diary (see Section 17.6). In addition, where a UTI occurs after completion of the bladder diary and impacts the ability to perform urodynamics the time to Screening Visit 2 can be extended until the UTI is resolved.
Screening Period. Screening of potential patients will be performed only after informed consent is obtained and within 21 days prior to first dose of trial medication (unless otherwise noted below). All necessary laboratory values and assessment reports must be available and reviewed prior to cycle1/ day 1. The following will be completed as part of the screening visit:
1. Written informed consent
2. Medical history including concurrent baseline conditions (using NCI CTCAE version 4.0; Appendix 3), prior cancer therapy (including documentation of prior surgery, adjuvant or neoadjuvant chemotherapy and radiotherapy)
3. Complete physical examination including height (cm) and weight (kg)
4. ECOG Performance Status (see Appendix 4)
5. Xxxxx xxxxx (blood pressure, pulse, respiratory rate, and temperature)
6. Computed tomography (CT) / magnetic resonance imaging (MRI) scan to document disease status (including chest, abdomen, pelvis, and other regions as clinically indicated. In addition, brain scan is required to exclude brain metastases if clinically indicated only). If a CT scan was taken within 28 days prior to first dose, a new scan is not necessary. However, if a new scan is to be done, it should be performed within 10 ± 2 days prior to starting trial medication. Obtain De-identified Dicomm encoded CT scan for central lab (Appendix 7).
7. Electrocardiogram (ECG)
8. PT/INR and aPTT
9. Complete blood count (CBC) with differential and platelet count
10. Comprehensive serum chemistries (refer to Table 9) 11. TSH, T3, Free T4, and PTH
Screening Period. The Screening Period will begin with the signature of the informed consent form (ICF). The diagnosis of depression will be determined using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) Axis I Disorders (SCID-I). Eligibility will be determined by applying the inclusion/exclusion criteria. A full medical and family history will be taken including recording of all major depression episodes, other Axis I and Axis II disorders, and postpartum depression episodes in immediate female family members. Treatment Period: Once subjects are confirmed as eligible for the study, they will be randomized to active study drug or placebo on a 1:1 basis. Randomized subjects will receive 30 mg QD of study drug (SAGE-217 Capsules or placebo). Those subjects who cannot tolerate 30 mg QD will receive 20 mg QD for the remainder of the Treatment Period. Subjects who experience intolerable adverse events (AEs) at the 20 mg QD dose level may be discontinued from study treatment at the discretion of the Investigator. Subjects will be instructed to Name of Sponsor: Sage Therapeutics 000 Xxxxx Xxxxxx Xxxxxxxxx, XX 00000
