Please select the eligibility criteria that correspond to the clinical trial below.
Title: Safety and Efficacy of PG102P for the coNtrol of prUritus in Patients underGoing Hemodialysis (SNUG Trial): Study Protocol for a Randomized Control Trial
Brief Summary: In this study (SNUG trial), the investigators aim to investigate the anti-pruritic effect of PG102P in comparison with placebo in 80 patients undergoing HD.


Options:
A: Key Inclusion Criteria:

To be eligible for inclusion into the Double-blind Phase of the study, a patient must meet the following criteria:

* Has end-stage renal disease (ESRD) and has been on hemodialysis 3 times per week for at least 3 months prior to the start of screening;
* Has at least 2 single-pool Kt/V measurements ≥1.2, or at least 2 urea reduction ratio measurements ≥65%, or 1 single pool Kt/V measurement ≥1.2 and 1 urea reduction ratio measurement ≥65% on different dialysis days during the 3 months period prior to screening;
* Prior to randomization:

  * Has completed Worst Itching Intensity NRS worksheets up to 8 days prior to 1st dose;
  * Has a mean baseline Worst Itching Intensity NRS indicative of moderate to severe uremic pruritus.
* To be eligible for inclusion into the Open-label Extension Phase of the study, each patient will have to fulfill the additional key following criteria at the time of entry into the Open-label Extension Phase:

  * Has received at least 30 doses of the planned 36 doses of study drug during the Double-blind Phase of this study;
  * Continues to meet inclusion criteria.

Key Exclusion Criteria:

A patient will be excluded from the Double-blind Phase of the study if any of the following criteria are met:

* Known noncompliance with dialysis treatment that in the opinion of the investigator would impede completion or validity of the study;
* Scheduled to receive a kidney transplant during the study;
* New or change of treatment received for itch including antihistamines and corticosteroids (oral, IV, or topical) within 14 days prior to screening;
* Received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study;
* Has pruritus only during the dialysis session (by patient report);
* Is receiving ongoing ultraviolet B and anticipates receiving such treatment during the study;
* Participated in a previous clinical study with CR845.
* A patient will be excluded from the Open-label Extension Phase of the study if any of the additional key following criteria are met at the time of entry into the Open-label Extension Phase:

  * Completed the Double-blind Phase of this study but exhibited adverse events during the course of the Treatment Period that may preclude continued exposure to the study drug;
  * Was noncompliant with protocol procedures during the Double-blind Phase of this study which is indicative of an inability to follow protocol procedures.
B: Inclusion Criteria:

* Subject has been receiving in-center hemodialysis for ≥ 3 months and are currently on a schedule of 3 times a week.
* Subject self-categorized themselves on the Patient Assessed Disease Severity Scale during Screening
* Subject meets standard of care hemodialysis efficiency guidelines during the three months prior to completing Screening
* Have demonstrated pruritus intensity on the Itch NRS during screening
* Male or female who are at least 18 years old at the time of Screening

Exclusion Criteria:

* Subject had a significant alteration in dialysis regimen during the Screening Period
* Subject receiving or anticipated to be receiving nocturnal dialysis or home hemodialysis treatment during the study.
* Subject has pruritus that is believed to be caused by a condition unrelated to end-stage renal disease
* Has had a history of substance abuse within 6 months prior to completing Screening
* Subject has a known drug allergy to opioids
* Subject is a pregnant or lactating female.
C: Inclusion Criteria:

* On stable hemodialysis for at least 3 months
* Has stable functioning arteriovenous fistula, graft or other venous access
* Has continued (uncontrolled) uremic pruritus despite standard of care in the institution
* Has severe pruritus, as determined by a qualifying score of ≥3 on the Itch Severity Score Scale (0 to 4) either day or night during the week prior to Screening Visit
* Has no known drug addiction to any prescription, nonprescription, herbal or natural drugs, and successfully passes a drug screen test
* Women and men whose partners are of childbearing potential agree to practice the medically acceptable methods of birth control and agree to continue with the regimen throughout the duration of the study
* Capable of understanding and responding to the subject questionnaires, understands the purpose and risks of the study, and has given written informed consent
* Has rated his/her NRS score each day for at least 5 days out of the 7 days of the Run-in Phase
* Has severe pruritus, as determined by qualifying mean worst NRS score in a day of ≥5 (on 11 point NRS) at the end of the 1-week Run-in Phase

Exclusion Criteria:

* Current, clinically significant medical comorbidities
* Abnormal liver dysfunction
* Pruritus attributed mainly to any disease unrelated to kidney disease
* Calcium x phosphorus product \>80 mg2/dL2 or hemoglobin \<7 g/dL or parathyroid hormone levels \>1000 pg/mL at Screening
* Received ultraviolet B treatment within 30 days prior to Screening
* Started or changed psychotropic medication within 14 days prior to Screening
* Is receiving opioid antagonists or opioid agonists within 7 days prior to Screening and not willing to abstain from these medications during the study.
* Started or changed medications, creams or emollients including over-the-counter oil bath treatment for relief of pruritus within 7 days prior to Screening
* Has known hypersensitivity to opioids or the study drug ingredients
* Is currently participating in an investigational drug or device clinical study or was participating in such a study within 30 days prior to the start of Screening
* Female subject who is known to be pregnant or nursing
* Is considered not suitable for inclusion in the study in the opinion of Investigator
* Has current suicidal ideation with some intent to act or with specific plan and intent or had suicidal behavior at any time in subject's life
D: Inclusion Criteria:

1. Age over 19 years
2. Patients with adequate HD (Kt/V \> 1.2)
3. Maintenance patients undergoing HD with chronic pruritus
4. Mean visual analog scale (VAS) over 4 of the last 5 days in the 14-day pre-observation period
5. Participants who allowed to continue the anti-pruritic drug treatment at the same dosage and administration schedule as used at baseline throughout the study period
6. Patients who agreed to participate in this trial and had written an informed consent

Exclusion Criteria:

1. Intact parathyroid hormone (iPTH) \> 1000 pg/mL within 1 month
2. Serum potassium \> 7.0 mg/dL
3. HIV Ab (+)
4. Aspartate transaminase (AST) (glutamic oxaloacetic transaminase) or alanine transaminase (ALT) (glutamic pyruvic transaminase) \> 3 times the upper limit of normal
5. Scheduled to have kidney transplantation within 3 months
6. Cancer history with current treatment
7. Active infection with current treatment
8. Current itching with dermatologic diseases other than uremic pruritus
9. Pregnancy, childbearing potential during the study period, or breastfeeding
10. Allergy or hypersensitivity reaction to PG102P
11. History of participating another clinical trial within 2 months or planning to participate another clinical trial
12. Not eligible to participate this trial as researchers' decision

Answer: D