A Placebo-controlled 12-Week Study to Evaluate the Safety and Efficacy of Oral Difelikefalin in Advanced Chronic Kidney Disease Subjects with Moderate-to-Severe Pruritus with an up to 52-Week Long-term Extensio
- Conditions
- Chronic Kidney DiseaseMedDRA version: 23.1Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2022-000149-34-PL
- Lead Sponsor
- Cara Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 400
1. Willing and able to provide written informed consent prior to participating in this study.
2. Able to communicate clearly with the study investigator and staff and complete the required study procedures and questionnaires.
3. Subjects aged 18 to 85 years, inclusive, at the time of consent.
4. A) Subjects not currently on dialysis with advanced CKD (ie, estimated glomerular filtration rate (eGFR) =29 mL/min/1.73 m2 calculated using chronic kidney disease-Epidemiology Collaboration (CKD-EPI) creatinine equation [2021]) based on either a screening laboratory serum creatinine value from this study or at least 2 documented serum creatinine values collected at least 90 days apart within 1 year prior to screening.
B) Subjects receiving hemodialysis 3 times per week for at least 3 months prior to the start of screening;
5. Subject self-reports experiencing at least near-daily (eg, most days of a week) pruritus for at least 6 months prior to screening.
6. Inadequate response to current or prior treatments (including emollients/moisturizers, topical medications, or systemic treatments) for pruritus prior to screening.
7. Female subject is not pregnant or nursing during any period of the study.
8. If female of childbearing potential, must have a negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test result within 7 days prior to randomization
9. For females, subject must be of nonchildbearing potential defined as:
a. Postmenopausal: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. For women aged 55 years or younger, postmenopausal state should be confirmed by a high follicle-stimulating hormone (FSH) level (> 40 IU/L or > 40 mIU/mL). No FSH confirmation is required in women older than 55 years; or
b. Surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).
Or, of childbearing potential involved in sexual intercourse that could lead to pregnancy and:
• Agrees to use an adequately effective method of contraception: (eg, hormonal contraceptives from at least 30 days prior to Day 1 until 7 days after the last dose of study drug [oral, intravaginal, transdermal, injectable, or implant], barrier method with spermicide, intrauterine device [IUD], intrauterine hormone releasing system [IUS], bilateral tubal ligation, vasectomized partner provided his vasectomy was performed = 4 months prior to screening, or abstinence) from the time of informed consent until 7 days after the last dose of study drug.
Note: The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post ovulation methods) is not acceptable.
10. For male subjects involved in any sexual intercourse that could lead to pregnancy, subject must agree to use one of the effective contraceptive methods listed in Inclusion Criterion #9, from Day 1 (first day of treatment) until at least 7 days after the last study product administration. If the female partner of a male subject uses any of the hormonal contraceptive methods listed above and is the only form of contraception used, this contraceptive method should be used by the female partner from at least 4 weeks before Day 1 until at least 7 days after the last dose of study drug. Male subjects must agree not to donate sperm during the study and for 7 days after receiving the study drug. No restrictions a
1. Scheduled to receive renal replacement therapy (dialysis or kidney transplant) during the study.
2. Has a concomitant disease, significant medical condition or physical/laboratory/ECG/vital signs abnormality that, in the opinion of the investigator, puts the subject at undue risk or interferes with interpretation of study results, impedes completion of the study procedures, or compromises the validity of the study measurements.
Examples: unstable or high-risk subjects, such as those with recent myocardial infarction within the last 6 months, New York Heart Association (NYHA) Class IV heart failure, uncontrolled hypertension despite being on antihypertensive medications(s), and significant uncontrolled psychiatric disorders.
3. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior to Day 1.
4. Subject had a major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study.
5. Subjects with a history of hypernatremia within the past 3 months.
6. Subjects unable to sense or respond to thirst appropriately.
7. New or change of treatment received for itch, including antihistamines and corticosteroids (oral, intravenous, or topical), within 14 days prior to the start of Run-in.
8. New or change of prescription for gabapentinoids, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, anticonvulsants/mood stabilizers, tricyclic antidepressants, opioids or benzodiazepines within 14 days prior to the start of Run-in.
9. Serum alanine aminotransferase or aspartate aminotransferase greater than 2.5 times the reference upper limit of normal (ULN) and/or total bilirubin greater than 1.5 times the upper limit of normal (ULN) at screening.
10. Received an 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.
11. Has pruritus attributed to a cause other than chronic kidney disease (eg, pruritus associated with dermatological, hepatobiliary, neuropathic, and/or hematologic disorders).
12. Has localized itch restricted to the palms of the hands.
13. Receiving an opioid antagonist (eg, naloxone, naltrexone) or opioid-mixed agonist-antagonist (eg, buprenorphine, nalbuphine) within 14 days prior to the start of screening and/or anticipates receiving such medications during the study.
14. Received ultraviolet B treatment within 30 days prior to screening and/or anticipates receiving such treatment during the study.
15. Has a known or suspected allergy to difelikefalin or any component of the investigational product.
16. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. Subjects with successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded.
17. Subject has a current condition resulting in chronic dehydration (eg, ongoing vomiting, chronic diarrhea) or a condition that, in the opinion of the investigator, could predispose to dehydration.
A subject will be excluded from the Long-term Extension Phase of the study if any of the additional following criteria are met at the time of entry into the Long-term Extension Phase.
18. Experienced AEs during the course of Treatment Period 1 that may preclude continued exposure to the study drug.
19. Was noncompliant with protocol procedures during the Efficacy Assessment Phase o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method