Pharmacokinetics of Intravenous Difelikefalin in Chinese Adult Subjects on Haemodialysis

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1, single-arm, open-label study to evaluate the safety, PK, and tolerability of a repeated (3 times weekly) dose of difelikefalin administered as IV bolus injections to adult Chinese HD subjects. Treatment period is one week and there is a safety follow-up period of 1 week.

Detailed Description
-----------------
This is a Phase 1, single-arm, open-label study to evaluate the safety, PK, and tolerability of a repeated (3 times weekly) dose of difelikefalin administered as IV bolus injections to adult Chinese HD subjects. Total study duration for a single subject is up to 5 weeks including a screening period of up to 3 weeks, a treatment period of 1 week, and a safety follow-up period of 1 week. The duration of PK sampling is 12 days. The primary objective of the study is to evaluate the PK profile of a repeated (3 times weekly) dose of difelikefalin in Chinese HD subjects over a 1-week treatment period.

Official Title
-----------------
A Phase 1, Single-arm, Open-label Study to Evaluate the Pharmacokinetics and Safety of Intravenous Difelikefalin in Adult Chinese Subjects on Haemodialysis

Conditions
-----------------
End Stage Renal Disease on Hemodialysis

Intervention / Treatment
-----------------
* Drug: Difelikefalin Injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: End-stage renal disease (ESRD) subjects who have been on HD for at least 3 months before enrolment in the study and are currently on HD 3 times per week. Subjects with a prescription dry body weight between 40 and 100 kg, inclusive. If female, is not pregnant, or nursing If female: Is surgically sterile; or Has been amenorrhoeic for at least 1 year and is over the age of 55 years; or Has a negative serum pregnancy test within 7 days before first dose of investigational product, and agrees to use adequate contraceptive precautions (e.g., hormonal contraceptives, barrier with spermicide, intrauterine device, vasectomised partner, or abstinence) from the time of informed consent until 7 days after the last dose of investigational product. If male, agrees not to donate sperm from the first dose of investigational product administration (Day 1) until 7 days after last dosing, and agrees to use a condom with spermicide or abstain from heterosexual intercourse during the study until 7 days after the last dose of investigational product. Exclusion Criteria: Planned or anticipated to receive a kidney transplant during the study. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) greater than 2.5 × the reference upper limit of normal (ULN), or bilirubin (total) greater than 4 × the ULN at screening. Subjects with severe hepatic impairment (Child-Pugh Class C). Known history of allergic reaction to opiates such as hives. Note: Side effects related to the use of opioids such as constipation or nausea would not exclude the subjects from the study. Subject has known hypersensitivity to the study intervention or any component of the investigational product formulation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A Single-arm, Open-label Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1-week, single arm, open label treatment phase<br> | Drug: Difelikefalin Injection<br>* Participants receive Difelikefalin three times a week (0,5 micrograms/kg dry body weight). Difelikefalin is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the PK profile of difelikefalin - Cmax | Cmax = Maximum (peak) observed plasma concentration | 1 week | 
| Evaluation of the PK profile of difelikefalin - Tmax | Tmax = Time to reach maximum observed plasma concentration | 1 week | 
| Evaluation of the PK profile of difelikefalin - AUC0-t | AUC0-t = Area under the concentration-versus-time curve (AUC) from time zero to time t | 1 week | 
| AUCinf | AUCinf = AUC from time zero to infinity | 1 week | 
| AUCextrap(%) | AUCextrap(%) = percentage of AUCinf based on extrapolation | 1 week | 
| t½ | t½ = elimination half-life | 1 week | 
| Clearance | Clearance = the volume of blood or plasma that can be freed of a specified constituent in a specified time by its excretion into the urine through the kidneys | 1 week | 
| Vz | Vz = volume of distribution | 1 week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Difelikefalin, Pharmacokinetics