Pharmacokinetics of Intravenous Difelikefalin in Chinese Adult Subjects on Haemodialysis

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

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.

Study Overview

• Status: Recruiting
• Conditions: End Stage Renal Disease on Hemodialysis
• Intervention / Treatment: Drug: Difelikefalin Injection

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: KOR-CHINA-101 Clinical Study Team; Phone Number: +41 58 851 80 00; Email: kor-china-101.study@viforpharma.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Investigator Site 1
  • Beijing, China
    • Recruiting
    • Investigator Site 2
  • Beijing, China
    • Recruiting
    • Investigator Site 3
  • Shijiazhuang, China
    • Recruiting
    • Investigator Site 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

  1. Is surgically sterile; or
  2. Has been amenorrhoeic for at least 1 year and is over the age of 55 years; or
  3. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1-week, single arm, open label treatment phase	Drug: Difelikefalin Injection; 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.

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

Collaborators and Investigators

• Sponsor: Vifor Fresenius Medical Care Renal Pharma
• Collaborators: Tigermed Consulting Co., Ltd
• Investigators: Study Director: Milica Enoiu, PhD, Vifor Pharma Group

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: June 1, 2023
• First Posted (Actual): June 2, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Difelikefalin
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: KOR-CHINA-101; JXHL2101166 (Other Identifier: Center for Drug Evaluation (CDE), China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No