HSK21542 / Haisco - LARVOL DELTA

Reproductive and developmental toxicity assessment of HSK21542, a novel peripherally-restricted kappa opioid receptor agonist in rats and rabbits. (PubMed, Regul Toxicol Pharmacol) - "On the other hand, exposure to HSK21542 during pregnancy in rabbits did not show any teratogenic risk, only causing a minor impact on bone ossification in fetuses. In conclusion, HSK21542 has a favorable safety profile with only minor effects on the embryo-fetal developmental outcomes."

Journal • Preclinical • Dermatology • Pain • Pruritus

Population pharmacokinetic modeling and exposure-response analysis of Anrikefon: insights and implications in clinical analgesia. (PubMed, Expert Rev Clin Pharmacol) - "Anrikefon (HSK21542), a potent and selective peripheral kappa opioid receptor (KOR) agonist developed by Haisco, effectively blocks pain and itch signals...Safety analysis confirmed this dose was well tolerated with no safety issues. This study provides valuable insights into dose selection, PK variability, and safety and efficacy endpoints."

Journal • PK/PD data • Pain

A Clinical Trial Evaluating the Efficacy and Safety of HSK21542 in Patients with Chronic Kidney Disease-Associated Pruritus (clinicaltrials.gov) - P3 | N=545 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Completed | N=310 ➔ 545 | Trial completion date: Dec 2022 ➔ Jun 2024

Enrollment change • Trial completion • Trial completion date • Chronic Kidney Disease • Dermatology • Nephrology • Pruritus • Renal Disease

Efficacy and Safety of HSK21542 for Moderate-to-Severe CKD-Associated Pruritus: A Phase 3 Trial in Hemodialysis Patients (KIDNEY WEEK 2024) - P3 | "Patients treated with HSK21542 had a significant reduction in itch intensity and improved itch-related quality of life as compared with those who received placebo."

Clinical • Late-breaking abstract • P3 data • Chronic Kidney Disease • Dermatology • Hypotension • Nephrology • Pruritus • Renal Disease

Preclinical evaluation of abuse potential of the peripherally-restricted kappa opioid receptor agonist HSK21542. (PubMed, Regul Toxicol Pharmacol) - "The preclinical abuse potential assessments for HSK21542 included the following studies: 1) intravenous self-administration study to explore the relative reinforcing efficacy in rats self-administering remifentanil; 2) rat drug discrimination study to examine the pharmacological similarity of the interoceptive or subjective effects of HSK21542 in rats discriminating pentazocine; 3) rat conditioned place preference (CPP) paradigm to test the rewarding effects; 4) rat natural physical dependence-spontaneous withdrawal study in rats chronically treated with HSK21542; 5) naloxone-precipitated withdrawal assay following chronic HSK21542 exposure to evaluate its physical dependence potential. In addition, HSK21542 did not produce spontaneous withdrawal or naloxone-precipitated withdrawal in rats with chronic treatments. Collectively, these preclinical findings suggest that HSK21542 has no abuse potential in animals, which demonstrate low abuse potential in humans."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry

The efficacy and safety of HSK21542 in postoperative analgesia in laparoscopic surgery patients: a phase II multicenter clinical study (ASA 2024) - P1 | "The SPID0-12h and SPID0-24h of patients in group 4 (received HSK21542 of 1.0μg/kg at postoperative 0h, 8h,16h) were lower than other HSK21542 groups (-7.44±2.99 and -15.56±6.11) with the lower proportion of patients received rescue analgesics (16.7%) as well as the average consumption of morphine within 12h after surgery (0.8±1.86mg ). As to stage 2, the efficacy endpoints of both HSK21542-0.5 μg/kg and HSK21542-1.0 μg/kg groups were superior to the placebo group. No severe adverse events were reported."

Clinical • P2 data • Surgery • Anesthesia • Pain

Phase I clinical trial evaluating the safety, tolerance, pharmacokinetics and pharmacodynamics of HSK21542 injection in healthy volunteers. (PubMed, Basic Clin Pharmacol Toxicol) - "No subject withdrew early due to AEs. These results suggest that HSK21542 may be a potential treatment for pain and pruritic conditions."

Journal • P1 data • PK/PD data • Dermatology • Pain • Pruritus

CINV: Evaluating the Efficacy and Safety of HSK21542 Injection in Chemotherapy-induced Nausea and Vomiting (clinicaltrials.gov) - P2 | N=180 | Not yet recruiting | Sponsor: First Affiliated Hospital of Wenzhou Medical University

New P2 trial • Chemotherapy-Induced Nausea and Vomiting

HSK21542-105: Metabolism and Excretory of HSK21542 in Maintenance Hemodialysis Patients (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Chronic Kidney Disease • Nephrology • Renal Disease

A Clinical Trial Evaluating the Efficacy and Safety of HSK21542 in PONV (clinicaltrials.gov) - P=N/A | N=200 | Completed | Sponsor: Sichuan Provincial People's Hospital | Recruiting ➔ Completed | Trial completion date: Aug 2024 ➔ May 2024 | Trial primary completion date: May 2024 ➔ Feb 2024

Trial completion • Trial completion date • Trial primary completion date

HSK21542, a new peripherally-restricted kappa opioid receptor agonist in patients with postoperative pain: a phase 3, multicentre, double-blind, randomized controlled trials (Euroanaesthesia 2024) - "No severe adverse events were reported. Conclusion(s): Treatment of HSK21542 demonstrated a positive efficacy and safety profile and could be an effective treatment option for patients with moderately to severely postoperative pain after abdominal laparoscopic surgery."

Clinical • P3 data • Anesthesia • Pain

Model informed drug development: HSK21542 PBPK model supporting dose decisions in specific populations. (PubMed, Eur J Pharm Sci) - "Combined with the predicted results and the exposure-response relationship observed for HSK21542 and its analog (CR845), dosage regimens were designed for the target population with renal and hepatic impairment, supporting the successfully conducted trials (CTR20201702 and CTR20211940). Moreover, the observed exposure of HSK21542 in the elderly closely matched the predicted results within the same age group. Additionally, based on the predicted results, potential reductions in systemic exposure in pediatric patients should be carefully considered to avoid potential treatment failure in future clinical trials."

Journal • Hepatology • Pediatrics • Renal Disease

An Economic Study of HSK21542 Injection for Prevention of Postoperative Nausea and Vomiting (clinicaltrials.gov) - P4 | N=200 | Recruiting | Sponsor: Mengchang Yang

New P4 trial

A Study of HSK21542 in a Peritoneal Dialysis Pruritus Population. (clinicaltrials.gov) - P2 | N=250 | Not yet recruiting | Sponsor: Xizang Haisco Pharmaceutical Co., Ltd

New P2 trial • Dermatology • Pruritus

Metabolism and Excretory of HSK21542 in Maintenance Hemodialysis Patients (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P1 trial • Chronic Kidney Disease • Nephrology • Renal Disease

A Clinical Trial Evaluating the Efficacy and Safety of HSK21542 in PONV (clinicaltrials.gov) - P=N/A | N=200 | Recruiting | Sponsor: Sichuan Provincial People's Hospital

New trial

Pharmacokinetics, Mass Balance and Metabolism of [C]HSK21542, a Novel Kappa Opioid Receptor Agonist, in Humans. (PubMed, Eur J Drug Metab Pharmacokinet) - P1 | "HSK21542 was barely metabolized in vivo and mainly excreted with unchanged HSK21542 as its main circulating component in plasma. It was speculated that renal excretion was the principal excretion pathway, and faecal excretion was the secondary pathway."

Journal • PK/PD data

Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study. (PubMed, Front Pharmacol) - P2 | "HSK21542-0.3 μg/kg exhibited promising efficacy in patients with moderate to severe pruritus and warrants a further Stage 2 trial. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04470154."

Journal • Dermatology • Pain • Pruritus • Renal Disease

A Study to Evaluate the Pharmacokinetics of HSK21542 in Subjects With Renal Impairment (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P1 trial • Renal Disease

Pharmacokinetics, Mass Balance, and Metabolism of [14C]HSK21542 in Healthy Adult Male Volunteers. (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd.

New P1 trial • Pain

A Clinical Trial Evaluating the Efficacy and Safety of HSK21542 in Patients for Postoperative Pain Treatment (clinicaltrials.gov) - P3 | N=387 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Recruiting ➔ Completed | Trial completion date: Jun 2023 ➔ Mar 2023

Trial completion • Trial completion date • Pain

A Clinical Trial Evaluating the Efficacy and Safety of HSK21542 in Patients for Postoperative Pain Treatment (clinicaltrials.gov) - P3 | N=387 | Recruiting | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Recruiting | N=285 ➔ 387 | Trial completion date: Mar 2023 ➔ Jun 2023

Enrollment change • Enrollment open • Trial completion date • Pain

A Clinical Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of HSK21542 Injection in Liver Disease Subjects With Pruritus (clinicaltrials.gov) - P2 | N=90 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Completed | Trial completion date: Nov 2022 ➔ Aug 2022

Trial completion • Trial completion date • Dermatology • Hepatology • Pruritus

A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of HSK21542 Injection in Subjects Undergoing Hemodialysis (clinicaltrials.gov) - P2 | N=131 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Recruiting ➔ Completed

Trial completion • Dermatology • Pruritus • Renal Disease • CRP • IL6

A Clinical Study to Evaluate Efficacy and Safety of HSK21542 for Postoperative Analgesia of Subjects Undergoing Elective Laparoscopic Surgery Under General Anesthesia (clinicaltrials.gov) - P3 | N=276 | Completed | Sponsor: Haisco Pharmaceutical Group Co., Ltd. | Not yet recruiting ➔ Completed

Trial completion • Anesthesia