Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of KR25102 in Healthy Volunteers

Официальное название

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Characteristics of Single and Multiple Ascending Intravenous Doses of KR25102 for Injection in Healthy Adult Chinese Participants

Обзор

Phase 1 Single Ascending Doses(SAD): Six cohorts of 53 healthy volunteers (HVs) will receive a single IV bolus injection of study drug or placebo. Phase 1 Multiple Ascending Doses(MAD): Three cohorts of 30 HVs will receive multiple IV bolus injections of study drug or placebo every day. After 7 days of continuous administration, the safety, tolerance and Pharmacokinetic/Pharmacodynamic characteristics of multiple administrations were evaluated.

Подробное описание

This study adopts a single-center, randomized, double-blind, placebo-controlled parallel-group, dose-escalation design.

This single ascending dose (SAD) study is designed with six dose cohorts: 5 mg, 10 mg, 20 mg, 30 mg, 45 mg, and 60 mg. A total of 53 healthy adult participants are planned to be enrolled.

Three participants are planned for the 5 mg cohort, randomized in a 2:1 ratio of investigational product to placebo. Each of the remaining five dose cohorts will enroll 10 participants, randomized in an 8:2 ratio of investigational product to placebo.

For the multiple ascending dose (MAD) part, three dose cohorts (10 mg, 20 mg, and 30 mg) are planned. A total of 30 healthy adult participants will be enrolled, with 10 participants per cohort randomized in an 8:2 ratio of investigational product to placebo.Subjects will receive once daily administration for 7 consecutive days according to the randomization scheme.

Вмешательства

• Препарат KR25102 for Injection
  Intravenous injection of KR25102 for Injection at different dose levels in SAD and MAD cohorts.
• Препарат Placebo for KR25102 for Injection
  Intravenous injection of matching placebo.

Первичные конечные точки

• Incidence and Severity of Adverse Events (AEs) [Срок оценки: From study drug administration to 15 days after the last dose]

Вторичные конечные точки (12)

• Single-Dose Pharmacokinetic (PK) Parameters [Срок оценки: From study drug administration to 120 hours after single dose administration]
• Single-Dose Pharmacokinetic (PK) Parameters [Срок оценки: From study drug administration to 120 hours after single dose administration]
• Single-Dose Pharmacokinetic (PK) Parameters [Срок оценки: From study drug administration to 120 hours after single dose administration]
• Single-Dose Pharmacokinetic (PK) Parameters [Срок оценки: From study drug administration to 120 hours after single dose administration]
• Single-Dose Pharmacokinetic (PK) Parameters [Срок оценки: From study drug administration to 120 hours after single dose administration]
• Single-Dose Pharmacokinetic (PK) Parameters [Срок оценки: From study drug administration to 120 hours after single dose administration]
• Multiple-dose Pharmacokinetic (PK) Parameters [Срок оценки: From multiple-dose administration to 120 hours after the 7th dose]
• Multiple-dose Pharmacokinetic (PK) Parameters [Срок оценки: From multiple-dose administration to 120 hours after the 7th dose]
• Multiple-dose Pharmacokinetic (PK) Parameters [Срок оценки: From multiple-dose administration to 120 hours after the 7th dose]
• Multiple-dose Pharmacokinetic (PK) Parameters [Срок оценки: From multiple-dose administration to 120 hours after the 7th dose]
• Multiple-dose Pharmacokinetic (PK) Parameters [Срок оценки: From multiple-dose administration to 120 hours after the 7th dose]
• Multiple-dose Pharmacokinetic (PK) Parameters [Срок оценки: From multiple-dose administration to 120 hours after the 7th dose]

Критерии участия

Критерии включения

• Male and female participants aged between 18 and 55 years inclusive (as of the time of signing the informed consent form);
• Male participants with body weight ≥ 50 kg and female participants with body weight ≥ 45 kg, with a body mass index (BMI) ranging from 19 to 26 kg/m² (inclusive of boundary values);
• Participants and their partners have no plans for conception, sperm donation or oocyte donation from signing the informed consent form until 2 months after the last dose of study drug, and are willing to adopt highly effective contraceptive measures;
• Female participants: not pregnant or breastfeeding; female participants of child-bearing potential must have negative serum pregnancy test results at screening and baseline visits;
• For groups requiring pain testing: willing to undergo pain tests and pass training; with no wounds or skin diseases on the skin at the pain-stimulated site;
• Participants fully understand the purpose, requirements and potential risks of this trial, are willing to strictly comply with all trial requirements, voluntarily participate in the clinical trial and sign the written informed consent form.

Критерии исключения

• Subjects with previous or current clinical acute or chronic diseases including but not limited to cardiovascular, endocrine-metabolic, neuropsychiatric, digestive, respiratory, hematopoietic-lymphoid, immune, urinary, musculoskeletal diseases and malignant tumors, who are judged unsuitable for enrollment by the investigator;
• Subjects with personal or family history of hereditary angioedema;
• Subjects who have undergone major surgery within 6 months prior to screening, or plan to receive surgical operations during the trial;
• Subjects who have taken any medicines or health supplements (including Chinese herbal medicines) within 14 days before dosing; or those who are known to require other drug treatments during the trial at screening.
• Subjects who have used any hepatic enzyme inhibitors/inducers within 1 month before dosing (inhibitors such as itraconazole, clarithromycin, ketoconazole, ritonavir, nelfinavir, cobicistat, telithromycin or nefazodone; inducers such as carbamazepine, phenytoin, phenobarbital, St. John's wort, etc.).
• Subjects who have participated in any clinical trials with investigational drugs/devices within 3 months prior to screening, or plan to participate in other clinical trials during the study.
• Subjects with a history of drug abuse or positive results in drug abuse screening;
• Subjects with clinically significant abnormal physical examination results at screening or baseline as judged by the investigator;
• Subjects with positive screening results for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody or treponema pallidum antibody;
• Subjects with cardiac diseases including but not limited to congenital long QT syndrome, torsades de pointes or risk factors for torsades de pointes (e.g., cardiac insufficiency, family history of long QT syndrome), those currently receiving Class IA anti-arrhythmic drugs (e.g., quinidine or procainamide), Class III anti-arrhythmic drugs (e.g., amiodarone or sotalol) or other drugs known to affect QT interval, or those with Fridericia-corrected QT interval (QTcF) ≥ 450 ms (male), QTcF ≥ 460 ms (female), PR interval > 200 ms or QRS interval ≥ 120 ms at screening;
• Subjects who fail pain test training as judged by the investigator (only applicable to groups requiring pain testing).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Китай · 1 центр

• The Third Xiangya Hospital, Central South University — Чанша

Идентификаторы

NCT: NCT07618156 · KR25102-202601

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗