What question did this study set out to answer?

To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of JMKX003142 in healthy Chinese subjects.

March 7, 2026Open Access

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Administration JMKX003142 in Chinese Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Single, and Multiple Ascending Dose Phase I Clinical Trial

Puntos clave

To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of JMKX003142 in healthy Chinese subjects.
Randomized, double-blind, placebo-controlled design
48 subjects received single ascending doses of JMKX003142
30 subjects received multiple ascending doses of JMKX003142 for five days
Primary endpoint focused on safety and tolerability, secondary on PK and PD profiles
JMKX003142 injection showed favorable safety and tolerability with only mild adverse events
C max and AUC increased proportionally with higher doses
Mean terminal half-life of JMKX003142 ranged between 5.2 and 12.7 hours post single injection
Significant diuretic effect observed at doses of 1 mg and above

Resumen

Purpose: This study is the first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of single ascending doses (SAD) and multiple ascending doses (MAD) of JMKX003142 injection in healthy Chinese subjects. Patients and Methods: In this Phase I, randomized, double-blind, placebo-controlled study, 48 subjects in the SAD (0.1– 6 mg) study received intravenous injection of JMKX003142 or placebo in ascending dose. Thirty subjects in the MAD (1– 4 mg) study received an intravenous injection of JMKX003142 or placebo once a day for five consecutive days. The primary endpoint was the safety and tolerability of JMKX003142 injection, with the secondary and exploratory endpoints focusing on its PK and PD profiles, respectively. Results: The JMKX003142 injection exhibited favourable safety and tolerability, with all treatment-emergent adverse events (TEAEs) being mild. No serious adverse events, deaths or discontinuations due to TEAEs were observed. Following single and multiple intravenous injections of JMKX003142, the maximum concentration (C max ) and area under plasma concentration–time curve (AUC) of JMKX003142 and its metabolites increased with dose level, with increases in C max being dose-proportional. In 1 mg or higher dose group of SAD study, the mean terminal half-life (t 1/2 ) of JMKX003142 was between 5.2 and 12.7 h. Following multiple intravenous injections of JMKX003142, the t 1/2 of JMKX003142 was determined to range from 11.1 and 11.8 h. Moreover, JMKX003142 demonstrated favourable PD profiles following both single and multiple intravenous injections. The evaluation of the daily cumulative urine volume indicated that the diuretic effect of the JMKX003142 injection was evident at doses of 1 mg and above, with effects intensifying at higher doses. Conclusion: Overall, both single and multiple intravenous injections of JMKX003142 have been demonstrated to be safe, well tolerated, and to possess excellent PK characteristics as well as significant diuretic activity. Trial Registration: This study was registered with ClinicalTrials.gov (NCT06344533). Keywords: active arginine vasopressin V 2 receptor antagonist, JMKX003142, safety, tolerability, pharmacokinetics, pharmacodynamics

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Cite This Study

Cui et al. (Sun,) studied this question.

synapsesocial.com/papers/69abc1235af8044f7a4e9c49 https://doi.org/https://doi.org/10.2147/dddt.s583445

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