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Background <p>SHR7280 is an oral small-molecule gonadotropin-releasing hormone (GnRH) antagonist that can be developed as therapeutic agent for the treatment of hormone-dependent pathologies, including prostate, breast, and ovarian cancers. SHR7280 dry suspension formulation is being developed to provide an alternative mode of administration for order patients, those using nutritional tubes, and those unable to swallow solid dosage forms.</p> Objective <p>This study evaluated the relative bioavailability, pharmacokinetics (PK), and safety of SHR7280 dry suspension and tablets administered in a single dose in healthy Chinese volunteers.</p> Methods <p>A randomized, open, two-preparation, two-sequence, two-cycle, double-crossover design was used in this study. The plasma drug concentration was determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The main PK parameters of the two formulations of SHR7280 were calculated by noncompartmental analysis using Phoenix WinNonlin (version 8.3.4) software. A total of 16 healthy participants were randomized to receive SHR7280 (200 mg) as tablets (<i>n</i> = 8) or dry suspension (<i>n</i> = 8) formulation.</p> Results <p>The geometric least squares mean ratio (90% confidence interval [CI]) for maximum concentration of drug in blood plasma (<i>C</i><sub>max</sub>) and area under the plasma concentration–time curve from time 0 to <i>t</i> (AUC<sub>0–<i>t</i></sub>) and from time 0 to infinity (AUC<sub>0–∞</sub>) between the dry suspension of SHR7280 and its tablets were calculated as follows: <i>C</i><sub>max</sub>—101.90% (90% CI 79.50–130.62), AUC<sub>0–<i>t</i></sub>—111.58% (90% CI 91.71–135.76), and AUC<sub>0–∞</sub>—111.44% (90% CI 91.70–135.43). A total of nine (56.3%) subjects experienced treatment-emergent adverse events (TEAEs).</p> Conclusions <p>The bioavailability of SHR7280 tablets was found to be comparable to that of dry suspension. The safety profile of two formulations was favorable. No serious adverse events or adverse drug reactions were reported.</p> Trial Registration <p>ClinicalTrials.gov (NCT05868057; 22 May 2023)</p>

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Relative Bioavailability of Single-Dose Oral Administration of Two SHR7280 Formulations (Dry Suspension and Tablets) in Healthy Chinese Volunteers

  • 期刊论文

  • 发表日期：

    2025年8月8日

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  • Xian Liu,
  • Ruzhai Qin,
  • Chang Shu,
  • Kai Shen,
  • Xi Li,
  • Lingyu Ma,
  • Xiaomei Li,
  • Lanping Li,
  • Jiao Peng,
  • Dongxiang Huang,
  • Sihan Chen,
  • Zhihong Xie,
  • Lika Ye,
  • Lian Duan

摘要

Background

SHR7280 is an oral small-molecule gonadotropin-releasing hormone (GnRH) antagonist that can be developed as therapeutic agent for the treatment of hormone-dependent pathologies, including prostate, breast, and ovarian cancers. SHR7280 dry suspension formulation is being developed to provide an alternative mode of administration for order patients, those using nutritional tubes, and those unable to swallow solid dosage forms.

Objective

This study evaluated the relative bioavailability, pharmacokinetics (PK), and safety of SHR7280 dry suspension and tablets administered in a single dose in healthy Chinese volunteers.

Methods

A randomized, open, two-preparation, two-sequence, two-cycle, double-crossover design was used in this study. The plasma drug concentration was determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The main PK parameters of the two formulations of SHR7280 were calculated by noncompartmental analysis using Phoenix WinNonlin (version 8.3.4) software. A total of 16 healthy participants were randomized to receive SHR7280 (200 mg) as tablets (n = 8) or dry suspension (n = 8) formulation.

Results

The geometric least squares mean ratio (90% confidence interval [CI]) for maximum concentration of drug in blood plasma (Cmax) and area under the plasma concentration–time curve from time 0 to t (AUC0–t) and from time 0 to infinity (AUC0–∞) between the dry suspension of SHR7280 and its tablets were calculated as follows: Cmax—101.90% (90% CI 79.50–130.62), AUC0–t—111.58% (90% CI 91.71–135.76), and AUC0–∞—111.44% (90% CI 91.70–135.43). A total of nine (56.3%) subjects experienced treatment-emergent adverse events (TEAEs).

Conclusions

The bioavailability of SHR7280 tablets was found to be comparable to that of dry suspension. The safety profile of two formulations was favorable. No serious adverse events or adverse drug reactions were reported.

Trial Registration

ClinicalTrials.gov (NCT05868057; 22 May 2023)