Clinical Trial Tested Safety of Potential New Drug to Manage Endometriosis

The drug candidate of a non-peptide gonadotropin-releasing hormone (GnRH) antagonist had a good safety profile in clinical trial.

Key Points

Highlights: 

• The safety, pharmacokinetics, and pharmacodynamics of SHR7280, a non-peptide gonadotropin-releasing hormone antagonist, are favorable in a phase 1 clinical trial.

Importance:

• SHR7280 could be further developed as a potential drug to manage endometriosis symptoms.

What’s done here:

• Researchers conducted a phase 1 clinical trial in 30 premenopausal women with endometriosis using 3 different doses of SHR7280 to test the safety, pharmacokinetics, and pharmacodynamics of the drug. 

Key results:

• The treatment was well-tolerated.
• Seventy-nine% of women receiving the drug and 83% of those receiving placebo reported adverse events,  there were no severe adverse events.
• SHR7280 was rapidly absorbed and the plasma concentration was dose-dependent.
• SHR7280 could effectively suppress both estradiol and luteinizing hormone and prevent progesterone increase in a dose-dependent manner. 

Lay Summary

The non-peptide gonadotropin-releasing hormone antagonist SHR7280 has favorable safety, pharmacokinetics, and pharmacodynamics in 3 different doses, according to the results of a phase 1 clinical trial published in the scientific journal Clinical Pharmacokinetics.

“The results of this study provide evidence to support the further development of SHR7280 as a gonadotropin-releasing hormone antagonist for the treatment of endometriosis-related pain in the subsequent Phase 2 trial,” wrote the authors of the study.

In the phase 1 portion of the trial, 24 premenopausal women received SHR7280 while 6 received a placebo for 21 consecutive days. The treatment dose started from 200 mg daily and then increased to 300 mg daily and 200 mg twice a day, and the results showed that the drug was well tolerated. 

A total of 79% of the patients and 83% of those who received the placebo reported adverse events, most of these were mild. 

The mean half-life at steady state was 6.9 hours for the 200 mg-a-day dose, 7.4 hours for the 300 mg-a-day dose, and 2.8 hours for the 200 mg twice-a-day dose. There was little or no accumulation observed. 

Pharmacodynamic analysis showed that the drug could effectively suppress the concentration of estradiol and luteinizing hormone and prevent progesterone increase in a dose-dependent manner within the desired therapeutic window, throughout the treatment period.

Research Source: https://pubmed.ncbi.nlm.nih.gov/37838623/