ZY5301 tablet effective for chronic pelvic pain

ZY5301 tablet effective for chronic pelvic pain | Image Credit: © valiantsin- stock.adobe.com.

The ZY5301 tablet is effective for treating chronic pelvic pain (CPP) caused by pelvic inflammatory disease (PID) in women, according to a recent study published in JAMA Network Open.

PID commonly presents in reproductive-aged women as infection-induced inflammation of the upper genital tract. Approximately 1 million US women experience PID annually, with a PID diagnosis reported in approximately 2.5 million reproductive-aged women.

The risk of severe sequelae of PID increases from inadequate treatment. Subsequent infertility is reported in 10% to 20% of PID cases and CPP in 40%. CPP is associated with reduced physical function, general health, vitality, social functioning, and mental health.

ZY5301, a part preparation extracted from A decumbens Thunb, has been linked to reduced uterine swelling caused by PID in rats. However, human trials are necessary.

To evaluate the safety and efficacy of ZY5301 in women with CPP caused by PID, investigators conducted a phase 2 randomized clinical trial in 9 centers in China. Participants included women aged 18 to 55 years meeting the clinical diagnostic criteria for PID and with at least 6 months of nonperiodic lower abdominal or pelvic pain.

Additional inclusion criteria included being sexually active, having visual analog scale (VAS) scores of 4 or more points before enrollment, McCormack scale scores from 4 to 12, willingness to use contraception, and no obvious pelvic pathology.

Patients with acute PID onset, pregnancy gynecologic tumor diagnosis, serum cancer antigen 125 over 1.5 times the upper limit of normal (ULN), or kidney function above the ULN were excluded. Participants were randomized 1:1:1 to receive placebo, ZY5301 300 mg/d, or ZY5301 600 mg/d. All groups took the medication 3 times per day for 12 weeks.

Evaluations occurred within 3 days before treatment, at treatment initiation, visit 1, day 28 ± 4, day 56 ± 4, day 84 ± 4, and during follow-up at 4 weeks ± 4 days. Safety assessments were also performed throughout the trial period.

Efficacy was determined using VAS scores. Pain intensity was measured on a 1 to 10 scale, with higher numbers indicating increased pain. The sum of each day’s score in a week was divided by the number of days to calculate the mean VAS score, with the mean VAS score at week 1 used as the baseline. A score of 0 to 1 was considered pain remission.

Outcome measures included changes in VAS mean scores from baseline to week 12, area under the VAS score-time curve, pain remission rate, and pain remission time. The Short Form-12 (SF-12) scale and McCormack scale were used to measure physical and mental health and gynecologic pain, respectively.

Finally, treatment-emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs) were assessed. Severity was determined based on Common Terminology Criteria for Adverse Events, version 5.0.

There were 180 participants included in the analysis, 60 in each group. Three patients were lost during follow-up, 2 in the ZY5301 600 mg/d group and 1 in the placebo group. Participants had a mean age of 37.4 years in the ZY5301 300 mg/d group, 37.1 years in the ZY5301 600 mg/d group, and 38.9 years in the placebo group.

At baseline, mean VAS scores in the ZY5301 300 mg/d group, ZY5301 600 mg/d group, and placebo group were 5 cm, 5.1 cm, and 5 cm, respectively. These scores changed by -3.5, -3.8, and -2.1, respectively, by week 12 of treatment.

Changes in the VAS score were significantly different between the ZY5301 groups and placebo, but not between the 2 ZY5301 groups. The mean areas under the VAS score-time curve significantly varied between the 3 groups, at 194.1 cm in the 600 mg/d group, 215.0 in the 300 mg/d group, and 282.4 in the placebo group.

Pain remission was reported in 11.9% of the placebo group, 43.3% of the 300 mg/d group, and 53.5% of the 600 mg/d group. The 600 mg/d group and 300 mg/d group also showed significant improvements in SF-12 and McCormack scores.

TEAEs were reported in 36.2% of the ZY5301 600 mg/d group, 38.3% of the ZY5301 300 mg/d group, and 28.8% of the placebo group. While some patients in each group also experienced TRAEs, these were ruled to be unrelated to the treatment.

These results indicated a significant reduction of CPP from 12 weeks of ZY5301 treatment. Investigators recommended a ZY5301 600 mg/d dose be investigated in a phase 3 trial.

Reference

Teng X, Li H, Yang D, et al. ZY5301 Tablet vs placebo for treatment of chronic pelvic pain after pelvic inflammatory disease: A phase 2 randomized clinical trial. JAMA Netw Open. 2024;7(7):e2423229. doi:10.1001/jamanetworkopen.2024.23229