Phase I dose-escalation trial of intravaginal curcumin in women for cervical dysplasia
Open Access J Clin Trials.2017; 9: 1–10.
Cervical neoplasia (also termed as cervical dysplasia), is the anomalous growth of cells on the surface of the cervix. The growth of the cells could potentially lead to cervical cancer. Curcuminoids have been shown to hinder the propagation of various cancerous cells in vitro. Curcuminoids have been shown to inhibit various cervical cancer cell lines in preclinical observations. Intravaginal administration is the method of drug administration for pathological conditions such as cervical neoplasia. Tolerability for the drug is vital factor for the drug in such an administration. Curcuminoids were tested for the tolerable maximum dose in healthy female subjects.
To assess the safety, tolerability, and pharmacokinetics of intravaginal curcumin in healthy women. This is a Phase I trial demonstrating safety and tolerability of intravaginal curcumin for future use in women with cervical neoplasia.
It was a 3+3 dose-escalation Phase I trial in a group of women aged 18-45 years. Thirteen subjects were given one of four doses of curcumin powder (500 mg, 1,000 mg, 1,500 mg, and 2,000 mg) packed in gelatin capsules, which was administered intravaginally daily for 14 days. The primary end point for this study was safety based on severe adverse events regarding laboratory toxicity, clinical findings, and colposcopic abnormalities.
- No dose-limiting toxicities (0/13) were experienced (95% confidence interval: 0.0%-22.8%) in this study
- The pharmacokinetics data demonstrated that curcumin and curcumin conjugates were not measurable in the serum and negligible in the urine of the study participants
- Although 23 adverse events occurred during the course of the trial, all events were grade I based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and were resolved by the end of the study in an average of 9 days
- Fifty-six percent of the adverse events were related to the study drug, which included genital pruritus (23% of subjects), vaginal discharge (100%), vaginal dryness (15%), abnormal prothrombin (23%), and hypokalemia (8%)
Intravaginal curcumin was well tolerated by all subjects and safe. There was no evidence of systemic absorption or significant local absorption of intravaginally administered curcumin.