The drug cligosiban, a selective oxytocin receptor antagonist (OTR) being developed for the treatment of premature ejaculation (PE) is safe and well-tolerated in healthy men, according to two recent Journal of Sexual Medicine papers.
“[T]he pharmacokinetic and toleration profiles of cligosiban make it a promising candidate for the treatment of PE and support its further evaluation in Phase II efficacy studies,” the authors reported in January.
Men with PE ejaculate before they wish to. They often feel no control over when they climax, leading to great personal distress and, in some cases, relationship conflict.
Published online in October 2018, the first paper investigated the pharmacokinetics, safety, and tolerability in single doses of cligosiban. The authors discussed three separate studies that took place between October 2017 and December 2016. Overall, these studies involved healthy men between the ages of 18 and 45 in Europe and North America.
The men received single cligosiban doses ranging from 0.3 mg to 2,400 mg. Cligosiban was administered as aqueous solutions or dispersions, capsules, and caplets. Some men received their doses after fasting and some had eaten before their dose.
The researchers analyzed blood and urine samples for each man and made safety assessments, taking note of adverse events. One subgroup of men provided samples of cerebrospinal fluid (CSF).
Overall, the researchers determined that in healthy men, cligosiban was safe and well tolerated at doses up to 2,400 mg. Both solid and liquid forms were “rapidly absorbed” after fasting (between one to three hours). Absorption was slower when men took cligosiban with food.
Based on CSF sample analysis, the researchers determined that cligosiban does penetrate the central nervous system.
Reported adverse events included headache, insomnia, back pain, and lightheadedness. One participant had a faster heart rate, and another had mild palpitations.
The second paper, published online in January 2019, looked at similar parameters in men taking multiple doses of cligosiban.
Researchers conducted two studies, involving a total of 72 men aged 18 to 45, between November 2013 and July 2016 in the United Kingdom. Participants received cligosiban in doses ranging from 100 mg to 2,400 mg once a day for 10 days. Some men were given a placebo. All doses were given as aqueous dispersions.
Assessments were similar to those in the first paper, except semen samples were collected from one group of men on the 9th day of treatment.
Cligosiban was rapidly absorbed and well tolerated at all doses. The adverse event rate was low. Two participants withdrew from the trial because of hives and a rash.
Minimal amounts of cligosiban were found in the men’s ejaculate “and would not be expected to be of any clinical relevance to the partner,” the authors wrote, adding “couples using cligosiban should not require a barrier method unless this is part of the couple’s contraceptive measures.”
The drug is “associated with an appropriate pharmacokinetic profile appropriate for an as-required or once-daily dosing regimen,” the authors concluded.
Resources
The Journal of Sexual Medicine
Muirhead, Gary J., BSc (Hons), FIMLS, et al.
“Pharmacokinetics, Safety, and Tolerability of Multiple Doses of the Novel Oxytocin Receptor Antagonist Cligosiban in Development for Premature Ejaculation: Two Randomized Clinical Trials in Healthy Subjects”
(Full-text. Published online: January 4, 2019)
https://www.jsm.jsexmed.org/article/S1743-6095(18)31327-4/fulltext
Osterloh, Ian H., MRCP, et al.
“Pharmacokinetics, Safety, and Tolerability of Single Oral Doses of a Novel Oxytocin Receptor Antagonist—Cligosiban—in Development for Premature Ejaculation: Three Randomized Clinical Trials in Healthy Subjects”
(Full-text. Published online: October 16, 2018)
https://www.jsm.jsexmed.org/article/S1743-6095(18)31169-X/fulltext