An institutional review board (IRB), also known as an independent ethics committee (IEC) or ethical review board (ERB), is a committee that has been formally designated to approve, monitor, and review biomedical and behavioral research involving humans with the aim to protect the rights and welfare of the research subjects. In the United States, the Food and Drug Administration (FDA) and Department of Health and Human Services (specifically Office for Human Research Protections) regulations have empowered IRBs to approve, require modifications in planned research prior to approval, or disapprove research. An IRB performs critical oversight functions for research conducted on human subjects that are scientific, ethical, and regulatory.

The National Research Act of 1974 defines IRBs and requires them for all research that receives funding, directly or indirectly, from what was the Department of Health, Education, and Welfare at the time, and is now the Department of Health and Human Services (HHS). IRBs are themselves regulated by the Office for Human Research Protections (OHRP) within HHS.

Repros Therapeutics’ new low dose study is designed to explore both safety and effectiveness in an escalating dose fashion. The study will test 5 different doses of Proellex (1, 3, 6, 9 and 12 mg) with 1 mg being the first dose tested. In previous studies a 12.5 mg dose was well tolerated and yielded statistically significant efficacy signals for both uterine fibroids and endometriosis.

The company plans to report the results after each patient dosing group has completed the 10-week dosing period. Based on previous work the  ompany anticipates that all five doses will be safe. Although the company believes that both the 1 and 3 mg dose will not yield any efficacy signal due to the low levels of projected absorbed drug, those doses were required by the FDA to assure patient safety at higher doses in light of the liver toxicity exhibited at 50 mg. Retros Therapeutics believes that roughly 80% of women at the 12 mg dose will exhibit changes in menstrual patterns that translate to clinical benefit for both uterine fibroids and endometriosis. The benefits expected are significant reduction in menstrual bleeding and reduction in menstrual pelvic pain. Since the Company does not have human experience at doses lower than 12.5 mg it is difficult to project what efficacy signal might be observed below 12 mg.

In addition to healthy volunteers the protocol allows for the recruitment of women with uterine fibroids, endometriosis, heavy menstrual bleeding or menstrual pelvic pain as these women should see benefit at an effective dose. Previously a dose of 12.5 mg Proellex achieved highly statistically significant results compared to placebo (p<0.0001) when assessing quality of life improvements and excessive menstrual bleeding in women with uterine fibroids. In a small study there was no statistical difference in reduction in pain scores in women with endometriosis when Proellex was compared to Lupron(R). Unlike Lupron, Proellex caused no change in markers of bone mineral density, a side effect which limits the duration that a woman can take Lupron, according to a statement issued by Retros Therapeutics. The company expects to commence dosing of the 1 mg cohort in August or early September. The Company believes it can have reportable data from the 12 mg group within roughly 18 months after starting the 1 mg subject group.