Repros Therapeutics公司（NasdaqCM：RPRX）宣布Proellex经阴道给药的两个动物模型试验已经完成，研究表明Proellex经阴道给药对孕激素敏感组织的效果与该公司以前开发的口服最高剂量相当。最重要的是，可从动物实验的药物暴露数据推算人类的暴露剂量，Proellex经阴道给药可达到的最高循环浓度是其人体50 mg剂量时的大约2%，而仅是以前的人体试验中最低口服剂量12.5 mg的6.5％。

如果开展Proellex经阴道给药的研究项目在2011年第二季度的获得FDA同意，就可以在明年年底比较低剂量口服用药和经阴道给药的效果。

在3期研究中，该药首次被吸收和肝脏处理后的高浓度活性成分和初级代谢产物使约3-4%应用50 mg Proellex的妇女产生迟发性毒性反应。12.5 mg Proellex肝脏毒副作用与安慰剂组相同。12.5 mg给药剂量的最高胃肠外和代谢物浓度为50 mg的25%。

第一个动物研究是以狗为动物模型对Repros研究中的阴道制剂和口服制剂进行比较。在给药剂量相同时，经阴道给药后活性成分和代谢产物的最高循环浓度是口服给药的6.5％。

为确定这些低的循环浓度是否对预期疗效有影响，该公司以兔子为实验对象进行了研究。研究数据表明，相同剂量Proellex经阴道给药的活性为口服给药的4倍。这一结果与对狗进行研究的结果耦合，表明或可开发Proellex更安全有效的剂型。该公司正在完成一项剂量优化研究（以兔为模型），并在向FDA申请预pre-IND会议前，期待这些研究结果指导阴道刺激研究。该公司计划表其研究查结果。涵盖这一技术的专利申请悬而未决，该制剂使用的标准配药辅料先前已被证明没有刺激阴道的特点。

Proellex®

Proellex®, is an orally active, small molecule, selective blocker of the progesterone receptor that we believe may be developed for uterine fibroids and endometriosis.

On June 10, 2010, the Food and Drug Administration (FDA) notified Repros that the full clinical hold for the Company's Proellex Investigational New drug Applications (INDs) was lifted to partial clinical hold status. The Company will be allowed to run a single study under the new partial clinical hold status. The new low dose study is designed to explore both safety and signals of efficacy in an escalating dose fashion.

The new study will test 5 different doses of Proellex (1, 3, 6, 9 and 12 mg) with 1 mg being the first dose tested. Each dose will be compared to placebo with weekly assessments of liver function during both the placebo and drug period. Higher doses will not be studied until the Company is confident that it is safe to proceed to the next dose and has reported the safety findings to the FDA. Subjects will be dosed with the active drug for 10 weeks, which will allow for adequate time to determine the impact of a given dose on trends in liver function. Each dose will be tested in 12 different subjects and assessment of pharmacokinetic parameters will be obtained at start of dosing and end of the dosing period to determine overall and maximum drug exposure for a given dose. The Company will also monitor changes in menstrual bleeding patterns and ovulation as well as changes in endometrial thickness. The FDA requires that an independent Drug Safety Monitoring Board be established and that the “Informed Consent” clearly state the liver toxicity previously experienced with Proellex. The Company believes the toxicity experienced was dose dependent and that the lower doses being tested now are outside the range where toxicity was previously seen.

It should be noted elevations listed as greater than a specific value are a subset of the next lowest value group (nested). In general, a trend is seen with increasing dose that is indicative of an increased frequency and severity of liver toxicity. At a dose of 12.5 mg the frequency and severity of liver enzyme excursions is similar to the control group based on the limited data available.

In a 120 patient study of Proellex as a treatment of uterine fibroids conducted in the United States (roughly 40 subjects per arm) both a 12.5 and 25 mg dose of Proellex were compared to placebo. In this study both the 12.5 and 25 mg doses achieved highly statistically significant results when compared to placebo when menstrual bleeding was assessed (p< 0.0001). The two doses also achieved highly statistically significant improvement in quality of life measures using the Uterine Fibroid Symptom Quality of Life questionnaire developed and validated by Georgetown University and used in the development of device like treatments of uterine fibroids such as uterine artery embolization. There was no statistical difference in efficacy measures between the two doses. Importantly in the Phase II US trial a significant percentage of women stopped menstruating. Over 80% of women on both the 12.5 and 25 mg doses exhibited no menses during the three month trial whereas all women on placebo exhibited at least one menses. The Company believes that the evaluation of ovulation and menstrual bleeding patterns in the low dose trial will provide strong evidence for efficacy warranting further development.

The Company plans to proceed with the manufacture of the lower doses of Proellex capsules and hopes to begin dosing subjects this summer. Though the new study is more complex than that originally submitted to the FDA, the Company believes it can complete the trial within roughly 18 months after first dose. Presuming a safe and effective dose is identified and the FDA is in agreement, Repros anticipates that it will be able to proceed with large efficacy trials for both uterine fibroids and endometriosis, subject to available funds, or outlicense of the product to a major pharmaceutical company.