# FDA getting closer to approving Testosterone booster Androxal



## Arnold (Dec 24, 2010)

*FDA getting closer to approving Testosterone booster Androxal *(Enclomiphene Citrate)

Repros Therapeutics Inc today announced it has submitted to the FDA data collected from three different studies which the Company believes demonstrates that the assessment of testosterone levels between 8 and 10 in the morning is indicative of the maximum and average levels of the male hormone achieved during a particular day following the administration of Androxal®. In the Type B meeting held on November 8, 2010, and reported in the Company???s press release of November 9, 2010, the FDA stated the preferred method to determine testosterone levels in treatments designed to replace the hormone is a 24 hour assessment.

Repros used the services of an outside statistician, Dr. Richard Trout, Professor Emeritus, Rutgers University, in arriving at the conclusions it has reached.

The Company has conducted three trials in which serial testosterone measurements were made over a 24 hour period. Two of the studies assessed 14 (ZA-002) and 11 (ZA-003 subset) time points over the 24 hour period in a total of 28 subjects. A third study (ZN-018) obtained measurements at six points in a total of 20 subjects.

Using the data from the 002 and 003 studies the sponsor has determined that a single total testosterone assessment made between 8 and 10 in the morning correlates to the average of the values of the testosterone measurements for a given subject on a given day (correlation coefficient roughly 0.9 for the times 8, 9 and 10, p value < 0.001).

Performing the same assessment for the maximum value of total testosterone recorded in a 24 hour period, the same single total testosterone assessment made between 8 and 10 in the morning correlates to the maximum value of testosterone for a given subject on a given day (correlation coefficient roughly 0.9 for the times 8, 9 and 10, p value < 0.001).

From the 018 study that assessed men at baseline and after 14 days of treatment, the Company observed that Androxal raises each time point testosterone level by an average of 200 ng/dl at 12.5 mg and 260 ng/dl at a 25 mg dose.

Unlike topical testosterone preparations, Androxal maintains the normal daily rhythm of testicular testosterone production with peak levels generally occurring in the morning and trough levels exhibited in the evening. The testosterone levels achieved by the administration of topical preparations are a function of a variety of factors none of which relate to the normal daily rhythm. In some instances, subject to subject variability can lead to supernormal levels of testosterone several hours after administration of the topical preparations. The Company has committed to conduct one additional 24 hour study to show that Androxal???s action in maintaining the normal rhythm is both predictable and dose dependent.


----------



## Glycomann (Dec 29, 2010)

Update

December 28, 2010 09:30 AM Eastern Time 
Reanalysis by Outside Statistician Shows Androxal® Provides Statistically Significant Improvement in Testosterone Levels in Men with Male Hormone Levels ≤ 250 ng/dL

FDA recommends men with morning testosterone ≤ 250 ng/dl should be studied in Phase IIb trial

THE WOODLANDS, Texas--(BUSINESS WIRE)--Repros Therapeutics Inc.® (NasdaqCM:RPRX) today reported it has submitted to the FDA a reanalysis of the previously completed 200 subject trial ZA-003 of Androxal® in the treatment of secondary hypogonadism as noted by Repros in the Company’s press release of November 9, 2010. The Company contracted an outside statistician, Tony Orlando, Ph.D., V.P., Global Data Division, Pharm-Olam International Ltd., to conduct the analysis.

    “We believe Dr. Orlando’s observations bode well for our upcoming Phase IIb study and further reinforce the findings from our previous studies.”

Dr. Orlando performed several different analyses. He first assessed the subset of men in the 003 study that exhibited morning testosterone levels ≤ 250 ng/dl to mimic the upcoming Phase IIb study. He examined the data for the men after three months of treatment and again for those that completed the six month study. There were 11, 16, 20 and 21 men in the 12.5 mg Androxal, 25 mg Androxal, Androgel and placebo groups, respectively, that met the baseline testosterone criteria and completed three months of the study. After three months of treatment the mean change from baseline in morning testosterone levels for the four groups were 216.8, 260.5, 213.6 and 50.1 ng/dl for the 12.5 mg Androxal, 25 mg Androxal, Androgel and placebo groups, respectively. Even with the small number of men in this subset, both doses of Androxal achieved statistically significant changes from baseline results when compared to placebo (p=0.0001 @ 25 mg and 0.0021 @ 12.5 mg). For the men from this group that remained in the study for the full six month period, changes from baseline levels as compared to placebo remained significant (p<0.01).

Dr. Orlando also performed a “completer” analysis for all the men in the study. Now with roughly 33 to 37 men per group, he observed that mean changes of morning testosterone for the four groups from baseline to after six months of treatment were 139.4, 271.5, 132.3 and 12.5 ng/dl for the 12.5 mg Androxal, 25 mg Androxal, Androgel and placebo groups respectively. Both of the Androxal groups exhibited p values < 0.0001 compared to placebo. Mean testosterone levels after the six month study were 410.4 at 12.5 mg and 519.3 at 25 mg Androxal.

As part of Dr. Orlando’s analyses he also looked at the impact of Androxal and Androgel on luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the men with baseline morning testosterone ≤ 250 ng/dl. Androxal significantly increased LH levels in a dose dependent manner. LH stimulates the testes to produce testosterone. Androxal also significantly increased FSH in a dose dependent manner. FSH stimulates the testes to produce sperm. He further determined that there was a statistically significant correlation between changes in LH and changes in morning testosterone level (correlation = 0.6137, p value <0.0001). This analysis underscores the mode of action of Androxal which restores pituitary responsiveness to low circulating levels of testosterone, in turn stimulating the testes to produce normal levels of testosterone in a normal rhythmic pattern.

Conversely, Androgel significantly reduced pituitary secretions of both LH and FSH which further suppressed testicular function, and causes variability in testosterone levels not corresponding to the normal rhythmic pattern observed in healthy males.

One of the safety assessments proposed by the FDA that will be made in the planned Phase IIb study is to assess the impact of Androxal compared to placebo and Testim (an approved topical testosterone preparation) upon the reproductive status of men receiving three months of treatment with the study drugs. Dr. Orlando also observed that over 62% of men on Androgel in the analysis of the 003 study exhibited FSH levels below the lower limit of normal (1.4 mIU/ml) after three months of Androgel treatment, and noted that over 43% of those men had FSH levels below the lower limit of detection 0.3 mIU/ml. In a previous proof of principle study conducted by Repros it was found that roughly 80% of men with FSH levels less than 2.0 exhibited sperm parameters that would be considered sub fertile. After three months of treatment all men on the 25 mg dose of Androxal had FSH levels above 1.4 mIU/ml (minimum observed 2.9).

Joseph S. Podolski, President and CEO of Repros, commented, “We believe Dr. Orlando’s observations bode well for our upcoming Phase IIb study and further reinforce the findings from our previous studies.” He further stated, “Unlike testosterone replacement therapy, Androxal treats the underlying defect that is the reason for low testosterone levels in the majority of men that experience this condition. Androxal normalizes testicular function, improving testosterone levels back into the normal range, and maintains a man’s reproductive status.”

About Repros Therapeutics Inc.

Repros Therapeutics focuses on the development of oral small molecule drugs for major unmet medical needs that treat male and female reproductive disorders.


----------



## ~RaZr~ (Oct 30, 2011)

This does sound interesting, but I wonder how many "hoops" one would have to go through to be able to get a script? 

IMHO, with all the "hatred" towards testosterone and steroid, I think anyone trying to get a script for this would be looked over and watched very closely. Gotta love the government and it's priorities


----------



## spaemp3 (Nov 3, 2011)

JeremyTesta said:


> Just tried p-boost after reading some reviews about it. Worked good but pretty pricey. The trial was free but you have to pay for the shipping which was quick. Anyone know any coupon codes for p-boost.com?


 
SPAMMER get off the thread


----------

