Conference Coverage

Novel oral testosterone undecanoate under FDA review




CHICAGO – A unique investigational oral testosterone replacement product for hypogonadal men showed efficacy and safety comparable to a commercially available testosterone gel in two phase III clinical trials, which drew considerable interest when presented at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

This formulation of oral testosterone undecanoate, known as Rextoro, uses proprietary self-emulsifying technology to provide more consistent absorption and a longer half-life than oral testosterone undecanoate products long available outside the United States.

The new product fulfills an unmet need for an effective and convenient treatment for male hypogonadism that avoids the risk of unintended testosterone transference to women and children inherent in currently marketed topical testosterone products, said lead investigator Dr. Ronald S. Swerdloff, professor of medicine at the University of California, Los Angeles, and chief of the division of endocrinology at Harbor-UCLA Medical Center.

"An oral testosterone replacement therapy would be the preferred choice for many hypogonal men," he said.

Clarus Therapeutics filed for marketing approval for Rextoro with the Food and Drug Administration earlier this year on the strength of the two phase III studies. In addition, the company is sponsoring a supplemental phase IV, open-label, 12-month safety study to be reported later this summer.

The phase IV study is being conducted to resolve safety questions raised in one of the two phase III studies presented at ICE/ENDO 2014. In this 325-patient, open-label, 12-month multicenter trial in which patients were randomized to the investigational oral testosterone or to 1% AndroGel, the oral therapy group experienced a 22% reduction from baseline in HDL, compared with a 12% decrease with the testosterone gel. In addition, two patients in the oral testosterone group had an acute MI; none did in the topical therapy group. Hematocrit levels rose by 3% in oral testosterone–treated patients, although mean values remained within the normal range.

LDL and total cholesterol, triglyceride, C-reactive protein, lipoprotein-associated phospholipase A2, and prostate-specific antigen levels did not differ between the two treatment groups.

Moreover, in the second and pivotal phase III trial, which utilized a revised Rextoro dose-titration algorithm, the reduction in HDL over the course of 114 days of treatment was a more modest 9%. This second trial was a single-arm study involving 144 Rextoro-treated patients.

The revised dose-adjustment algorithm involved starting treatment at 200 mg of oral Rextoro twice daily, then measuring serum testosterone 3-5 hours after the morning dose on days 30 and 72. A value outside the range of 200-750 ng/dL triggered a 50-mg increase or decrease. When this algorithm was used, 75% of treated patients were maintained within the target eugonadal range, compared with 84% of the oral testosterone group and 79% of the testosterone gel–treated patients in the first phase III trial. Under the revised algorithm, only 3% of patients experienced a transient serum peak testosterone excursion greater than 2,500 ng/dL, Dr. Swedloff reported.

The phase III trials were funded by Clarus. Dr. Swerdloff is a consultant to Clarus and Endo Pharmaceuticals.

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