Novel Oral Testosterone Replacement Therapy Is Safe and Effective in Clinical Trials

Topical or depot formulations of testosterone replacement therapy (TRT), indicated for hypogonadal men with low serum testosterone levels, are associated with several potential impediments to proper and efficient use, including inadvertent testosterone transfer, messy application (for testosterone gels), poor long-term adherence/retention rates, and superphysiologic testosterone levels in some patients.

According to the authors of “Efficacy and Pharmacokinetics of LPCN 1021, a Novel Oral Testosterone Replacement Therapy (TRT), in Hypogonadal Men: Study of Androgen Replacement (SOAR),” presented at ENDO 2015, because of these factors there is a need for testosterone formulations “that are more user-friendly, limit blood level dose excursions and avoid testosterone transdermal transfer.”

Christina C. Wang, MD, professor in the Division of Endocrinology, Metabolism & Nutrition, Department of Medicine, Harbor-UCLA Medical Center & Los Angeles Biomedical Research Institute, presented results from the SOAR phase 3 trial involving LPCN 1021, a novel oral testosterone undecanoate formulation

SOAR is a randomized, active-controlled, 12-month, open-label, multicenter, dose-titration trial that included men age 18-80 with testosterone levels <300 ng/dL (measured on two separate days in the morning) who were diagnosed prior to age 65. Treatment-naïve patients and participants who received TRT patients after washout, were randomized to either oral LPCN 1021 (n=210) or to Androgel 1.62% (n=105).

Initial LPCN 1021 dose was 225 mg BID taken with a meal. The dose could be titrated up (eg, if testosterone C_ave,24h <300 mg/dL) or titrated down (eg, if testosterone C_max was >1500 mg/dL) at weeks 4 and 8 based on 24-hour pharmacokinetics (PK). Researchers assessed efficacy at week 13 based on testosterone C_ave,24h from serum samples. Safety assessment was continued out to 52 weeks.

Wang and her colleagues observed that “LPCN 1021 reliably restored and maintained testosterone levels in the eugonadal range (300-1140 ng/dL) in 88.2% of hypogonadal men. Mean (SD) testosterone C_ave,24h was 447 (166) ng/dL, consistent with other non-oral TRT therapies.”

The researchers noted there was no significant dose timing effect, suggesting consistent intra-day performance. Overall variability was low (37% CV for C_ave,24h); 82.9% of subjects had peak serum testosterone (C_max) <1500ng/dL, less than 5% had C_max 1800-2500 ng/dL, and 2% had serum testosterone levels >2500 ng/dL. The authors described the cases in the last group as “sporadic, transient, and isolated, with no associated clinical events.” Eighty-five percent of subjects required one or fewer dose adjustments, suggesting “a safe and effective titration algorithm.” No serious adverse events were reported during the study.

Based on these findings, the authors concluded that LPCN 1021 is associated with “acceptable C_ave and C_max excursions, consistent with US FDA required targets met by other non-oral TRT products.” Several characteristics of LPCN 1021 may improve patient adherence compared to topical, transdermal, injectable, or implanted TRT products.

After the presentation, one questioner remarked that it is difficult to titrate dosage in regular clinical practice and asked if there is a clinical plan for administration of the product during routine practice, including a recommended interval for sampling for testosterone.

Wang said she was an investigator and could not speak for the sponsor (Lipocine). She said that when the clinical trials are concluded, the PK data will have to be evaluated to determine the optimal time for administration and monitoring. She also noted that the ambulatory effects on testosterone sampling had to be taken into consideration.