A New Oral Testosterone Undecanoate Formulation Restores Testosterone to Normal Concentrations in Hypogonadal Men

Swerdloff, Ronald S.; Wang, Christina; White, William Β.; Kaminetsky, Jed; Gittelman, Marc; Longstreth, James; Dudley, Robert; Danoff, Theodore M.

doi:10.1210/clinem/dgaa238

Cited by 66 publications

(73 citation statements)

References 29 publications

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“… * These data were previously published. 20 C 3–5 , T concentration 3–5 h after morning dose; C 4 , T concentration 4 h after morning dose; C avg, average observed concentration over 24 h; CI, confidence interval; C max, maximum T concentration; PK, pharmacokinetics; T, testosterone. …”

Section: Resultsmentioning

confidence: 99%

“…Data published previously. 20 Cavg, average T concentrations; NaF-EDTA, sodium fluoride-ethylenediaminetetraacetic acid; PK, pharmacokinetics; SE, standard error; T, testosterone; TU, testosterone undecanoate.…”

Section: Patient Characteristics and Dispositionmentioning

confidence: 99%

“…PK simulation results evaluating mean T concentration (Cavg) versus time of single-sample collection [4 (C 4 ) or 3-5 (C 3-5 ) h after oral TU)] as surrogate for true Cavg * .Estimated % of patients with Cavg within target T interval (95% CI) on final PK visit These data were previously published 20. C 3-5 , T concentration 3-5 h after morning dose; C 4 , T concentration 4 h after morning dose; Cavg, average observed concentration over 24 h; CI, confidence interval; Cmax, maximum T concentration; PK, pharmacokinetics; T, testosterone.…”

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confidence: 99%

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A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men

Swerdloff

Dudley

2020

Therapeutic Advances in Urology

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Background: A novel formulation of oral testosterone undecanoate (TU) was studied in a long- and short-term phase III trial to evaluate safety and efficacy. Methods: Hypogonadal men (age 18–65 years; two morning serum testosterone (T) <300 ng/dl with signs/symptoms) were recruited into a 365 day (trial I) or 105 day (trial II), randomized, multicenter trial. Patients were randomized 1:1 to oral TU ( n = 161) or T-gel ( n = 160) in trial I, and 3:1 to oral TU, twice daily (BID) JATENZO® ( n = 166) or a topical T product [Axiron® ( n = 56)] in trial II. Dose adjustments were based on average T concentrations ( Cavg). Efficacy was assessed based on T levels, body composition and bone density. Safety was assessed by standard clinical measures. Results: Oral TU efficacy (% of patients with eugonadal T Cavg) was 84% (serum Cavg = 628 ± 343 ng/dl) and 87% (serum T equivalent Cavg ≈ 489 ± 155 ng/dl) in trials I and II, respectively. Oral TU significantly ( p <0.0001) improved all Psychosexual Daily Questionnaire parameters in trials I and II. In trial I, lean mass increased 3.2 ± 2.7 kg and fat decreased by 2.4 ± 3.6 kg (both p <0.0001) and bone density improved in hip (+0.012 ± 0.0225 g/cm2) and spine (+0.018 ± 0.0422 g/cm2) after 365 days (both p <0.0001). Oral TU-associated adverse effects were consistent with other T-replacement therapies but oral TU patients experienced a greater number of mild gastrointestinal adverse effects. Oral TU subjects in both studies exhibited an increase in mean systolic blood pressure of about 3–5 mmHg. Oral TU was not associated with liver toxicity nor did it cause an elevation in high-sensitivity C-reactive protein or lipoprotein-associated phospholipase A2 (cardiovascular safety biomarkers) after 365 days of therapy. Conclusion: A new oral TU formulation was safe and effective and represents a significant therapeutic advance for the treatment of appropriate hypogonadal men.

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Section: Resultsmentioning

confidence: 99%

Section: Patient Characteristics and Dispositionmentioning

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A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men

Swerdloff

Dudley

2020

Therapeutic Advances in Urology

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“…Little is published about the long-term efficacy of oral TU [ 69 ] and titration regimens for pubertal progression and completion [ 70 ]. To overcome the erratic absorption of oral TU, a new oral formulation that is less affected by the lipid content of meals was approved by the FDA for hypogonadism in men [ 93 ]. This formulation has not been studied in adolescents.…”

Section: Current Options For Testosterone Therapy In Adolescents Amentioning

confidence: 99%

Testosterone Use in Adolescent Males: Current Practice and Unmet Needs

Vogiatzi

Tursi

Jaffe

et al. 2020

Journal of the Endocrine Society

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Testosterone replacement therapy (TRT) is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. With many new testosterone (T) formulations entering the market targeted for adults, we review current evidence and TRT options for adolescents and identify areas of unmet needs. We searched PubMed for articles (in English) on testosterone therapy, androgens, adolescence, and puberty in humans. The results indicate that short-term use of T enanthate (TE) or oral T undecanoate is safe and effective in inducing puberty and increasing growth in males with CDGP. Reassuring evidence is emerging on the use of transdermal T to induce and maintain puberty. Long-term safety and efficacy of TRT for puberty completion and maintenance have not been established. Current TRT regimens are based on consensus and expert opinion, while evidence-based guidelines are lacking. Limited guidance exists on when and how T should be administered and optimal strategies for monitoring therapy once it is initiated. Only TE and T pellets are FDA approved for use in adolescent males in the US. Despite the introduction of a wide variety of new T formulations, they are designed for adults, and their metered doses are difficult to titrate in adolescents. In conclusion, TRT in adolescent males is hindered by lack of long-term safety and efficacy data and limited options approved for use in this population. Additional research is needed to identify the route, dose, duration, and optimal timing for TRT in adolescents requiring androgen therapy.

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“…CV events were not different between arms. It should be noted that two separate studies using oral testosterone undecanoate and sub‐cutaneous testosterone enanthate showed small but significant increase in systolic BP with testosterone treatment 49,50 …”

Section: Adverse Eventsmentioning

confidence: 99%

Reflections on the T Trials

Swerdloff

Wang

2020

Andrology

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Background This manuscript is a review and discussion of the published results of the T Trials. Objective To re‐examine the efficacy of testosterone replacement of hypogonadal men >65 years of age in the T Trials. Materials and Methods The T Trials were a complex collection of seven double blind, placebo‐controlled trials of the efficacy of testosterone as replacement therapy for older men with unequivocal hypogonadism. There were three main trials (sexual function; physical function; vitality) and four sub‐trials (cognition; bone; anemia; and cardiovascular). All subjects participated in the main trials while more selective inclusion/exclusion criteria existed for the sub‐trials. Subjects were excluded for perceived higher risk of prostate cancer and recent myocardial or cerebral vascular events. Results The previously published results are reviewed here as seen in the context of this special issue on late‐onset hypogonadism. In the T Trials, positive benefits were seen in the sexual function, bone, and anemia trials with small but significant benefits in the vitality trial. No benefit was seen in the cognition trial, partial benefit in physical function, and a negative benefit outcome seen in the cardiovascular trial. The later trial was underpowered and the results were described as exploratory. Adverse events were relatively uncommon in the 12‐month treatment phase and additional 12‐month post‐treatment phase. The most frequent adverse effect ascribed to testosterone was erythrocytosis. Conclusions The T Trials studied the efficacy of testosterone replacement therapy on 788 men with low testosterone and symptoms of hypogonadism. The studies demonstrated benefits in four trials (sexual function, vitality, bone, and anemia); partial benefit in the physical function trial; no effect in the cognition trial; and a negative effect in the exploratory cardiovascular trial. The T Trials were not designed to assess long‐term risks of testosterone in men.

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A New Oral Testosterone Undecanoate Formulation Restores Testosterone to Normal Concentrations in Hypogonadal Men

Cited by 66 publications

References 29 publications

A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men

A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men

Testosterone Use in Adolescent Males: Current Practice and Unmet Needs

Reflections on the T Trials

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