Introduction: Current testosterone replacement therapies have limited acceptability: gels can be messy and risk inadvertent dosing of others; injections are painful; and oral testosterone undecanoate (TU) delivers variable testosterone levels, requires concurrent ingestion of a fatty meal and may produce supraphysiological dihydrotestosterone (DHT) levels1. We present the first human trial of an oral native testosterone preparation formulated to deliver testosterone irrespective of food intake.
Aim: To compare the pharmacokinetics of DITEST (Diurnal Ltd Cardiff, UK) to an oil based oral TUformulation (Andriol Testocaps, MSD, UK) and explore the effect of food on DITEST bioavailability.
Methods: Single centre, phase 1b study of DITEST in 25 adult males with hypogonadism, one subject withdrawn after single period and only included in safety analysis (Clinicaltrials.gov: NCT02966652). Part 1 compared the pharmacokinetics of 80 mg TU with 120 mg DITEST after a high fat meal. Part 2 the pharmacokinetics of 200mg of DITEST administered fed and fasted. Results are baseline adjusted.
Results: DITEST showed a testosterone dose response between 120 mg and 200 mg with Cmax 19.1 and 30.4 nmol/l and AUC (0–10 h) 59.5 and 88.6 h*nmol/l. DITEST 200 mg gave an equivalent Cmax and AUC(0–10 h) to TU 80 mg: Cmax 30.4 vs 31.4 nmol/l and AUC (0–10 h) 88.6 vs 102 h × nmol/l. Serum TU levels after dosing with 80 mg testosterone undecanoate were 10-fold greater than the testosterone levels generated by TU. Fed and fasted DITEST had similar pharmacokinetics Cmax26.5 vs 30.4 nmol/l, AUC (0–10) (87.0 vs 88.6). Both dose strengths of DITEST resulted in lower levels of DHT than TU 80 mg; Cmax 2.9 [120 mg DITEST] vs 4.5 [200 mg DITEST] vs 6.7 [80 mg TU] nmol/l and AUC (0–10) (11.0 [120 mg DITEST] vs 16.7 [200 mg DITEST] vs 36.3 [80 mg TU] h × nmol/l). There was one serious adverse event (urinary retention) during TU dosing. There was no emerging safety concern.
Discussion: Administration of DITEST in fed and fasted states provides similar testosterone and DHT exposure. TU levels were much higher than testosterone levels suggesting a large proportion of testosterone undecanoate was not converted to testosterone. Compared to published literature on a self-emulsifying formulation of TU at 200 mg, DITEST at 200mg provides a similar testosterone Cmax and no requirement for a fatty meal1.
Conclusion: DITEST is an oral native testosterone formulation with anticipated advantages over current oral therapy of dosing without food and less risk of high DHT levels compared to TU therapy.
1. Yin AY et al., J Androl 2012 33 190–201.
05 Sep 2020 - 09 Sep 2020