28 Real-World Experience with First FDA-Approved Oral Testosterone Undecanoate Formulation
Authors: Dudley R , Newmark J , Stark S , Pheng L , Beliveau M , Longstreth J 
Published: April 2022

ABSTRACT

Introduction
The diagnosis of hypogonadism (HG) in men requires both consistently low testosterone (T) levels and signs and symptoms of T deficiency. Management of HG with T replacement therapy (TRT) aims to improve both low serum T levels and patients’ symptomatic complaints. The first oral softgel formulation of testosterone undecanoate (TU) was recently approved by FDA (JATENZO®) for TRT in men with specific hypogonadal conditions and is available in 3 capsule strengths and 5 dosage combinations for necessary dose adjustments. However, dose titration may not be necessary in many patients treated with this new oral TU formulation given the wide eugonadal range.

Objective
Assess the ability of any given daily dosage of oral TU to restore T to eugonadal levels without dose adjustment at steady state (Css); and determine real-world dose titration experience of patients treated with oral TU.

Methods
Pharmacokinetic (PK) simulations were performed using a robust population PK model developed for T in 474 hypogonadal men who were treated with oral TU in prior PK studies. The model consisted of a 1-compartment model with absorption lag time and an allometric function on key allometric parameters to account for differences in body weight. This final population PK model was coded in Trial Simulator v2.3.0.6 software. T levels were simulated following oral TU BID dosing on Day 55 (i.e., at steady state) with no dose adjustments. Average T concentrations (Cavg) were derived from multiple serial blood samples collected over 24 hrs for oral TU doses of 237, 316, and 396 mg TU, BID (without dose modification). The percent of subjects with T levels within the eugonadal range (serum Cavg between 304 ng/dL-1030 ng/dL) at each of these TU dose levels was calculated. Prescription data was also accessed in the Symphony PatientSource Patient Transactional Dataset to evaluate the frequency of real-world dose titration.

Results
The percentage of subjects with Css T Cavg within the eugonadal range for 237, 316, and 396 mg TU, BID were 61%, 74% and 74%, respectively. These corresponded to mean [5%, 95% CI] serum T levels (ng/dL) of 398 [389, 406], 560 [549, 572] and 728 [715, 741] ng/dL, respectively. Early assessment of real-world prescribing data for JATENZO indicated 35% of patients underwent dose titration by month 5.

Conclusions
Simulated daily BID dosing of oral TU without dose adjustment yielded eugonadal T levels in most subjects at all 3 dose levels examined. These data are consistent with initial early real-world experience with oral TU that indicates dose titration has not been required in most patients. However, because the desired outcome of TRT therapy focuses on both T Cavg and symptomatic response, this oral TU formulation enables necessary dose adjustment when needed.

Disclosure
Yes, this is sponsored by industry/sponsor: Clarus Therapeutics, Inc.

Clarification
Industry initiated, executed and funded study
Any of the authors act as a consultant, employee or shareholder of an industry for: Clarus Therapeutics, Inc.