Efficacy and Safety of a New Oral Testosterone (TU) Formulation in Hypogonadal Men: Results from the ‘inTUne’ Trial
Ronald Swerdloff, MD1, Christina Wang, MD1, Stanton Honig, MD2, John K. Amory, MD3, James Longstreth, PhD4, Marc Gittelman, MD5, Jed Kaminetsky, MD6, Brooke Harnisch, MD7, Robert Dudley, PhD8.
1Lundquist Institute at Harbor-UCLA, Torrence, CA, 2Yale University School of Medicine, New Haven, CT, 3University of Washington, Seattle, WA, 4Longstreth & Associates, Mundelein, IL, 5South Florida Medical Research, Aventura, FL, 6Manhattan Medical Research, New York, NY, 7UConn Health, Farmington, CT, 8Clarus Therapeutics, Northbrook, IL.
Introduction: Oral delivery of testosterone (T) replacement therapy (TRT) has several potential advantages over currently available options. A novel formulation of oral TU was studied in two prior Phase 3 trials that demonstrated safety and efficacy. However, to further improve pharmacokinetic (PK) efficacy, a new dose titration algorithm was evaluated. Methods: Hypogonadal men (diagnosis consistent with the Endocrine Society guideline of two morning serum T < 300 ng/dL and signs/symptoms with hypogonadism), age 18 - 65 y/o, were recruited into a 105 day, randomized, open-label, multicenter, dose-titration trial. Patients were randomized 3:1 to oral TU, BID (JATENZO®; n=166) or a topical T product QD (Axiron®; n=56). Dose titration was based on average T levels (Cavg) calculated from serial 24h pharmacokinetic (PK) samples. T was assayed by LC-MS/MS. Patients had two dose adjustment opportunities (on study day 21 and 56), which were based on plasma T levels (Cavg) calculated from multiple PK samples, prior to final PK visit. Safety was assessed by standard clinical measures, including ambulatory BP. Results: 87% of patients in both groups achieved mean T Cavg in the eugonadal range. NaF-EDTA plasma T Cavg for oral TU group was 403 ± 128 ng/dL (~14 ± 4 nmol/L; mean ± SD) [serum T equivalent ~ 489 ± 155 ng/dL (17 ± 5 nmol/L)] and for topical T (Axiron®) was 391 ± 140 ng/dL (~14 ± 5 nmol/L). The overall safety profile of TU was similar to topical T. There were no deaths or T-related serious adverse events. Mean changes in HCT and PSA were similar in both treatment arms with HCT increase of 2-3% (absolute increase) and PSA increase of 0.2-0.3 ng/mL with no PSA values > 4 ng/mL. Final subject mean increase in systolic BP by cuff in the oral TU and topical T groups was 2.8 (± 11.84) and 1.8 (± 10.76), respectively. Conclusion: A new oral TU formulation restored T to mid-eugonadal levels in hypogonadal patients. Both groups showed a modest change in HCT and PSA.
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