Effects of a Novel Oral Testosterone Undecanoate on Ambulatory Blood Pressure in Hypogonadal Men

Abstract

Background: Testosterone replacement therapies may increase blood pressure (BP) with chronic use but the mechanism is not clear. TLANDO™ is a new oral testosterone undecanoate (TU) under development for the treatment of male hypogonadism. Methods: We studied the effects of the TU at 225 mg twice daily on ambulatory BP (ABP) and heart rate, in 138 men with hypogonadism (mean age, 54 years, 79% white, 48% with hypertension). Ambulatory BP and heart rate and hematologic assessments were obtained at baseline and following 4-months of therapy. Results: Changes from baseline in ambulatory 24-hour, awake, and sleep systolic BP (SBP) of 3.8 ( P < 0.001), 5.2 ( P < 0.001), and 4.3 mmHg ( P = 0.004) were observed post-treatment, respectively. Lesser changes in the diastolic BP (DBP) were observed (1.2 ( P = 0.009), 1.7 ( P = 0.004), and 1.7 mmHg ( P = 0.011) for 24-hour, awake, and sleep, respectively). Hematocrit and hemoglobin were increased by 3.2% and 0.9 g/dL ( P < 0.001), respectively. In those men in the top quartile of changes in hematocrit (range of 6% to 14%), the largest increases in ambulatory SBP (mean, 8.3 mmHg) were observed, whereas the changes in ambulatory SBP in the lower 3 quartiles were smaller (mean, 1.9, 3.3, and 2.1 mmHg in 1st, 2nd and 3 rd quartiles, respectively). Conclusion: These data demonstrate that small increases in ABP occurred following 4 months of the oral TU. For those men whose hematocrit rose by >6%, BP increases were of greater clinical relevance. Hence, hematocrit may aid in predicting the development of BP increases on testosterone therapy. ClinicalTrials.gov identifier: NCT 03868059.

A new oral testosterone (TLANDO) treatment regimen without dose titration requirement for male hypogonadism

“…Oral administration of TU has been shown to increase ambulatory blood pressures in previous literature 17,20,21 . The review report of Swerdloff et al.…”

“…There were no deaths and no treatment-related serious AEs. 21 The reports of these ambulatory BP monitoring studies with oral TU therapy conclude that although there are slight increases (about 3-5 mmHg) in ambulatory systolic BP with oral TU therapies, the clinical importance of the slight increase in systolic BP in hypogonadal men is unclear since men with T deficiencies have increased in cardiovascular risk. 22 In the current study, a clinical cuff BP measure was performed at baseline and each visit during the study.…”

“…Note that, 3.2% of the oral TU patients were started on new antihypertensive agents during the 180‐day study 20 . A recent ambulatory BP study of the current study drug (TLANDO) was performed for four months in 138 hypogonadal subjects 21 . Note that, 48% of the subjects had a medical history of hypertension or were receiving an anti‐hypertensive medication during therapy.…”

“…Oral administration of TU has been shown to increase ambulatory blood pressures in previous literature. 17 , 20 , 21 The review report of Swerdloff et al. on a recently approved oral TU product with dose titrations showed the oral TU increased mean ambulatory systolic/diastolic blood pressures (BPs) as 4.9 mmHg/2.8 mmHg for 3–4 months in 166 hypogonadal subjects.…”

“… 20 A recent ambulatory BP study of the current study drug (TLANDO) was performed for four months in 138 hypogonadal subjects. 21 Note that, 48% of the subjects had a medical history of hypertension or were receiving an anti‐hypertensive medication during therapy. The mean increases of systolic/diastolic BPs post‐4‐month therapy were 3.8 mmHg/1.2 mmHg.…”