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036 Assessment of Fasting and Varying Meal Fat Content on the Bioavailability of Oral Testosterone Undecanoate (LPCN 1021) in Hypogonadal Men
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Proceedings of the 21st Annual Fall Scientific Meeting of SMSNA, Las Vegas, Nevada, USA, November 19-22, 2015
increased from 203 to 530 (p<0.0001). Mean RHI improved from 1.74 to 2.07 (p¼0.03). Mean AI improved from 4.2% to -0.89% (p¼0.01). In 4 men RHI worsened but in each case the decrease was less than the 10% error of the test (1.3-6.3%). No man had worsening of AI. Conclusions: Men with symptomatic hypogonadism often have abnormal arterial endothelial function. Following TRT, this endothelial function either remains unchanged or improves. This improvement would be expected to reduce the risk of subsequent cardiac events. Disclosure: Work supported by industry: no. The presenter or any of the authors act as a consultant, employee (part time or full time) or shareholder of an industry. 036 ASSESSMENT OF FASTING AND VARYING MEAL FAT CONTENT ON THE BIOAVAILABILITY OF ORAL TESTOSTERONE UNDECANOATE (LPCN 1021) IN HYPOGONADAL MEN Khera, M.1,*; Dobs, A.S.2; Miner, M.M.3; Wang, C.4; Delconte, A.5; Chidambaram, N.6; Nachaegari, S.6; Patel, M.6 1 Baylor College of Medicine, Houston, TX, USA; 2Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Brown University and the Miriam Hospital, Providence, RI, USA; 4 Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, USA; 5St Joseph’s University, Philadelphia, PA, & Lipocine, Inc., Salt Lake City, UT, USA; 6 Lipocine, Inc., Salt Lake City, UT, USA Objective: To evaluate effects of fasting and varying food fat content on the pharmacokinetics of serum testosterone following administration of a single dose of 225 mg LPCN 1021 in hypogonadal men. Methods: A single-center, open-label, randomized, single-dose, 4-way crossover study of LPCN 1021 in 13 hypogonadal (mean (SD) baseline testosterone 275(42) ng/dL) men was conducted. Men received 225 mg LPCN 1021 under fasted conditions as well as under the following 3 fed conditions: 800 to 1000 calorie meal with 15% of calories from fat, low fat meal (LFM i.e. 15g of
Figure 1.
fat), 30% calories from a standard fat meal (SFM, i.e. 30 gm of fat), and 50% calories from a high fat meal (HFM i.e. 50 gm of fat) with washout of 4 days between each period. Results: The mean (% CV) of AUC0-t and Cmax after taking 225mg of LPCN in the fasting state were 7423 (19) ng.h/dL and 562 (26) ng/dL, respectively. The mean serum testosterone levels for men in the LFM, SFM, and HFM groups increased significantly with a mean (% CV) AUC0-t of 10429 (19) ng.h/dl, 10421 (16) ng.h/dl, and 11974 (18) ng.h/dL, respectively and a mean (% CV) Cmax of 1570(35) ng/dL, 1560(30) ng/dl, and 1680(44) ng/dl, respectively without significant difference between the three meals (p>0.05) with fat significantly different (p <0.001) when compared with the fasting state. Conclusion: Under fasting condition, administration of LPCN 1021 resulted in low serum testosterone concentrations. Any fatty meal resulted in 60% more bioavailable serum testosterone levels compared to fasting state. Serum testosterone concentrations are not affected by the amount of fat (from 15gm to 50gm) content taken with LPCN 1021. Men ingesting a LFM with LPCN 1021 had similar serum testosterone levels as those men ingesting a SFM or HFM. Therefore, LPCN 1021 performance is consistent, predictable and oral absorption did not vary significantly with the fat content between 10 and 50 % of fat of the meal. Disclosure: Work supported by industry: yes, by Lipocine, inc. (industry initiated, executed and funded study). The presenter or any of the authors act as a consultant, employee (part time or full time) or shareholder of an industry.
037 TWICE WEEKLY DOSING OF INJECTABLE TESTOSTERONE ASSOCIATED WITH INCREASED ERYTHROCYTOSIS Ohlander, S.J.1,*; Varghese, B.1; Jones, M.1; Lindgren, M.C.1; Herati, A.S.1; Pastuszak, A.W.1; Lipshultz, L.I.1 1 Baylor College of Medicine, USA Objectives: The most common dose-limiting adverse effect of testosterone (T) therapy (TTh) is erythrocytosis, which may increase the risk for thromboembolic complications. We sought to determine if the incidence of erythrocytosis, as defined by a hematocrit (Hct) > 52%, could be avoided by more frequent, lower dose T injections. Materials and Methods: A sample of 55 men using injectable T (cypionate or enanthate) at a single dose and frequency was selected for analysis from The Baylor Men’s Health Database. Age, T dose and frequency of administration, Hct and during of TTh were extracted. Groups were divided into 27 men on 200 mg T once weekly (QW) and 28 men on 80-160 mg of T twice a week (BIW). BIW dosing was initiated in men in whom hypogonadal symptoms returned prior to administration of their next dose. Maximum Hct was determined for each patient and the cohort mean of these maxima calculated. Mann-Whitney U analysis was used to compare differences between numerical variables. J Sex Med 2016;13:S1eS71
Proceedings of the 21st Annual Fall Scientific Meeting of SMSNA, Las Vegas, Nevada, USA, November 19-22, 2015
increased from 203 to 530 (p<0.0001). Mean RHI improved from 1.74 to 2.07 (p¼0.03). Mean AI improved from 4.2% to -0.89% (p¼0.01). In 4 men RHI worsened but in each case the decrease was less than the 10% error of the test (1.3-6.3%). No man had worsening of AI. Conclusions: Men with symptomatic hypogonadism often have abnormal arterial endothelial function. Following TRT, this endothelial function either remains unchanged or improves. This improvement would be expected to reduce the risk of subsequent cardiac events. Disclosure: Work supported by industry: no. The presenter or any of the authors act as a consultant, employee (part time or full time) or shareholder of an industry. 036 ASSESSMENT OF FASTING AND VARYING MEAL FAT CONTENT ON THE BIOAVAILABILITY OF ORAL TESTOSTERONE UNDECANOATE (LPCN 1021) IN HYPOGONADAL MEN Khera, M.1,*; Dobs, A.S.2; Miner, M.M.3; Wang, C.4; Delconte, A.5; Chidambaram, N.6; Nachaegari, S.6; Patel, M.6 1 Baylor College of Medicine, Houston, TX, USA; 2Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Brown University and the Miriam Hospital, Providence, RI, USA; 4 Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, USA; 5St Joseph’s University, Philadelphia, PA, & Lipocine, Inc., Salt Lake City, UT, USA; 6 Lipocine, Inc., Salt Lake City, UT, USA Objective: To evaluate effects of fasting and varying food fat content on the pharmacokinetics of serum testosterone following administration of a single dose of 225 mg LPCN 1021 in hypogonadal men. Methods: A single-center, open-label, randomized, single-dose, 4-way crossover study of LPCN 1021 in 13 hypogonadal (mean (SD) baseline testosterone 275(42) ng/dL) men was conducted. Men received 225 mg LPCN 1021 under fasted conditions as well as under the following 3 fed conditions: 800 to 1000 calorie meal with 15% of calories from fat, low fat meal (LFM i.e. 15g of
Figure 1.
fat), 30% calories from a standard fat meal (SFM, i.e. 30 gm of fat), and 50% calories from a high fat meal (HFM i.e. 50 gm of fat) with washout of 4 days between each period. Results: The mean (% CV) of AUC0-t and Cmax after taking 225mg of LPCN in the fasting state were 7423 (19) ng.h/dL and 562 (26) ng/dL, respectively. The mean serum testosterone levels for men in the LFM, SFM, and HFM groups increased significantly with a mean (% CV) AUC0-t of 10429 (19) ng.h/dl, 10421 (16) ng.h/dl, and 11974 (18) ng.h/dL, respectively and a mean (% CV) Cmax of 1570(35) ng/dL, 1560(30) ng/dl, and 1680(44) ng/dl, respectively without significant difference between the three meals (p>0.05) with fat significantly different (p <0.001) when compared with the fasting state. Conclusion: Under fasting condition, administration of LPCN 1021 resulted in low serum testosterone concentrations. Any fatty meal resulted in 60% more bioavailable serum testosterone levels compared to fasting state. Serum testosterone concentrations are not affected by the amount of fat (from 15gm to 50gm) content taken with LPCN 1021. Men ingesting a LFM with LPCN 1021 had similar serum testosterone levels as those men ingesting a SFM or HFM. Therefore, LPCN 1021 performance is consistent, predictable and oral absorption did not vary significantly with the fat content between 10 and 50 % of fat of the meal. Disclosure: Work supported by industry: yes, by Lipocine, inc. (industry initiated, executed and funded study). The presenter or any of the authors act as a consultant, employee (part time or full time) or shareholder of an industry.
037 TWICE WEEKLY DOSING OF INJECTABLE TESTOSTERONE ASSOCIATED WITH INCREASED ERYTHROCYTOSIS Ohlander, S.J.1,*; Varghese, B.1; Jones, M.1; Lindgren, M.C.1; Herati, A.S.1; Pastuszak, A.W.1; Lipshultz, L.I.1 1 Baylor College of Medicine, USA Objectives: The most common dose-limiting adverse effect of testosterone (T) therapy (TTh) is erythrocytosis, which may increase the risk for thromboembolic complications. We sought to determine if the incidence of erythrocytosis, as defined by a hematocrit (Hct) > 52%, could be avoided by more frequent, lower dose T injections. Materials and Methods: A sample of 55 men using injectable T (cypionate or enanthate) at a single dose and frequency was selected for analysis from The Baylor Men’s Health Database. Age, T dose and frequency of administration, Hct and during of TTh were extracted. Groups were divided into 27 men on 200 mg T once weekly (QW) and 28 men on 80-160 mg of T twice a week (BIW). BIW dosing was initiated in men in whom hypogonadal symptoms returned prior to administration of their next dose. Maximum Hct was determined for each patient and the cohort mean of these maxima calculated. Mann-Whitney U analysis was used to compare differences between numerical variables. J Sex Med 2016;13:S1eS71