Testosterone Nasal Gel Research Articles

PMON268 A Multicenter, Open Label, Variable Dose, Two-Arm, Pilot Paediatric Phase 1 Pk Study To Evaluate 4.5% Testosterone Nasal Gel In Hypogonadal Boys

Abstract Introduction Testosterone treatment is regularly required by adolescent boys with hypogonadism. Aim To evaluate the pharmacokinetics of a nasal testosterone gel, which is available for adult men with hypogonadism, in adolescents. Methods Open-label, variable-dose, non-randomized, 3-treatment crossover study of testosterone nasal gel 4.5% w/w (Natesto™). Subjects were hypogonadal adolescent boys between the ages of 12.0–17.9 years. Biochemical analyses were performed by Acerus Pharma. Summary and Conclusions Testosterone nasal gel 4.5% w/w (Natesto™) represents a safe and acceptable method of administering testosterone to hypogonadal adolescents. Based on feedback from both patients and investigators, the nasal gel was well tolerated by patients, and it was felt that children would be able to administer this independently. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Study shows patients have a positive perception of testosterone nasal gel.

Study shows patients have a positive perception of testosterone nasal gel.

Efficacy of Nasal Testosterone Gel (Natesto®) Stratified by Baseline Endogenous Testosterone Levels.

ObjectivePharmacokinetic and efficacy data from a phase 3 testosterone nasal gel (TNG) study were stratified by baseline endogenous testosterone level in patients with testosterone deficiency. Total testosterone (TT), LH, and FSH levels, as well as erectile function, mood, and lean body mass for each group were compared. In a subset of patients with very low baseline endogenous testosterone levels (<100 ng/dL), we investigated whether TNG is a suitable treatment option.Materials and MethodsPatients with testosterone deficiency (serum TT <300 ng/dL) were treated with TNG for 3 months, followed by safety extension periods of 90 and/or 180 days. Pharmacokinetic parameters were calculated from serum hormone levels on days 30 and 90, along with efficacy measurements, which were analyzed by comparison with baseline values. Baseline and/or predose TT values were used for patient stratification.ResultsPrestudy and predose endogenous testosterone concentrations correlated. The maximal concentration of TT was nearly identical across all cohorts at days 30 and 90, whereas the average concentration over 24 hours had a slight positive dependence relative to predose levels. LH levels remained in the normal range but were decreased more in patients with higher starting baseline levels. These findings indicate that TNG works with an active hypothalamic-pituitary-gonadal axis that responds to each dose of TNG throughout the treatment period. Patients with the lowest endogenous testosterone levels received maximum exposure impact from each TNG dose. Patients with severe testosterone deficiency had similar efficacy improvements as the remainder of the study population.ConclusionAll testosterone-deficient cohorts were successfully treated with TNG.

SUN-220 The Effect of Testosterone Nasal Gel on Reproductive Hormones and Semen Parameters

PURPOSE: To evaluate the effects of testosterone nasal gel on reproductive hormones and semen parameters after 3 and 6 months of therapy. HYPOTHESIS: Exogenous testosterone use leads to negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis and inhibits male fertility. Because testosterone nasal gel is short-acting and more closely mimics normal physiology, we hypothesized that it will have less inhibitory effect on the HPG axis and allow for maintained spermatogenesis. MATERIALS AND METHODS: We prospectively enrolled men aged 18-55 with at least two T levels < 350 ng/dL (drawn before 10 AM) and two semen analyses (SA) with total motile sperm count (TMSC) > 5 million. Eligible men were treated with testosterone nasal gel three times daily for a period of 6 months. T, LH, FSH, semen analysis (X 2), International Index of Erectile Function (IIEF), and Short Form Health Survey (SF-36) were collected at baseline and after 3 and 6 months of therapy. A single testosterone level was collected after 1 month. Hormone levels were drawn with 2 hours after administering nasal testosterone. Data are presented as median (interquartile range); medians were compared using the Mann-Whitney test, significance was set at p<0.05. RESULTS: We have enrolled 36 men. Mean age is 36.8 years. A total of 25 men have completed 1 month of therapy, 12 have completed 3 months, and 7 have completed 6 months. T increased significantly from baseline 238.5 (197.5-282.0) ng/dl to 554 (359.5-778.0) ng/dl at 1 month, 509.8 (318.3-919.1) ng/dl at 3 months and 629.0 (447.4-784.2) ng/dl at 6 months (p<0.05 at 1,3 and 6 months). LH declined from a baseline of 4.3 (2.2-4.5) IU/ml to 2.0 (1.1-3.6) IU/ml at 3 months and 1.9 (0.6-3.1) IU/ml at 6 months (p<0.5 at 3 and 6 months). FSH declined from a baseline of 3.2 (2.3-5.8) IU/ml to 2.7 (1.1-3.6) IU/ml at 3 months and 2.1 (1.3-7.4) IU/ml at 6 months. This decline was not statistically significant at 6 months (p=0.16). Median FSH levels remained within normal lab range (1.5-12.4 IU/ml). Median TMSC remained statistically unchanged, 29.0 (14.5-41.0) million at baseline, 31.5 (13.8-62) million at 3 months and 26.0 (3.75-51.8) million at 6 months. No men became azoospermic while on nasal testosterone. IIEF and SF-36 remained statistically unchanged. CONCLUSION: This is an interim analysis of a phase IV clinical trial. Nasal gel testosterone increased serum T levels while maintaining FSH levels within normal range and, importantly, maintained semen parameters. Nasal gel testosterone has the potential to be paradigm-shifting in our approach to develop a safe and effective treatment for men with low T who wish to restore normal serum T levels while preserving fertility.

The My-T study: Patient satisfaction and preference comparing topical and nasal testosterone therapies.

Natesto®, testosterone nasal gel (TNG) is an intranasal testosterone therapy (TTh) used to restore testosterone levels and improve symptoms of hypogonadism. Treatment requires application two (bid) or three (tid) times daily. The Treatment Satisfaction Questionnaire for Medication (TSQM) and a Patient Preference and Use (PPU) Questionnaire were used to obtain patient feedback on the use of TNG and compare to experience with topical TTh. The study enrolled 24 TTh-naive (TThN) and 93 TTh-experienced (TThE) hypogonadal men. Treatment lasted up to 120 days, with titration at day 90 to determine the most appropriate dose for restoration of testosterone levels (11 mg bid or tid). Patient satisfaction and symptom changes were measured at days 0, 30, 60, 90, and 120. The PPU Questionnaire was performed at study entry and study completion. Symptoms improved from baseline (30.6) to day 90 (35.1) (p<0.0001; +15%), consistent with testosterone replacement. TNG increased scores for effectiveness (+20%), convenience (+30%), and global satisfaction (+3%) as compared to their previous topical TTh. TThE patients reported ease of use, convenience, efficacy/effectiveness, and travel friendliness as "likes" of TNG therapy. Overall, 67.2% of patients agreed or strongly agreed that they preferred TNG over topical TTh and 59% sought a prescription to continue treatment with TNG. Patients switching from topical TTh to TNG reported significant improvements in symptoms and patient satisfaction compared to their previous topical TTh. Patients also reported a significant improvement in convenience with TNG despite two to three times daily application. Preference, satisfaction, and convenience may translate to better treatment compliance.

MY-T study: Symptom-based titration decisions when using testosterone nasal gel, Natesto®.

Natesto®, testosterone nasal gel (TNG), is a testosterone therapy (TTh) indicated for adult male hypogonadism. This study allowed titration decisions to be based on physicians' assessment of patient symptoms. Hypogonadal males on active topical testosterone therapy (TThE) or naive to any form of testosterone therapy (TThN) were treated with 22 mg TNG daily (11 mg twice daily) for 90 days. Titration was determined by the physician at day 90 wherein the dose was increased to 33 mg daily if symptoms were not properly managed. Total testosterone (TT) levels were collected at day 90 and 120 and the quantitative Androgen Deficiency in the Aging Male (qADAM) symptom questionnaire was administered on days 0, 30, 60, 90, and 120. At study endpoint, 77.0% of all patients were in the normal TT range. Mean qADAM scores increased from 30.8 at baseline to 35.5 (6.6) at day 90. Physician assessments resulted in 37% patients being up-titrated for an additional 30 days, however, qADAM scores did not change significantly at the higher dose. The majority of patients achieved the normal range of testosterone with TNG when physicians based their titration decision on an assessment of symptoms. Sexual function and energy-related symptoms were predictive of improvements resulting from treatment. These symptoms were the most relevant indicators for physicians in making decisions relating to titration.

Phase 1 pharmacokinetics and phase 3 efficacy of testosterone nasal gel in subjects with seasonal allergies.

NATESTO® testosterone nasal gel (TNG) is a liquid gel that is applied in the nose for the treatment of male hypogonadism. There is a reasonable concern that administration of TNG to patients with active rhinitis could modify absorption. Results from two clinical studies are reported wherein subjects with allergic rhinitis (AR) subjects are treated with TNG. The 24-hour pharmacokinetics (PK) and relative bioavailability of serum total testosterone (sTT) from TNG (11 mg tid ) were determined using a phase 1 Latin-square design with 18 eugonadal AR subjects crossed over between asymptomatic, symptomatic-untreated, and symptomatic-treated (oxymetazoline) conditions. Allergy symptoms, assessed using Total Nasal Symptom Score (TNSS), were induced using grass pollen in an allergy challenge chamber (ACC) prior to administration of TNG. The data are discussed in relation to results from a phase 3 study in 306 hypogonadal patients which compare clinical outcomes of AR and non-AR patients treated with TNG. PK analysis (Tmax, maximum observed concentration [Cmax], area under the curve [AUC]) of sTT showed no difference in the rate or extent of absorption of exogenous testosterone from TNG as a function of allergy symptoms. The relative bioavailability also showed all three conditions to be equivalent. However, pre-dose mean sTT in AR patients was 21-25% lower when symptomatic vs. asymptomatic, which is attributed to the allergic reaction. A large phase 3 study, based predominantly on PK measures of sTT, showed that clinical outcomes for AR and non-AR patients treated with TNG were identical, including the percentage of patients in the eugonadal range, hormone profiles, and adverse events. AR does not affect absorption of TNG. Patient outcomes for long-term treatment with TNG for up to one year are not dependent on AR history.

Meeting summaries: Major depressive disorder, obesity, diabetes, cancer

■ Results of a Phase III trial with Natesto by Trimel, the testosterone nasal gel, in 306 men with low testosterone from 39 outpatient centers in the United States showed that threetimes daily dosing was more effective than twice-daily dosing at raising testosterone blood levels within the normal range; 90% of men who used the nasal gel three times daily compared with 71% of men using it twice daily achieved appropriate levels.

Oritavancin diphosphate.

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The December 2014 monograph topics are olodaterol, peginterferon beta-1a, testosterone nasal gel, ferric citrate corredination complex, and safinamide. The Safety MUE is on olodaterol.

Oritavancin diphosphate.

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The December 2014 monograph topics are olodaterol, peginterferon beta-1a, testosterone nasal gel, ferric citrate corredination complex, and safinamide. The Safety MUE is on olodaterol.