Tommy Wall
Member
Since somethime Testavan is a new option at least in some parts in Europe. It seems to be a good option to other gels. Anyone that could share some info reg this gel?
New Testo gel (Testavan)
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madman
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Testosterone gel 2%, developed by Ferring Pharmaceuticals, is a novel hydroalcoholic, homogeneous, transparent, nonstaining, and highly viscous topical gel formulation with a hands-free cap applicator that allows precise dispensing and application on the shoulder or upper arm. The cap applicator helps minimize the risk of secondary testosterone exposure in children and women and has shown better compliance than hand application (Dobs et al., 2012; Efros, Carrara, & Neijber, 2015). Previous studies have shown that testosterone gel 2% is rapidly absorbed in a dose-dependent manner leading to normalization of testosterone levels (Dean, Carnegie, Rodzvilla, & Smith, 2004). The present phase 3 study (000023, NCT01665599) and its 6-month extension study (000077, NCT01703741) evaluated the efficacy, safety, local tolerability, and pharmacokinetics (PK) of testosterone gel 2% in hypogonadal men.
2.4 | Study treatments
Subjects applied testosterone gel 2% on clean dry skin between 6:00 a.m. and 10:00 a.m., alternatively to each upper arm/shoulder area using a cap applicator. Each pump actuation delivered 1.15 ml gel corresponding to 23 mg testosterone. The application site was allowed to dry for about 5 min before being covered, and the subjects were instructed to wash their hands and avoid contact with the application site with children, pregnant women, and partners. Subjects were also instructed not to bathe at least 6 hr after the gel application, and to avoid direct sunlight on the application area.
In study 000023, the starting dose for all subjects was 46 mg of testosterone gel 2%. The dose could be up-titrated or down-titrated to 69 mg or 23 mg, respectively, at two time points (Day 21 and Day 56), based on a morning pre-dose serum testosterone sample (titration range 300–600 ng/dl) taken on Day 14 and Day 49. In study 000077, subjects continued with the dose established on Day 56, except for those having maximum testosterone concentration (Cmax) total testosterone level ≥1500 ng/dl on Day 90/91 of study 000023 that could not be explained as a spurious result (a high pre-dose testosterone level or levels inconsistent with a dihydrotestosterone [DHT] level). In this case, the dose was down-titrated by 1 pump actuation right at the start of study 000077.
3 | RESULTS
Of 180 subjects receiving study drugs (safety and ITT populations), 172 subjects completed study 000023 (FAS population). Of these, 154 were included in the PP population. Of 172 subjects completing study 000023, 145 were enrolled in study 000077 (safety and ITT populations), and 127 subjects completed the study. Overall 110 subjects completed the 9-month of treatment period (FAS population) and had 24-hour testosterone PK data. The baseline characteristics of subjects are presented in Table 1. In study 000023, five subjects were down-titrated to 23 mg, 155 subjects were up-titrated to 69 mg and 12 subjects remained on the 46 mg dose. The initial dose for the 106 subjects (PP population) rolling over to study 000077 was fixed, based on the Day 56 titrations. However, 52 subjects with Cmax total testosterone level ≥1500 ng/dl on Day 90/91 of study 000023 were down-titrated by 1 pump actuation. These subjects remained on the same dose till the end of study 000077 with no further dose titrations (10 were on 23 mg; 40 were on 46 mg and 56 were on 69 mg dose).
4 | DISCUSSION
The present study demonstrated that treatment with testosterone gel 2% was efficacious in normalizing the serum testosterone levels and had an acceptable tolerability profile. The responder rate was greater than 82% for both studies and was considered comparable to other testosterone gels although with a much lesser dose. This can be attributed to its novel hydroalcoholic transdermal gel formulation with high bioavailability facilitating quick absorption through the skin with a cap applicator providing the ease of hands-free administration. The formulation and the hands-free application may also minimize the risk of secondary exposure to testosterone
Testosterone levels reached the maximum values between 2 and 4 hr at Month 3 and Month 9, indicating a rapid absorption at the site of application, with testosterone peak levels similar to normal physiological levels. The 24-hour average testosterone levels at Month 3 were well above the lower limit of the normal values, that FIGURE 4 SF-12: QoL survey. MCS, Mental Component Summary; PCS, Physical Component Summary; QoL, Quality of Life; SF, Short Form Cmax (ng/dl) Study 000023, N (%) Extension study 000077, N (%) ≥1500 and ≤1799 20 (11.6) 6 (5.7) ≥1800 and ≤2499 18 (10.5) 3 (2.8) ≥2500 14 (8.1) 3 (2.8) Total >1500 52 (30.2) 12 (11.3) Cmax, Serum testosterone maximum concentration observed. TABLE 2 Subjects with total testosterone Cmax (000023 and extension study 000077) 6 of 7 BELKOFF et al. is 515 ± 132 ng/dl, 407 ± 160 ng/dl, and 495 ± 184 ng/dl for 23 mg, 46 mg and 69 mg dose respectively. In TRiUS study, the average total testosterone levels were 485 ± 284 ng/dl at Month 3 (Miner, Bhattacharya, Blick, Kushner, & Khera, 2013), which increased to 500.6 ± 248.2 ng/dl following 12 months treatment (Khera et al., 2011); however, the doses used in this study were twice as high as used in present study. This suggests that lower doses of testosterone gel 2% used in the present study were efficacious in restoring serum testosterone levels, coupled with a significant improvement in sexual functioning, fatigue, and QoL.
In conclusion, testosterone gel 2% application was found to be efficacious with an acceptable safety profile in hypogonadal men. This study also gave an important insight into titration decision time points. The incidence of the testosterone Cmax >1500 ng/dl was greater than expected and for these subjects, the Cmax could have been reduced, while maintaining Cave within normal range. An improved titration schema, both with respect to dosing and titration decision time point, which could reduce the incidence of supraphysiological levels of serum testosterone levels, is also to be considered.
2.4 | Study treatments
Subjects applied testosterone gel 2% on clean dry skin between 6:00 a.m. and 10:00 a.m., alternatively to each upper arm/shoulder area using a cap applicator. Each pump actuation delivered 1.15 ml gel corresponding to 23 mg testosterone. The application site was allowed to dry for about 5 min before being covered, and the subjects were instructed to wash their hands and avoid contact with the application site with children, pregnant women, and partners. Subjects were also instructed not to bathe at least 6 hr after the gel application, and to avoid direct sunlight on the application area.
In study 000023, the starting dose for all subjects was 46 mg of testosterone gel 2%. The dose could be up-titrated or down-titrated to 69 mg or 23 mg, respectively, at two time points (Day 21 and Day 56), based on a morning pre-dose serum testosterone sample (titration range 300–600 ng/dl) taken on Day 14 and Day 49. In study 000077, subjects continued with the dose established on Day 56, except for those having maximum testosterone concentration (Cmax) total testosterone level ≥1500 ng/dl on Day 90/91 of study 000023 that could not be explained as a spurious result (a high pre-dose testosterone level or levels inconsistent with a dihydrotestosterone [DHT] level). In this case, the dose was down-titrated by 1 pump actuation right at the start of study 000077.
3 | RESULTS
Of 180 subjects receiving study drugs (safety and ITT populations), 172 subjects completed study 000023 (FAS population). Of these, 154 were included in the PP population. Of 172 subjects completing study 000023, 145 were enrolled in study 000077 (safety and ITT populations), and 127 subjects completed the study. Overall 110 subjects completed the 9-month of treatment period (FAS population) and had 24-hour testosterone PK data. The baseline characteristics of subjects are presented in Table 1. In study 000023, five subjects were down-titrated to 23 mg, 155 subjects were up-titrated to 69 mg and 12 subjects remained on the 46 mg dose. The initial dose for the 106 subjects (PP population) rolling over to study 000077 was fixed, based on the Day 56 titrations. However, 52 subjects with Cmax total testosterone level ≥1500 ng/dl on Day 90/91 of study 000023 were down-titrated by 1 pump actuation. These subjects remained on the same dose till the end of study 000077 with no further dose titrations (10 were on 23 mg; 40 were on 46 mg and 56 were on 69 mg dose).
4 | DISCUSSION
The present study demonstrated that treatment with testosterone gel 2% was efficacious in normalizing the serum testosterone levels and had an acceptable tolerability profile. The responder rate was greater than 82% for both studies and was considered comparable to other testosterone gels although with a much lesser dose. This can be attributed to its novel hydroalcoholic transdermal gel formulation with high bioavailability facilitating quick absorption through the skin with a cap applicator providing the ease of hands-free administration. The formulation and the hands-free application may also minimize the risk of secondary exposure to testosterone
Testosterone levels reached the maximum values between 2 and 4 hr at Month 3 and Month 9, indicating a rapid absorption at the site of application, with testosterone peak levels similar to normal physiological levels. The 24-hour average testosterone levels at Month 3 were well above the lower limit of the normal values, that FIGURE 4 SF-12: QoL survey. MCS, Mental Component Summary; PCS, Physical Component Summary; QoL, Quality of Life; SF, Short Form Cmax (ng/dl) Study 000023, N (%) Extension study 000077, N (%) ≥1500 and ≤1799 20 (11.6) 6 (5.7) ≥1800 and ≤2499 18 (10.5) 3 (2.8) ≥2500 14 (8.1) 3 (2.8) Total >1500 52 (30.2) 12 (11.3) Cmax, Serum testosterone maximum concentration observed. TABLE 2 Subjects with total testosterone Cmax (000023 and extension study 000077) 6 of 7 BELKOFF et al. is 515 ± 132 ng/dl, 407 ± 160 ng/dl, and 495 ± 184 ng/dl for 23 mg, 46 mg and 69 mg dose respectively. In TRiUS study, the average total testosterone levels were 485 ± 284 ng/dl at Month 3 (Miner, Bhattacharya, Blick, Kushner, & Khera, 2013), which increased to 500.6 ± 248.2 ng/dl following 12 months treatment (Khera et al., 2011); however, the doses used in this study were twice as high as used in present study. This suggests that lower doses of testosterone gel 2% used in the present study were efficacious in restoring serum testosterone levels, coupled with a significant improvement in sexual functioning, fatigue, and QoL.
In conclusion, testosterone gel 2% application was found to be efficacious with an acceptable safety profile in hypogonadal men. This study also gave an important insight into titration decision time points. The incidence of the testosterone Cmax >1500 ng/dl was greater than expected and for these subjects, the Cmax could have been reduced, while maintaining Cave within normal range. An improved titration schema, both with respect to dosing and titration decision time point, which could reduce the incidence of supraphysiological levels of serum testosterone levels, is also to be considered.
madman
Super Moderator
SUMMARY
Testosterone gel formulations have become a popular testosterone replacement therapy in patients with hypogonadism since their advent in the year 2000. The gel formulations restore testosterone levels to mid-normal physiological levels (14–17.5 nmol/L) as early as within 24 h and help alleviate the signs and symptoms of testosterone deficiency, thereby leading to an improved quality of life. Although testosterone gels have a favorable efficacy and safety profile as compared to injectable and patch formulations, the risk of secondary exposure poses a challenge. Approved testosterone topical formulations include Tostrex (Tostran, Fortesta), Androgel (Testogel), Testim, and Axiron (solution), which have a favorable efficacy profile and positively impact patient-reported outcome(s). Besides, Testavan, which is a 2% testosterone gel, is under registration in Europe and already approved in Australia in May 2017. Testavan uses a novel hydroalcoholic and highly viscous topical formulation. This product comes with a metered dose dispenser and a cap applicator that allows a hands-free application for precise dispensing and application. The present article provides a comprehensive review of the pharmacokinetic, tolerability, and safety profiles of the testosterone gels available in the market along with the new 2% testosterone gel, Testavan.
DEVELOPMENT OF TOPICAL TESTOSTERONE FORMULATIONS
Androgel 1% was the first topical gel formulation developed. The starting dose is 5 g (50 mg testosterone), which could be applied by hand over the shoulders/both arms/ abdomen. As a line extension, it was also approved in the EU as Androgel 1.62%, with a starting dose of 2.50 g (40.5 mg of testosterone), dispensed by two pump actuations and applied by hand over both shoulders and upper arms (Swerdloff et al., 2000; Kaufman et al., 2011, 2012). Testim (Testosterone 1%) was the second gel developed as a unit dose of 5 g tube of 1% strength containing 50 mg of testosterone, applied to the shoulders by hand (Steidle et al., 2003). Another product, Tostrex (Tostran), was developed as a 2% gel with a starting dose of 3 g (60 mg of testosterone, the dose could range from 20 to 80 mg, 20 mg increments), which could be applied to the abdomen or inside of both thighs by hand using a pump dispenser (SmPC Tostran). Similar to Tostrex, Fortesta 2% is applied to the inner thighs with a starting dose of 40 mg testosterone, adjusted in 10 mg testosterone increments for dose flexibility, with a minimum dose of 10 mg and a maximum dose of 70 mg testosterone (Dobs et al., 2012). Axiron is a 2% testosterone solution, approved in the United States and in some EU countries as well, with a starting dose of 60 mg. It is delivered via a metered pump that delivers 3 mL (30 mg) of testosterone to each underarm with a single actuation (Khera, 2016).
Testavan, the new 2% testosterone gel, uses a novel hydroalcoholic and highly viscous topical formulation. The product is homogeneous, transparent, and non-staining, and comes in a metered dose dispenser that includes a hands-free cap applicator for precise dispensing and application. The starting dose is 23 mg testosterone, delivered by one pump actuation, contained in 1.15 g of gel, and the highest dose is 3.45 g of gel containing 69 mg testosterone (delivered by three pump actuation) (Efros et al., 2016).
Compared to the other topical products, the amount of gel used with Testavan is generally less than the other products due to its higher bioavailability owing to its composition. In a randomized, active-controlled phase I study in down-regulated men, Testavan showed higher testosterone bioavailability, while delivering more testosterone in a small volume as compared with Androgel (Olsson et al., 2014). Also, there is no intended secondary exposure to the hands, which minimizes the risk of secondary exposure.
Serum testosterone concentration
Consistent with the guidelines, in two multicentre phase III studies, the mean Cave levels achieved with Testavan ranged from 12.8 to 17.5 nmol/L, similar to those achieved with Androgel 1.62%, Tostrex 2%, Fortesta 2% Testim 1% and Axiron solution (Table 1). Figure 2 shows the testosterone levels over time for Cave responders at Day 90 (Unpublished data).
Testavan gel provides the option of the lowest starting dose of 23 mg testosterone, which could go up to 46, and 69 mg as the maximum dose. The advantage of a lower starting dose with Testavan comes from Ferring Advanced Skin Technology (FAST), a proprietary topical gel technology developed by Ferring Pharmaceuticals. FAST relies on a unique combination of volatile/nonvolatile solvents and permeation enhancers that temporarily increase the skin permeability and hence reduce the volume of applied gel without high residual volume. However, as with most of the topical agents, risk of secondary exposure, especially for women and children, and the washout of testosterone while rinsing hands or showering is expected with Testavan also and has been thoroughly evaluated.
Testosterone gel formulations have become a popular testosterone replacement therapy in patients with hypogonadism since their advent in the year 2000. The gel formulations restore testosterone levels to mid-normal physiological levels (14–17.5 nmol/L) as early as within 24 h and help alleviate the signs and symptoms of testosterone deficiency, thereby leading to an improved quality of life. Although testosterone gels have a favorable efficacy and safety profile as compared to injectable and patch formulations, the risk of secondary exposure poses a challenge. Approved testosterone topical formulations include Tostrex (Tostran, Fortesta), Androgel (Testogel), Testim, and Axiron (solution), which have a favorable efficacy profile and positively impact patient-reported outcome(s). Besides, Testavan, which is a 2% testosterone gel, is under registration in Europe and already approved in Australia in May 2017. Testavan uses a novel hydroalcoholic and highly viscous topical formulation. This product comes with a metered dose dispenser and a cap applicator that allows a hands-free application for precise dispensing and application. The present article provides a comprehensive review of the pharmacokinetic, tolerability, and safety profiles of the testosterone gels available in the market along with the new 2% testosterone gel, Testavan.
DEVELOPMENT OF TOPICAL TESTOSTERONE FORMULATIONS
Androgel 1% was the first topical gel formulation developed. The starting dose is 5 g (50 mg testosterone), which could be applied by hand over the shoulders/both arms/ abdomen. As a line extension, it was also approved in the EU as Androgel 1.62%, with a starting dose of 2.50 g (40.5 mg of testosterone), dispensed by two pump actuations and applied by hand over both shoulders and upper arms (Swerdloff et al., 2000; Kaufman et al., 2011, 2012). Testim (Testosterone 1%) was the second gel developed as a unit dose of 5 g tube of 1% strength containing 50 mg of testosterone, applied to the shoulders by hand (Steidle et al., 2003). Another product, Tostrex (Tostran), was developed as a 2% gel with a starting dose of 3 g (60 mg of testosterone, the dose could range from 20 to 80 mg, 20 mg increments), which could be applied to the abdomen or inside of both thighs by hand using a pump dispenser (SmPC Tostran). Similar to Tostrex, Fortesta 2% is applied to the inner thighs with a starting dose of 40 mg testosterone, adjusted in 10 mg testosterone increments for dose flexibility, with a minimum dose of 10 mg and a maximum dose of 70 mg testosterone (Dobs et al., 2012). Axiron is a 2% testosterone solution, approved in the United States and in some EU countries as well, with a starting dose of 60 mg. It is delivered via a metered pump that delivers 3 mL (30 mg) of testosterone to each underarm with a single actuation (Khera, 2016).
Testavan, the new 2% testosterone gel, uses a novel hydroalcoholic and highly viscous topical formulation. The product is homogeneous, transparent, and non-staining, and comes in a metered dose dispenser that includes a hands-free cap applicator for precise dispensing and application. The starting dose is 23 mg testosterone, delivered by one pump actuation, contained in 1.15 g of gel, and the highest dose is 3.45 g of gel containing 69 mg testosterone (delivered by three pump actuation) (Efros et al., 2016).
Compared to the other topical products, the amount of gel used with Testavan is generally less than the other products due to its higher bioavailability owing to its composition. In a randomized, active-controlled phase I study in down-regulated men, Testavan showed higher testosterone bioavailability, while delivering more testosterone in a small volume as compared with Androgel (Olsson et al., 2014). Also, there is no intended secondary exposure to the hands, which minimizes the risk of secondary exposure.
Serum testosterone concentration
Consistent with the guidelines, in two multicentre phase III studies, the mean Cave levels achieved with Testavan ranged from 12.8 to 17.5 nmol/L, similar to those achieved with Androgel 1.62%, Tostrex 2%, Fortesta 2% Testim 1% and Axiron solution (Table 1). Figure 2 shows the testosterone levels over time for Cave responders at Day 90 (Unpublished data).
Testavan gel provides the option of the lowest starting dose of 23 mg testosterone, which could go up to 46, and 69 mg as the maximum dose. The advantage of a lower starting dose with Testavan comes from Ferring Advanced Skin Technology (FAST), a proprietary topical gel technology developed by Ferring Pharmaceuticals. FAST relies on a unique combination of volatile/nonvolatile solvents and permeation enhancers that temporarily increase the skin permeability and hence reduce the volume of applied gel without high residual volume. However, as with most of the topical agents, risk of secondary exposure, especially for women and children, and the washout of testosterone while rinsing hands or showering is expected with Testavan also and has been thoroughly evaluated.
Tommy Wall
Member
To me it seems interesting due to the absorvation capacity mas its far more expensive than injectable testo.
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