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March 9, 2015
Antares Pharma issued results of an ongoing,
multi-center, phase III clinical study
of enanthate administered once-weekly by
subcutaneous injection using the QuickShot
auto injector in testosterone deficient adult
males. In the study, 150 adult males with
hypogonadism (low testosterone) and testosterone
blood levels less than 300ng/dL
received a starting dose of 75mg of subcutaneously
administered testosterone enanthate
(QuickShot Testosterone, or QS T) once
weekly for six weeks. Blinded adjustments
to dose were made when necessary at week
seven based upon the week six pre-dose
blood level, and full pharmacokinetic (PK)
profiles were obtained during the 12th week
of treatment. The primary endpoint of the
population that received one or more doses
of QS T was met by 139 out of 150 patients,
equating to 92.7% with a 95% confidence
interval of 87.3% to 96.3%. Among the 137
patients that completed all 12 weeks of dosing
and PK sampling, 98.5% were within the
pre-defined range. The top-line results are
summarized in the table below. Overall, the
regimen demonstrated a mean (± standard
deviation) steady state concentration of
testosterone of 553.3 ± 127.3ng/dL at 12
weeks. The company will be filing an NDA
with the FDA and, at the recommendation
of the FDA, the company anticipates that
it may need approximately 70 additional
April 8, 2013
Repros Therapeutics released results from a phase II trial of Androxal (ZA-301) for secondary hypogonadism. This randomized, placebo-controlled study enrolled 151 males with secondary hypogonadism. Subjects received doses of Androxal between 12.5mg and 25mg, or placebo. After six weeks of dosing, subjects were allowed to up-titrate if their morning testosterone was below 300ng/dL. Results showed 79% of the intent-to-treat Androxal subjects exhibited 24-hour average testosterone levels in the normal range (300-1040ng/dL). In a separate “completer” analysis, 83% of men who completed the study and the 24-hour assessment were in the normal range and exhibited a mean 24-hour average testosterone of 425ng/dL (standard deviation, 135). By comparison, the mean 24-hour average for the placebo group was 234ng/dL (standard deviation, 74.1). The difference between the drug and placebo result was highly statistically significant. Androxal was well tolerated. There were no adverse events leading to discontinuation in the Androxal arm. Based on these data, Repros Therapeutics hopes to fully enroll the sister pivotal study with ZA-302 by the end of May.
August 15, 2011
Repros Therapeutics released interim results from a phase II trial of Androxal for hypogonadal men with type II diabetes. Data are from 61 subjects who completed a three month dosing regimen of Androxal 12.5 or 25 mg or placebo. At baseline, mean morning testosterone levels for the three groups were 224.9 ng/dl, 238.2 ng/dl and 233.8 ng/dl for the placebo and Androxal 12.5 and 25 mg arms, respectively. At the end of the three month dosing period the mean morning testosterone levels increased to 234.2 ng/dl, 463.5 ng/dl and 444.7 ng/dl, respectively. Both Androxal arms were highly statistically different from placebo (p<0.0001). In the group of subjects that achieved a morning level of testosterone >450 ng/dl and met the per protocol requirement of BMI <40 (n≡14) a statistically significant reduction in HbA1c was observed compared to placebo (p≡0.02). There was a concurrent reduction in fasting plasma glucose levels in the responding Androxal arms (men > 450ng/dl) of -21 mg/dl compared to the placebo group which exhibited a slight increase of 2.0 mg/dl.
October 12, 2009
Repros reported positive results from a phase II trial of Androxal for secondary hypogonadism. This three-arm, randomized, open-label, fixed dose, active-control study enrolled male subjects, 46 to 51 years of age, who were previously treated with a topical testosterone gel. The men were randomized to one of two treatment arms. A third arm was added after the first two arms were fully recruited. Group A (n≡7) underwent a three week washout period followed by 25 mg Androxal daily for 6 months. Group B (n≡5) underwent a three week washout period followed by Testim 1% gel for 6 months. Group C (n≡9) underwent a three month washout period followed by 25 mg Androxal daily for 6 months. Group A vs. Group B: At 6 months of treatment, there was a statistically significant increase in mean TT compared with baseline in both treatment groups. At 6 months, mean TT levels were 545 ± 269 and 525 ± 256 ng/dL for the men receiving Testim and Androxal, respectively, compared to baseline levels of 165 ± 66 ng/dL. Androxal consistently elevated sperm counts into the normal range after 3 and 6 months of treatment and at follow-up (mean values > 147 x 106/ml). The sperm count was statistically significantly higher in the Androxal than the Testim treated group at 3 (p≡0.004) and 6 months (p≡0.009). Androxal also stimulated statistically significant increases in LH and FSH compared to Testim at all time points. The baseline LH and FSH levels were 1.02 ± 1.44 mIU/ml and 0.99 ± 1.00 mIU/ml, respectively. Androxal increased mean LH significantly at 3 months to 5.7 ± 3.2 mIU/ml (p≡0.013) and to 6.1 ± 3.1 mIU/ml (p≡0.004) at 6 months. The mean FSH levels for men on Androxal were 4.5 ± 2.4 mIU/ml at 3 months (p≡0.015) and 5.5 ± 2.5 mIU/ml at 6 months (p≡0.003). Group C: Although a normalization of sperm count was observed during the three month off-treatment study run-in period, testosterone levels remained below normal (mean TT 214.00 ± 44.50 ng/dl). However, Repros was not able to collect meaningful data on the men in this group due to lost follow-up and/or poor adherence at month 3 and 6, prohibiting comparisons with Groups A and B.
October 5, 2009
Acrux released positive results from a phase III trial of Axiron for the treatment of hypogonadism. This international, open-label trial enrolled 155 men who applied one of four doses of Axiron to an area under the armpit once daily for four months. The primary objective was to demonstrate that Axiron restores average blood levels of testosterone into the normal range. After four months of treatment with Axiron, 84% of subjects achieved average blood levels of testosterone within the normal range, exceeding the pre-determined requirement of 75%. After two weeks of treatment, it was found that 76% of subjects had average blood levels of testosterone within the normal range. The average baseline testosterone level in subjects prior to treatment was 190ng/dl. At four months, the average testosterone level was 504ng/dl (the normal range being 300-1,050ng/dl). In addition, analysis of mood, sexual desire, sexual activity and sexual performance before and after four months of treatment showed significant improvement from baseline across all measures. Treatment was safe and well tolerated, with no reports of treatment-related adverse reactions.
June 30, 2008
Prostrakan issued positive results from a phase III trial of Tostran for the treatment of hypogonadism. This randomized, double-blind, placebo-controlled, multi-center, international study, dubbed TIMES 2 (Testosterone replacement In hypogonadal men with either MEtabolic Syndrome or type 2 diabetes), enrolled 220 male subjects. The subjects received Tostran (2% testosterone gel) or placebo gel, applied once a day to the thigh or abdomen, and were followed for a year. The primary endpoint of the study was to determine the effect of Tostran on insulin resistance in all subjects, as measured by homeostasis model assessment as an index of insulin resistance (HOMA-IR). The primary endpoint was met, with a statistically significant improvement in insulin sensitivity in the Tostran arm at six and 12 months (p=0.05 and p=0.01, respectively). In addition, the subjects using the testosterone gel saw significant improvement in sexual function at six and 12 months (p <0.05). Based on the results Prostrakan plans to file for US regulatory approval later in 2008.
January 28, 2008
Diamyd Medical issued positive long-term results from a phase IIb trial of Diamyd for the treatment of type I diabetes. This randomized study enrolled seventy pediatric and adolescent subjects in Sweden. The subjects received two single injections of Diamyd or placebo. The primary endpoint was preservation of beta cell function as measured by C-peptide. Thirty months after the first injection, preservation of insulin was significantly higher in subjects receiving Diamyd, both in the fasting state and after meal stimulation, compared with placebo-treated subjects. Diamyd also increased GAD antibody levels at fifteen and twenty one months post-injection. Based on the data, phase III trials are planned.
Indevus reported results from a phase III trial of Nebido for the treatment of hypogonadism. This open label trial enrolled one hundred and thirty male subjects with hypogonadism. The subjects received an initial injection of 750 mg of Nebido, followed four weeks later by an additional 750 mg loading injection and then 750 mg injections every ten weeks thereafter. The primary endpoint was responder analysis, defined as a one who, during steady state, had an average concentration of serum total testosterone (Cavg) within the normal range (300 to 1000 ng/dL). The primary response endpoint was met if at least 75% of patients achieved a Cavg within this normal range. In addition, maximum testosterone (Cmax) levels were evaluated. This endpoint was reached if no subjects exceeded a testosterone concentration of 2500 ng/dL, no more than 5% exceeded a concentration of 1800 ng/dL, and no more than 15% of exceeded a concentration of 1500 ng/dL. Of the one hundred and seventeen subjects who completed the study, 94% had Cavg levels within the normal range. None of these subjects exceeded a testosterone level of either 2500 ng/dL or 1800 ng/dL, and nine (7.7%) had a peak level exceeding 1500 ng/dL. Steady state testosterone pharmacokinetics were achieved within weeks under the new regimen, whereas the 1000 mg regimen reached steady state pharmacokinetics after several months. An NDA is currently under review by the FDA for a 1,000 mg dose of Nebido. Based on the results, Indevus intends to ask for approval of this 750 mg regimen rather than the higher treatment schedule.
June 18, 2007
Bionovo reported positive results from a phase II trial of MF101 for the treatment of hot flashes associated with menopause. This double-blind, placebo- controlled, randomized trial enrolled 217 women in the US. Subjects received MF101 (5 grams/day), MF101 (10 grams/day), or placebo for twelve weeks. The primary endpoints were to assess the safety, tolerability and the potential efficacy of two doses of MF101 to reduce the frequency and severity of hot flashes. In terms of the number of hot flashes per day, MF101 (5 gm) was more effective than placebo at 12 weeks but did not reach statistical significance (p=0.06). MF101 (10 gm) did reach significance compared to placebo (p=0.05). Both doses combined were superior to placebo (p=0.04). In terms of reducing the severity of hot flashes, MF101 showed a trend towards improvement over placebo for both the 5 gm dose (p=0.12) and the 10 gm dose (p=0.1) and was superior to placebo with both doses combined (p=0.08). The percent of women reporting greater than 50% reduction in all hot flashes was statistically significantly higher in the MF101 high dose group compared to placebo (p=0.03) and in both doses of MF101 combined compared to placebo (p=0.05). Based on the results, Bionovo plans to advance MF101 into future trials.
Indevus announced positive results from a phase III trial of Nebido for the treatment of male hypogonadism. This randomized, open-label study enrolled 237 subjects who received Nebido dosed as either 1000 mg every 12 weeks or as 750 mg every 12 weeks, both via intramuscular injection. The endpoint was responder analysis, defined as a subject who, during a steady state, had an average concentration of serum total testosterone (Cavg) within the normal range (300 to 1000 ng/dL). This endpoint was met if 75% of the subjects achieved Cavg levels within this range. Of the subjects in the 1000 mg arm receiving their fourth injection, 94% a Cavg level within the normal range over the course of the 12 week injection period. In addition, no subjects in the 1000 mg arm exceeded a testosterone concentration of 2500 ng/dL. Of the subjects in the 750 mg arm receiving their fourth injection, 86% had a Cavg within the normal range. No subjects in the 750 mg arm exceeded a testosterone level of either 2500 ng/dL or 1800 ng/dL. Based on the results, Indevus plans to submit a NDA to the FDA later in 2007.
June 11, 2007
Repros announced positive results from a phase III trial of Androxal for the treatment of male secondary hypogonadism. This six month, double-blind trial enrolled 199 subjects, 144 of whom completed the study. Subjects received one of two doses of oral Androxal (12.5mg and 25mg), matching placebo capsules or open label Androgel, at any dose to be used per manufacturer's instructions. The primary endpoints were the proportion of subjects at month three who showed morning total serum testosterone concentrations within the normal physiological range (300 to 1040 ng/dl) and non-inferiority to Androgel. At month three, the proportion of subjects in the Androxal 12.5mg and 25mg treatment arms with normal serum testosterone concentrations was 72.7% and 79.2%, respectively. This was seen in 57.4% of those receiving Androgel and 28.3% of those on placebo. Both doses of Androxal were superior to placebo (p less than 0.0001). In addition, these results confirmed non-inferiority to Androgel. Based on the results, Repros plans to meet with the FDA to determine the optimal path towards NDA submission.
August 8, 2005
Auxilium reported top line results of a phase II trial of their androgen replacement transmucosal film, for the treatment of male hypogonadism. Preliminary data yielded evidence of efficacy, with 3 doses of the film each yielding increases in serum testosterone levels; the efficiency of absorption indicated that the lowest trial dose would be optimal for future studies. The film had a positive overall tolerability profile, and 97% of subjects indicated that the film treatment was "desirable" or "acceptable." This open-label study enrolled 69 hypogonalal men, who received daily applications of the film at one of three dose levels (5 mg, 10 mg or 15 mg).
November 22, 2004
Auxilium Pharmaceuticals reported positive results of a clinical trial of their approved testosterone replacement gel Testim in hypogonadal HIV-positive men. Top-line results indicate that the drug was efficacious in treating symptoms of hypogonadism, with significant improvements observed in reported sex drive, erectile function, and sexual-satisfaction with sex life, as well as satisfaction with androgen therapy. These improvements in sexual function resulted in a significantly fewer Testim treated men requiring titration to a higher dose compared to men treated with AndroGel, another approved topical testosterone therapy (30% vs. 74%; p<0.05). This approved-therapy controlled study enrolled a total of 48 HIV-positive hypogonadal men who had not achieved adequate symptom relief on AndroGel.
June 24, 2002
Phase III trial results suggest that long-term use of Unimed Pharmaceuticals' AndroGel (testosterone gel), a transdermal hormone replacement therapy, is safe and effective in men with low testosterone. The trial included 92 hypogonadal men with an average age of 52 years. Subjects received continuous replacement with testosterone gel for up to 42 months (average of 29 months). At six months, results showed that sexual motivation and performance improved significantly in subjects receiving testosterone gel, and this effect was maintained throughout treatment. An average decrease of 2.5 kg in fat mass was observed at 30 months, in addition to an average increase in lean body mass of 3.5 kg. Bone mineral density was increased at six months, and it remained increased by approximately 4% in the spine and 2% in the hip at 30 months.