LIVINGSTON, N.J., May 4 /PRNewswire-FirstCall/ -- Results of an international multicenter study comparing the steady-state pharmacokinetics and tolerability of Striant(R) (testosterone buccal system) (CIII) with a testosterone containing skin patch show that use of Striant produces physiologic (normal) testosterone levels in hypogonadal men and achieves testosterone concentrations within the normal range.
Hypogonadism, a condition associated with a deficiency or absence of endogenous testosterone, affects nearly five million American men. Study results are published in this month's issue of the Journal of Clinical Endocrinology and Metabolism.
In the open-label, parallel arm study, 66 patients with a morning serum testosterone less than 6.94 nmol/liter were randomized into two groups. Of the 57 patients who completed the study protocol, 29 patients were treated with Striant (30 mg) twice daily for seven days, while 28 patients in the other group applied a transdermal testosterone patch daily for seven days. Serum testosterone and dihydrotestosterone (DHT) concentrations were measured periodically over six days and then serially over the last 24 hours of the study. The average serum testosterone concentration over 24 hours showed a mean of 18.74 nmol/liter in the Striant group, and 12.15 nmol/liter in the transdermal patch group (P<0.01). Serum testosterone concentrations of 10.41 to 36.44 nmol/liter are accepted as within the normal range.
Of the patients treated with Striant, 97 percent had average steady-state testosterone concentrations within the physiologic range, while only 56 percent of the transdermal patch patients achieved physiologic testosterone concentrations (P<0.001 between groups). Also, testosterone concentrations were within the physiologic range in the Striant group for a significantly greater portion of the last 24-hour dosing interval on day seven than in the transdermal patch group (mean, 84.9 percent vs. 54.9 percent; P <0.001). Few patients experienced adverse effects from either treatment, and no significant local tolerability problems were noted with Striant.
"Some transdermal testosterone therapies are limited by inconsistent absorption of the hormone," said investigator Marta Korbonits, M.D., Ph.D., clinician scientist in the department of endocrinology at St. Bartholomew's Hospital in London. "However, this study demonstrates that Striant is a valuable addition to the range of choices for testosterone replacement therapy because of its ability to provide steady-state testosterone levels in the blood well within the physiologic range, and with a high level of local tolerability."
Additional Striant Data Published
Results of a separate, randomized, open-label comparative study published recently in Current Medical Research & Opinion demonstrate that buccal administration of testosterone with Striant results in physiologic (normal) total testosterone levels. These data confirm the results of previous Striant studies in a total of 125 hypogonadal men. The study also demonstrated that Striant does not result in adverse, potentially harmful levels of other systemic androgens, specifically DHT.
A total of 28 subjects were randomized to Striant (30 mg) twice daily or a transdermal testosterone gel system (5 g packets) once daily for two weeks. At the conclusion of the study period, total testosterone values were comparable in the Striant group (16.7 nmol/liter) and the transdermal gel group (15.3 nmol/liter). Differences in DHT concentrations between the Striant and transdermal gel groups were statistically significant, with mean DHT levels on Day 14 of 1.9 nmol/liter for Striant and 3.2 nmol/liter for the transdermal gel (P=0.006). There was a statistically significant difference (P<0.001) in the mean T/DHT ratio on Day 14-15 between the Striant group (9.3) and the transdermal gel group (5.0). Normal T/DHT ratio ranges are between 9 and 12. All adverse events in this study were considered mild to moderate in severity.
"Striant provides a safe, effective and convenient treatment option for testosterone replacement therapy in hypogonadal men," said study author Adrian S. Dobs, M.D., MHS, professor of medicine and oncology in the Division of Endocrinology and Metabolism at Johns Hopkins Medical Center. "Striant delivers the appropriate range of the hormone without the need for titration."
"Androgen deficiency is the most common hormone deficiency disorder among men as they age," said George W. Creasy, M.D., vice president of clinical research at Columbia Laboratories. "Because of its unique delivery system, Striant is the only buccal system available that allows for controlled and sustained release of testosterone. As a result, Striant delivers consistent blood levels of the hormone without titration. These study results add to the growing body of knowledge regarding the efficacy and safety of Striant and provide physicians and their patients with a unique delivery system in the treatment of hypogonadism."
About Hypogonadism
Hypogonadism (low testosterone) can be caused by conditions associated with the testes, pituitary gland or hypothalamus gland, or by a genetic disorder. Signs and symptoms of hypogonadism can include decreased libido (sexual desire), erectile dysfunction (ED), fatigue, depression, reduced muscle mass, and osteoporosis. Testosterone replacement therapy helps to provide and maintain normal levels of testosterone.
About Striant
Prior to the introduction of Striant, patients with hypogonadism have been treated with transdermal patches, topical gels, injectable formulations of testosterone or surgically-inserted testosterone implants. Striant utilizes Columbia's proprietary Bioadhesive Delivery System (BDS), including its patented progressive hydration buccal technology to deliver testosterone via the buccal cavity twice daily. Striant provides the first commercial opportunity for this buccal delivery platform, which may be used to investigate whether it can deliver other previously approved and marketed drugs that cannot be ingested. The controlled- and sustained-release buccal testosterone product (which has the appearance of a small monoconvex tablet) acts by adhering to the buccal mucosa, the small, natural depression in the mouth where the gum meets the upper lip above the incisor teeth. As it is exposed to saliva the product softens into a gel-like form, which remains comfortably in place over each 12-hour dosing period. The product delivers testosterone through the buccal mucosa, where it is absorbed into the bloodstream and delivered directly into the superior vena cava (major blood vessel), bypassing the gastrointestinal system and liver. Striant is able to produce circulating testosterone concentrations in hypogonadal males that approximate physiologic levels seen in healthy young men. Striant is available in a single strength, and no dose titration is required.
The clinical data supporting the FDA approval of Striant were generated from a 12-week U.S. multicenter, open-label, single arm trial that evaluated the efficacy, safety and tolerability of Striant in 98 hypogonadal men. Of the 82 patients who completed the trial, 86.6 percent had an average testosterone concentration within the physiologic (normal) range at the end of 12 weeks. Striant was also evaluated in a seven-day, multicenter, open-label European parallel trial with 29 patients receiving Striant. At the conclusion of this trial, 97 percent of Striant patients had an average testosterone concentration within the physiologic (normal) range. The novel buccal delivery was well-accepted by patients in these clinical studies.
On June 19, 2003, the U.S. Food and Drug Administration (FDA) approved Striant(R) (testosterone buccal system) mucoadhesive (CIII), the first-ever transbuccal (gum surface) treatment for testosterone replacement therapy in men for conditions associated with a deficiency or absence of endogenous testosterone, including hypogonadism.
Important Safety Information
In the U.S. pivotal trial involving 98 patients, the most frequent adverse events that occurred with an incidence of one percent or greater which were possibly, probably, or definitely related to the use of Striant were: gum or mouth irritation (9.2%), bitter taste (4.1%), gum pain (3.1%), gum tenderness (3.1%), headache (3.1%), gum edema (2.0%), and taste perversion (2.0%). A total of 16 patients reported 19 gum-related adverse events. Of these, 10 patients (10.2%) reported 12 events of mild intensity, 4 patients (4.1%) reported 5 events of moderate intensity, and 2 patients (2.0%) reported 2 events of severe intensity. Four patients (4.1%) discontinued treatment with Striant due to gum or mouth-related adverse events including 2 with severe gum irritation, 1 with mouth irritation, and 1 with "bad taste in mouth." The majority of the gum-related adverse events were transient and resolved within 1 to 14 days. Patients should be advised to regularly inspect the gum region where they apply Striant and report any abnormality to their health care professional.
Striant is not indicated for women and must not be used in women. Testosterone supplements may cause fetal harm. Striant should not be used in patients with known hypersensitivity to any of its ingredients including testosterone USP that is chemically synthesized from soy.
Androgens are contraindicated in men with carcinoma of the breast or known carcinoma of the prostate. Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required. Gynecomastia frequently develops and occasionally persists in patients being treated with androgens for hypogonadism. The treatment of hypogonadal men with testosterone esters may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases. Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and therefore, insulin requirements.
On March 4, 2004, Striant was approved for marketing in the United Kingdom by the Medicines and Healthcare Products Regulatory Agency (MHRA). Columbia announced last year a license and supply agreement for Striant in eighteen European countries with Ardana Bioscience, Ltd.
About Columbia Laboratories
Columbia Laboratories, Inc. is a U.S.-based international pharmaceutical company dedicated to the development and commercialization of women's health care and endocrinology products, including those intended to treat infertility, dysmenorrhea, endometriosis, hormonal deficiencies and reducing the risk of pre-term labor. Columbia is also developing a buccal delivery system for peptides. Columbia's products primarily utilize the company's patented Bioadhesive Delivery System (BDS) technology. For more information, please visit http://www.columbialabs.com/.
This press release contains statements that constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Those statements include statements regarding the intent, belief or current expectations of the company and its management team. Investors are cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and that actual results may differ materially from those projected in the forward-looking statements. Such risks and uncertainties include, among other things, the successful marketing of Striant(R), the impact of competitive products and pricing; success in obtaining acceptance and approval of new products by FDA and international regulatory agencies; competitive economic and regulatory factors in the pharmaceutical and healthcare industry, and general economic conditions, and other risks and uncertainties that may be detailed, from time- to-time, in Columbia's reports filed with the Securities and Exchange Commission. The company undertakes no obligation to publicly update any forward-looking statements.
Please refer to full prescribing information for additional information.
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