Zertane for Premature Ejaculation (PE)
Zertane is an oral drug candidate in successful late stage development as a proprietary treatment for premature ejaculation, a condition that has a major impact on the quality of life for men and their sexual partners. The active ingredient in Zertane™ has one or multiple mechanisms of actions that can delay ejaculation. This drug candidate also has a favorable safety record established during 30 years of human use. These unique pharmaceutical qualities, favorable human safety record, and a distinctive non-standard dosage not available in generic form, differentiate Zertane™ from other treatments for premature ejaculation. We intend that our labeling for Zertane™, if regulatory approval is obtained, will suggest “as required” dosing before sexual intercourse and not to exceed one tablet per day.
Initial randomized, controlled clinical trials (phase II) demonstrated that Zertane™ is an effective treatment with few adverse side effects for men with premature ejaculation. Men taking Zertane™ had significantly delayed intravaginal latency times (IELT), increased control of ejaculation, improved sexual satisfaction and less interpersonal distress compared to placebo. Zertane™ also demonstrated favorable safety profile in initial trials for premature ejaculation. No serious adverse side effects were caused by Zertane™.
Ampio completed the analysis of Phase III clinical trials conducted in Europe with Zertane™ as a fast dissolving oral tablet for premature ejaculation. Ampio believes Zertane™ represents a substantial global market opportunity and, to realize this opportunity and enhance Ampio’s global presence, has formed an international commercialization team to support the progression of Zertane™ through European and other international regulatory processes as well as outsourcing the manufacturing, supply and distribution of Zertane™.
No drug has yet been approved in the U.S. for the treatment of premature ejaculation, although an SSRI antidepressant drug and another prescription drug have been approved in some other countries. Both of these drug treatments are reported to have adverse effects that may limit their use.
Zertane Clinical Data
Six European clinical trials have been completed with Zertane: two Phase 1 trials in healthy volunteers and two Phase 2 and two Phase 3 trials in men with lifelong PE. The two Phase 1 safety trials were conducted to characterize the concentration of tramadol in plasma after oral administration of a single Zertane ODT (89 mg) in healthy volunteers.
Two randomized, placebo-controlled, blinded Phase 2 clinical trials were conducted in a total of 102 patients. The first of these showed that a single 25-mg dose of conventionally formulated immediate release tramadol hydrochloride (i.e., immediate-release gelatin capsules) was safe, well-tolerated and prolonged time to ejaculation in some, but not all, patients. The second trial evaluated three higher doses of tramadol hydrochloride: 65 mg, 85 mg and 120 mg. In this trial, a clear dose response was seen for both efficacy and safety, leading DMI Biosciences to conclude that the optimal tramadol dose to treat PE was likely to be in the range 60-90 mg.
Two placebo-controlled, randomized and double-blind Phase 3 clinical trials were conducted in Europe to investigate tramadol 62 mg and 89 mg ODT for the treatment of PE when taken as needed between two and eight hours before a sexual event. A total of 677 patients were randomized in the trials and received either the 62 or 89 mg ODT or a matching placebo ODT. Our claim that Zertane was efficacious in the Phase 3 trials is based on at least one of the two doses resulting in statistically significant improvements in both IELT and PEP measures (i.e. co-primary endpoints) from baseline to the end of the trial. Using IELT in combination with a self-report questionnaire (e.g. PEP or POPE) [has gained acceptance] as meaningful measures of pharmacoactivity and efficacy in the scientific and regulatory communities. The results of the Phase 3 trials suggest that tramadol 89 mg ODT is consistently more effective as a treatment for PE than tramadol 62 mg ODT. In accordance with the definitions from the clinical trial protocols, only the tramadol 89 mg ODT dose satisfied the claim for effective treatment of PE in both Phase 3 trials.
MiOXSYS™ for Male Infertility
Male Infertility and Oxidative Stress
Male infertility is a significant medical condition in which oxidative stress is well known to play a substantial role. The company is leveraging its MiOXSYS research tool to develop a clinical application – known as MiOXSYS – to assess oxidative stress levels in infertile males. Oxidative stress is well established as a leading contributing factor to male infertility. Further, a significant proportion of male infertility remains unexplained in part because of the lack of standardized tests available to clinicians and researchers to assess oxidative stress. This lack of standardization has resulted in poor implementation of semen and plasma analysis around the world.
MiOXSYS and Male Infertility
The company has conducted proof of concept studies in male infertility with a leading center in the United States and determined that oxidation-reduction potential effectively measures oxidative stress levels in semen and seminal fluid. Semen analysis studies are routinely conducted to assess causes of infertility, so we expect clinicians and oxidative stress researchers to readily integrate MiOXSYS into routine use. Additional studies are now underway that will determine the MiOXSYS system’s performance in semen analysis as it relates to infertility.