FDA Intrinsa Advisory Committee Background Document Overview
December 2, 2004
Proctor and Gamble submitted NDA 21-769 on June 21, 2004 for Intrinsa, testosterone transdermal system (TTS), for the following proposed indication:
"Treatment of hypoactive sexual desire disorder in surgically menopausal women receiving concomitant estrogen therapy. Hypoactive sexual desire disorder (HSDD) is the persistent or recurrent deficiency or absence of sexual thoughts, fantasies, and/or desire for or receptivity for sexual activity, which causes personal distress or interpersonal difficulties. Low sexual desire may be associated with low sexual activity, sexual arousal problems or orgasm difficulty."
The proposed dosing regimen is one TTS 300 mcg patch applied twice weekly on a continuous basis.
There is no product approved for this indication in the United States, and the Applicant undertook clinical development of this product following the FDA’s Draft Guidance on Female Sexual Dysfunction, which stresses the importance of using validated instruments for assessing responses to FSD therapy in specific target populations. The Applicant developed 3 psychometric instruments for use in the studies to assess the efficacy of TTS in treatment of HSDD in surgically menopausal women. The clinical program included two blinded, placebo-controlled Phase 3 studies (2001133 and 2001134) that each enrolled over 500 women. These studies were conducted in the US, Canada, Europe and Australia with more than 90% of the subjects from the US. The safety data base includes data from
Points to Consider
The major issues that the FDA would like the Advisory Committee for Reproductive Health Drugs to consider include:
3. Long Term Safety Assessment. FDA asks that the Advisory Committee for Reproductive Health Drugs consider whether there are unanswered safety questions that should be further assessed pre-approval in appropriately sized randomized trials of adequate duration, or whether these questions can appropriately be answered post-approval. Proctor and Gamble has proposed a post-marketing pharmacovigilance plan that focuses on a cohort study conducted in a claims-based database to address questions regarding the potential long term safety of TTS use. Should the Committee decide that the efficacy and safety data presented at this meeting support approval of the product, the FDA would like the Committee members to consider whether the Applicant’s pharmacovigilance plan is adequate to address unanswered questions about long term safety. Background rates of events of potential interest and time course of these events in women of this age group should be factored into these considerations, as well as the merit and feasibility of conducting trials of alternative designs (e.g., randomized controlled trials) in the population of interest.