The product development efforts at CONRAD have broadened substantially over the past few years. These expanded efforts have focused on the development of new tenofovir (TFV) and combination microbicide formulations as well as manufacturing clinical trial supplies.
TFV Vaginal Gel
CONRAD supplies the microbicide field with TFV 1% gel for a range of clinical trials. This gel has been or is being evaluated in several studies sponsored by the Microbicide Trials Network (MTN) to assess safety, pharmacokinetics (PK)/pharmacodynamics (PD), adherence and efficacy. The product development group is responsible for the manufacturing, packaging, labeling, and distribution of the clinical supplies in accordance with current Good Manufacturing Practices (cGMPs). CONRAD’s product development team worked with contract manufacturing organizations to provide clinical supplies, including placebo gel, for the CAPRISA 004, VOICE and FACTS 001 clinical trials.
TFV Rectal Gel
CONRAD collaborated with the Microbicide Trials Network to develop a TFV gel for rectal use. In early studies of the TFV vaginal gel used rectally, some participants experienced gastrointestinal distress, so CONRAD scientists reformulated the gel by reducing the osmolality in hopes of reducing this side effect. Results from the MTN-007 study showed that the reduced-glycerin gel is safe and well-tolerated and an expanded safety study - MTN-017 - is ongoing in men who have sex with men and in transgender women.
TFV Intravaginal Ring
CONRAD is committed to the development of a sustained release intravaginal ring (IVR) for TFV. This product is designed to release TFV over the course of 90 days. The IVR is based on the use of a novel biocompatible polyurethane thermoplastic designed specifically to control the release of TFV.
TFV and TFV/FTC Vaginal Tablets
Vaginal tablets are small and easy to store, can be used without a partner’s knowledge and are inexpensive. CONRAD is developing vaginal tablets containing either TFV alone or TFV combined with emtricitabine (FTC), the same combination in the antiretroviral pill Truvada. Preclinical testing of TFV prototype tablets in rabbits has shown similar drug levels in vaginal tissues and fluids and lower levels in plasma compared to TFV gel. Testing of the TFV/FTC tablets in rabbits showed the same results for TFV levels; FTC levels were high 4 hours after administration, but dropped off more than TFV at 24 hours. No safety issues have been identified in animal testing of the tablets.
Development of Sustained-Release Injectable Contraceptive Steroid Product
CONRAD is developing a sustained release injectable contraceptive product based on levonorgestrel butanoate (LNG-B) in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development. This compound is a hydrophobic prodrug of LNG. The prodrug is micronized to the desired size range under aseptic conditions, then prepared as an aqueous suspension drug product. Once injected, the LNG-B slowly dissolves and is subsequently hydrolyzed to form the active progestin, LNG. Through proper control of particle size, the release of LNG from the LNG-B is expected to last for 4 to 6 months in vivo.
Multipurpose Technologies (MPTs)
A significant number of women, especially in developing countries, need protection against more than one STI, particularly HIV and herpes simplex virus-2 (HSV-2), and family planning methods to prevent unplanned pregnancies. MPTs are designed to address multiple indications with one product. CONRAD has been at the forefront of both STI prevention and contraception. To that end, we are actively pursuing development of novel MPTs designed to prevent both pregnancy and HIV/HSV-2:
SILCS Diaphragm Combined with Reformulated TFV Gel
CONRAD scientists are reformulating TFV gel with enhanced contraceptive properties. This new gel will be used with the SILCS diaphragm to prevent pregnancy, HIV and HSV-2. After successful formulation, the new gel will be tested for safety and efficacy in animals. If results from the animal trials are favorable, the combination will then be tested simultaneously in humans in a postcoital test (to determine if sperm are present in a woman’s mid-cycle mucus after sex while using the SILCS plus TFV) and in a safety and PK/PD trial.
This IVR combines TFV and levonorgestrel (LNG) to provide a ring capable of preventing HIV transmission and pregnancy for 90 days. Animal testing performed to date shows favorable TFV and LNG concentrations in the blood and tissues and no safety concerns. The first clinical trial of the ring will assess PK/PD and safety and began in 2014.