Phase II year
2017
(last award dollars: 2020)
Phase II Amount
$3,951,347
The goal of this project is to develop a novel vaginal contraceptive gel product containing PPCM sodium salt (PPCM). PPCM is a novel polymer drug that inhibits infection of HSV, HIV, N. gonorrhea and is also contraceptive. This novel drug has an average molecular weight of 3900, is designed to be used topically, and thus far passed all safety studies and does not appear to be systemically absorbed. PPCM has been the subject of several publications. Development of a topical gel containing PPCM as a preventive and treatment product for genital herpes has been funded through three earlier STTR/SBIR grants. We have taken the drug from the bench to a defined drug with a full suite of analytical methods, a defined manufacturing method with a C of A and Reference Standard Batch, conducted two forced degradation studies, numerous formulations and numerous animal safety and efficacy studies. Under this grant proposal we will conduct all tasks required to generate the final Pharmacology/Toxicology, Chemistry Manufacturing and Controls (CMC) information required for IND submission of a vaginal contraceptive gel. 1) The current formula will be modified by Dr. Sanjay Garg to increase viscosity and mucoadhesion. We call this drug product Yaso-CON. The newly formulated Yaso-CON, appropriate for vaginal application will be transferred to our manufacturing partner who will scale up the product under cGMP, producing clinical trial samples, stability study samples and additional lots of drug product for final preclinical toxicology studies. 2) We will evaluate two lab assays developed by the inventors and one commercial assay for future use as a biomarker in Phase 1 clinical trials. We would like to have an assay that can guide us in determining final concentration of the active drug, rather than depending on pregnancy in women to give us that answer. If our research under this grant is fruitful, we will have an assay to determine contraceptive activity of post-coital vaginal secretions collected from women in Phase 1. This will guide our Phase 2 dose range finding study and final formulation. 3) A rabbit contraceptive study and GLP preclinical toxicology studies will be completed at appropriate CROs. 4) Phase 1 and 2 clinical trials will be developed. Feedback on these trials from FDA will be sought. An IND will be prepared and submitted. At the conclusion of this grant work we will have an active IND with clinical trial samples, ready to conduct Phase 1 human clinical trials.
Public Health Relevance Statement: NARRATIVE The purpose of this grant is to support development of polyphenylene carboxymethylene sodium salt (PPCM), a new active pharmaceutical ingredient (API), as a safe and effective coitally-dependent vaginal contraceptive. The need for birth control is undisputed. Around 40% of pregnancies worldwide are unintended 45% of pregnancies in the US continue to be unplanned higher than in other industrialized countries (1, 2). But obtaining birth control is complex. Effectiveness, accessibility and availability, cost, side effects, ease of use, and personal health factors influence the contraceptive practices of individual women (3-5). Yet contraceptive choices for women are too limited. The most effective modern contraceptives are long acting, reversible, hormone-based methods. But women also need access to methods which do not require medical services, do not contain continuously-released hormones, and can be used only when needed - at the time of coitus. Unfortunately, the only coitally-dependent contraceptives currently available are 1) male or female condoms which are often avoided because they are difficult or uncomfortable to use. And 2) spermicides containing nonoxynol-9 which is cytotoxic, causes significant tissue irritation, and may even increase risk of acquiring HIV. PPCM has already received extensive preclinical evaluation by several major laboratories and consistently demonstrates an excellent safety profile. PPCM has a novel mechanism and inactivates without being cytotoxic. During this grant we will also address the problem of consumer acceptance of vaginal products by seeking early consumer input on product characteristics. This grant will provide funding necessary to develop an aesthetically acceptable, safe and effective vaginal contraceptive, and complete all preclinical studies required by the FDA for submission of an Investigational New Drug (IND) application. Importantly, PPCM has multi-purpose technology (MPT) potential, and is also under development as an anti-viral drug.
Project Terms: absorption; acrosin; Acrosome; Address; Adverse effects; analytical method; Animals; Applications Grants; base; Binding; Biological Assay; Biological Markers; birth control; Cervical; Characteristics; Chemistry; Clinical Protocols; Clinical Research; Clinical trial protocol document; Clinical Trials; Coitus; Complement; Complex; Contraceptive Agents; contraceptive efficacy; contraceptive practice; Contracts; cost; Cyclic GMP; cytotoxic; Dermal; design; Developed Countries; Development; Dosage Forms; Dose; drug development; drug efficacy; Drug Formulations; drug testing; Effectiveness; efficacy study; Ensure; Esthetics; Evaluation; Feedback; Female Condoms; Formulation; Funding; Future; Gel; genital herpes; Goals; Grant; Guidelines; Health; HIV; Hormones; Human; Hyaluronan; Hyaluronidase; improved; In Vitro; Individual; Infection; Investigational Drugs; Investigational New Drug Application; irritation; Laboratories; Length; Local Lymph Node Assay; Male Condoms; Manufacturer Name; Medical; Methods; Modeling; Modernization; Molecular Weight; Monitor; Mus; Neisseria gonorrhoeae; Nonoxynol 9; novel; novel therapeutics; Oryctolagus cuniculus; particle; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology and Toxicology; Phase; Phase I Clinical Trials; Phase III Clinical Trials; Placebos; Polymers; pre-clinical; preclinical development; preclinical evaluation; preclinical study; Pregnancy; premature; Preventive treatment; product development; programs; Publications; quality assurance; Quality Control; Rattus; Reference Standards; Reporting; Research; Risk; Safety; safety study; Sampling; Sampling Studies; scale up; Science; Services; Simplexvirus; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Sodium; Sodium Chloride; Solid; Sperm Capacitation; sperm cell; Sperm Motility; Spermatocidal Agents; Technology; Time; Tissues; Toxicology; Vagina; Vaginal Douching; Viral; Viscosity; Woman; Work; Writing
