Clinical evaluation of drugs used in fertility regulation
Siemens, A.J.
Human Reproduction 1(6): 405-410
1986
ISSN/ISBN: 0268-1161 PMID: 3104401 DOI: 10.1093/oxfordjournals.humrep.a136436Document Number: 349742
The nature of clinical studies in Phases I to III of various drugs used in contraception, including Norplant implants, are described. International ethical standards generally agree that subjects should give informed consent before entering a study. Study subjects in Phase I of clinical evaluation are generally normal human volunteers who meet very specific selection guidelines. In special cases a target population of patients might be studied. Typically, the number of subjects studied in this phase ranges from 20-80 depending upon the specific product and the specific study objectives. The primary purpose of Phase I studies is to determine the acute toxicity potential of the product. In addition, one may want to determine the pharmacological or metabolic effects of the product. Family Health International (FHI) currently is planning the development of a new vaginal contraceptive product (FD 100). Initial studies will focus on safety parameters associated with the vaginal route. A subsequent Phase I study of FD 100 will provide an initial assessment of efficacy as well as safety. Phase II studies typically provide an opportunity to examine issues of efficacy and safety in a clinical target population and often permit a determination of the dose and dose intervals which will be most appropriate for that particular population and allow for a more definitive evaluation of the pharmacokinetics and, perhaps, bioavailability of a particular formulation. Typically, between 50-200 subjects are enrolled in a series of Phase II studies. The Program for Applied Research on Fertility Regulation and FHI recently have conducted a Phase II evaluation of a norethindrone (NET) pellet implant system. The most important side effect associated with this implant system consisted of changes in menstrual patterns. The Norplant subdermal implant system is in advanced stages of Phase III evaluation in the US and in selected other countries. In all study countries, the principal investigators are specialists in obstetrics and gynecology and the implants are offered to 400-600 healthy, nonlactating women who want to limit their family size. Beyond a typical study of product safety and efficacy, the novel nature of this implant technology has required the incorporation of special approaches into the multinational Phase III evaluation of the Norplant system. The Today-TM contraceptive sponge was approved for marketing by the Food and Drug Administration in 1983 based largely upon a multicenter study conducted by FHI in the US.