Contraceptive efficacy of norethindrone encapsulated in injectable biodegradable poly-dl-lactide-co-glycolide microspheres (NET-90): Phase III clinical study

Safety, contraceptive efficacy, and acceptability of norethindrone, encapsulated in biodegradable poly-dl-lactide-co-glycolide injectable microspheres (NET-90), was evaluated for 12 months in one hundred women. Fifty-one volunteers received 65 mg, and 49 received 100 mg of NET-90, at three month intervals, intramuscularly in the gluteal region. The mean NET levels at 3-month intervals for the 65 and 100 mg groups were, respectively, 0.32+/-0.16 ng/ml and 0.49+/-0.25 ng/ml. No local or systemic side-effects were observed in either group. Body weight, blood pressure, and laboratory parameters, namely hemoglobin, hematocrit, lipid profile, sequential multichannel autoanalyzer computer profiles (SMAC), as well as PAP smear, remained within normal limits throughout the study in both groups. There was no pregnancy in the 65 mg group; however, one volunteer became pregnant in the 100 mg group. In the 65 mg group, 52.9% of menstrual cycles were normal, 34.5% were amenorrheic, and 12.6% showed prolonged bleeding. In the 100 mg group, 40.6% of the cycles were normal, 52.3% were amenorrheic, and 7.1% had episodes of prolonged bleeding. A total of 40.3% and 36.6% of the cycles showed increased spotting in the 65 and 100 mg group, respectively. Our observations indicate that NET-90 microsphere injectables can provide a safe, efficacious, and acceptable method of contraception.