Contraceptive efficacy of bioabsorbable pellets of norethindrone (NET) as subcutaneous implants: phase II clinical study.

The contraceptive efficacy of norethindrone (NET) fused pellets was evaluated over 12 months in a Phase II clinical study with three and four pellets, each pellet containing 35 mg of NET. Volunteers were healthy, fertile, sexually active women. The release rate of NET from three and four pellets, respectively, was 150.3 +/- 7.2 micrograms and 212.5 +/- 8.6 micrograms NET/day. Following the implantation of NET pellets, serum NET levels did not show any 'burst effect' and were sustained at levels between 0.4 and 0.6 ng NET/ml serum with three pellets and 0.6-0.7 ng NET/ml serum with four pellets. With three and four pellets, respectively, 40% and 27% of the women had normal menstrual cycles; 20% and 14% were amenorrheic; 27% and 37% had mid-menstrual spotting or bleeding; and 13% and 22% had prolonged episodes of bleeding. Cardiovascular, hepatic, and renal functions were normal throughout the study. Ovulation was inhibited in 85% and 92% of the cycles with three and four pellets, respectively. In women using three pellets, two pregnancies occurred, one at the 6th cycle and another at the 12th cycle. In women using four pellets, no pregnancies occurred during the entire period of study.