General Information

Natazia is specifically indicated for the the following:

for use by women to prevent pregnancy

the treatment of heavy menstrual bleeding in women without organic pathology who choose to use an oral contraceptive as their method of contraception

Natazia is supplied as a series of tablets for oral administration. Natazia should be started on Day 1 of the menstrual cycle (the first day of menstrual bleeding). One tablet should be taken orally at the same time every day. Tablets must be taken in the order directed on the blister pack. Tablets should not be skipped or intake delayed by more than 12 hours.

Mechanism of Action

Natazia is a combined oral contraceptive that contains an estrogen called estradiol valerate in combination with a progestogen called dienogest. Estradiol valerate is converted to estradiol which is the same estrogen produced in a woman’s body. It has a unique dosing approach with four progestin/estrogen dosing combinations which have been designed to deliver hormones in a novel four-phase estrogen step-down, progestin step-up regimen.

Indication 1 -the prevention of pregnancy

approved May 2010

Clinical Trial Results

The FDA approval of Natazia was based on two multicenter phase III clinical trials in North America and Europe. The Pearl Index (PI) was the primary efficacy endpoint used to assess contraceptive reliability and was assessed in each the two studies, assuming all subjects were at risk of pregnancy unless a back-up contraceptive was used. The PI is based on pregnancies that occurred after the onset of treatment and within 7 days after the last pill intake.

North America: This trial enrolled 490 healthy subjects between 18 and 35 years of age with a mean weight of 62.5 kg and a mean BMI of 23.3 kg/m2. The subjects were treated for up to 28 cycles of 28 days each. There were 5 pregnancies within 13 Cycles and 7 days after last treatment. The estimated PI for the North American study was 1.64 and the contraceptive failure rate at the end of the first year was 0.016.

European Study (Germany, Austria and Spain): This study enrolled 1,377 healthy subjects between the ages of 18 and 50 years with an mean weight of 63.8 kg and a mean BMI of 22.8 kg/m2. The subjects were treated for 20 cycles of 28 days each. There were 9 pregnancies within 13 Cycles and 7 days after last treatment. The estimated PI for the European study was 1.04 and the contraceptive failure rate at the end of the first year was 0.010.

Indication 2 - heavy menstrual bleeding

approved March 2012

Clinical Trial Results

The FDA approval of Natazia for heavy menstrual bleeding was based on two identically-designed, multicenter, double-blind, randomized, placebo controlled trials, one in North America and one in Europe and Australia. The studies enrolled a total of 421 adult women with a diagnosis of dysfunctional uterine bleeding characterized as heavy, prolonged and/or frequent bleeding without organic pathology. Heavy menstrual bleeding was defined as menstrual blood loss of 80 mL or more in at least two bleeding episodes during a 90-day run in phase. Subjects were treated for seven 28-day cycles with either Natazia or placebo. The proportion of the intent-to-treat subjects with complete symptom relief (based on 8 strictly defined criteria during the 90-day efficacy assessment phase) was 29.2% in the Natazia group compared to 2.9% in the placebo group in the first study and 29.5% in the Natazia group compared to 1.2% in the placebo group in the second study. The subjects who received Natazia achieved a statistically significant reduction in menstrual blood loss compared with subjects who received placebo.