Phase 3 study results of drospirenone-only OC

May 5, 2019
Bob Kronemyer

Freelance writer for Contemporary OB/GYN

A fourth-generation progestogen-only pill (POP) with drospirenone may be an effective and safe alternative for women for whom estrogen-based contraceptives are contraindicated.

A fourth-generation progestogen-only pill (POP) with drospirenone (investigational drug LF111, Exeltis) is suitable and effective for the vast majority of women, according to Phase 3 study results.

“I am excited that this will be the first drospirenone-only birth control pill option,” said co-investigator Thomas Kimble, MD, associate dean and assistant professor of ob/gyn at Eastern Virginia Medical School in Norfolk. “Drospirenone is also the first contraceptive progestin derived from spironolactone.”

At the 2019 American College of Obstetricians and Gynecologists annual clinical and scientific meeting in Nashville, Dr. Kimble described several advantages of progestogen-only methods of contraception. “Because these pills do not contain any estrogen ingredients, they are not contraindicated in women with medical comorbidities such as cardiovascular disease,” he told Contemporary OB/GYN. “Thus, these pills can be safely taken by most women with hypertension, lipid disorders or a history of diabetes, as well as those who are obese or smoke.”

Further, POPs are safe for breastfeeding women and can reduce symptoms of premenstrual syndrome and painful periods.

Drospirenone has a pharmacological profile similar to natural progesterone and possesses antimineralocorticoid and antiandrogenic activity. 

“Due to its antimineralocorticoid effect, drospirenone may offer the benefits of reduced fluid retention and weight loss,” Dr. Kimble said.

He estimated that over 90% of reproductive-aged women are candidates for drospirenone, which is a far greater percentage than for any other oral contraception.

“This particular pill also has a much better menstrual cycle bleeding profile compared to other progestogen-only pills,” he said. “We see less breakthrough bleeding and very high tolerability.”

The multicenter, clinical study recruited 993 sexually active women, of whom 915 were 35 years old or younger. 

The regimen was one drospirenone pill daily for 24 days, followed by a placebo for 4 days. “This schedule was chosen because it was thought that a break in the intake regimen might improve menstrual cycle control,” Dr. Kimble said.

A total of 352 women completed the study, while the remaining 654 terminated early due to multiple factors, including loss to follow-up (n = 269) and citing adverse events (AEs) (n = 113). Among the AEs were nasopharyngitis (7.7%), headache (6.4%), nausea (6.3%), dysmenorrhea (5.8%) and metrorrhagia (5.3%).

The overall Pearl Index (PI) was comparable to that for other birth control pills: 2.4 (95% CI: 1.2-4.2), with over 6,000 exposure cycles and 12 confirmed pregnancies. But for women 35 and under, the PI was 2.7 (95% CI: 1.4 - 4.7), with 5,835 exposure cycles collected and seven pregnancies.

There were no reports of venous thromboembolism, arterial thromboembolism, myocardial infarction, stroke or pulmonary embolism.

“None of the results are surprising because drospirenone has been on the market for a few years now in combined forms of birth control with both an estrogen and a progesterone,” Dr. Kimble said. “Drospirenone has previously been shown to be extremely tolerable and effective.”

However, because drospirenone is a metabolite of spironolactone, women who have hypertension and are on a potassium-sparing diuretic may need to have their potassium levels monitored and should check with their primary care provider.

Dr. Kimble is hopeful that the new formula of drospirenone will become commercially available in the United States within the next year. “This will soon become a first-line contraceptive that is progestin-only and has an efficacy and tolerability similar to that of combined contraceptives,” he said.

Disclosures:

 

Dr. Kimble receives research funding from Exeltis.