Long-term efficacy and safety of a monophasic combined oral contraceptive containing 0.02 mg ethinylestradiol and 2 mg chlormadinone acetate administered in a 24/4-day regimen.
OBJECTIVE
This study was conducted to assess the long-term efficacy and safety of a low-dose monophasic combined oral contraceptive (COC) containing 0.02 mg ethinylestradiol (EE) and 2 mg chlormadinone acetate (CMA) in a novel regimen administered daily for 24 days followed by a 4-day placebo interval.


METHODS
In this multicenter, uncontrolled, Phase III trial, 1665 subjects took the COC 0.02 mg EE/2 mg CMA for up to 21 cycles. The overall Pearl Index was the primary end point; cycle control, safety, effect on acne and seborrhea, and changes in body weight and libido were secondary end points.


RESULTS
Contraceptive efficacy was analyzed for 1653 subjects completing 21,495 cycles. Six pregnancies occurred during trial duration with one attributable to method failure. The overall Pearl Index for the first year of use was 0.33 (95% confidence interval, 0.09-0.85). The mean number of bleeding/spotting days during six 90-day reference periods (RPs) decreased from 17.0 (RP 1) to 11.7 (RP 6), and the number of bleeding episodes per RP decreased from 3.8 (RP 1) to 2.7 (RP 6). Among subjects who presented with acne at the baseline visit, a decrease of papules/pustules and comedones was observed during the course of the trial. The most common "at least possibly related" adverse events were headache, breast discomfort and nausea. The tolerability and well-being was reported as being excellent or good in the majority of trial subjects (84.6% and 80.2%, respectively).


CONCLUSIONS
The low-dose COC 0.02 mg EE/2 mg CMA administered daily for 24 days followed by a 4-day placebo interval provides high contraceptive efficacy combined with an adequate cycle control and safety profile, beneficial effects on acne, and is well tolerated.
Brucker
Cosima
C
Klinikum Nürnberg Nord, Klinik für Frauenheilkunde, Prof.-Ernst-Nathan-Str. 1, Nürnberg, Germany. cosima.brucker@klinikum-nuernberg.de
Hedon
Bernard
B
The
Hok Sien
HS
Höschen
Kornelia
K
Binder
Natascha
N
Christoph
Annette
A
D000152:Acne Vulgaris / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D001835:Body Weight / Q000187:drug effects; D002715:Chlormadinone Acetate / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D012628:Dermatitis, Seborrheic / Q000188:drug therapy; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004412:Dysmenorrhea / Q000139:chemically induced / Q000188:drug therapy; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007989:Libido / Q000187:drug effects; D008597:Menstrual Cycle / Q000187:drug effects; D034445:Ovulation Inhibition / Q000187:drug effects*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003277:Contraceptives, Oral, Combined; D003879:Dermatologic Agents; D014280:Triglycerides; D002715:Chlormadinone Acetate; D004997:Ethinyl Estradiol; D002784:Cholesterol