Effect of mavoglurant (AFQ056), a selective mGluR5 antagonist, on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and levonorgestrel in healthy women.
OBJECTIVE
To compare the pharmacokinetics (PKs) of a combination oral contraceptive (OC) when given alone or concomitantly with the selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056).


METHODS
This open-label, fixed-sequence, two-period study included 30 healthy female subjects aged 18-40 years. In period 1, a single oral dose of an OC containing 30 μg ethinyl estradiol (EE)/150 μg levonorgestrel (LNG) was administered alone. In period 2, the OC was administered with a clinically relevant multiple dose of mavoglurant 100 mg b.i.d. under steady-state conditions. Plasma concentrations of EE and LNG were measured up to 72 hours post administration, and the PK parameters Cmax and AUClast were estimated using noncompartmental methods.


RESULTS
The geometric mean ratios of EE Cmax and AUClast obtained with and without mavoglurant were 0.97 (90% confidence interval (CI): 0.90-1.06) and 0.94 (90% CI: 0.86-1.03), respectively. The corresponding Cmax and AUClast for LNG were 0.81 (90% CI: 0.75-0.87) and 0.68 (90% CI: 0.63-0.73), respectively.


CONCLUSIONS
In conclusion, EE PK was unchanged, whereas Cmax and AUClast of LNG were 19% and 32% lower, respectively, when given with mavoglurant Further investigation regarding the impact on contraceptive efficacy is warranted.
Rama
R
Sivasubramanian
Abhijit
A
Chakraborty
Marie-Laure
ML
Rouzade-Dominguez
Srikanth
S
Neelakantham
Annamaria
A
Jakab
Tjeert
T
Mensinga
Eric
E
Legangneux
Ralph
R
Woessner
Mike
M
Ufer
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors*; D055815:Young Adult
D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; C578935:GRM5 protein, human; D007211:Indoles; D064529:Receptor, Metabotropic Glutamate 5; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; C581397:mavoglurant