Contraception
Conditions
Keywords
Estetrol, Drospirenone, Uridine diphosphate glucuronosyltransferase-2B7, Drug-drug interaction, Valproic acid
Brief summary
The present study is designed to determine the effect of valproic acid (VAL), a UGT2B7 inhibiting drug, on the pharmacokinetics (PK) of estetrol (E4)
Detailed description
In the present study, E4/DRSP will be administered alone (Treatment A) and in combination with VAL (Treatment B) following two sequences A-B or B-A.
Interventions
DRUGE4/DRSP
Administered as specified in the treatment arm.
DRUGVAL
Administered as specified in the treatment arm.
Sponsors
Quotient Sciences
Estetra
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy premenopausal, aged 18-45 years (inclusive) at the time of signing informed consent. * For subjects who are sexually active and are of childbearing potential: willing to use a highly effective non-hormonal method of contraception from screening until the follow-up assessment, such as (but not limited to): non-hormonal intra-uterine device (copper IUD), bilateral tubal occlusion, vasectomised partner, or sexual abstinence in a heterosexual relationship; this is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active, they, with their partner, must comply with the contraceptive requirements as stated earlier. * Body weight ≥45 kg, and a body mass index between 18.0 and 30.0 kg/m² (inclusive). * Negative serum pregnancy test at screening and a negative urine pregnancy test at Day -1.
Exclusion criteria
* The use of: * any prescription drugs, including oral or vaginal hormonal contraceptives, from 28 days prior to first dose administration until study completion; * any herbal medication or dietary supplements acting on cytochrome P450 3A4 (CYP3A4) functions (i.e., St John's Wort), from 28 days prior to first dose administration until study completion; * any over-the-counter medication (including paracetamol or dietary supplements (including vitamins and herbal products ), from 14 days prior to first dose administration until study completion. Limited use (i.e., up to 1200 mg/day) of ibuprofen is allowed; * any depot progestogen preparations or an injectable hormonal method of contraception, from 6 months prior to the first dose administration until study completion. * History of hypersensitivity, serious adverse reaction, or existing contraindication to E4, DRSP or VAL, or excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum concentration (Cmax) of E4 | 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A | PK sampling |
| Area under the plasma concentration versus time curve from time 0 to the last determined concentration (AUC0-tdlc) of E4 | 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A | PK sampling |
| Area under the plasma concentration versus time curve from time 0 to infiny (AUC0-inf) of E4 | 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A | PK sampling |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-tdlc of DRSP | 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A | PK sampling |
| AUC0-tdlc of E4-glucuronide metabolites | 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A | PK sampling |
| Number of subjects with adverse events as a measure of safety and tolerability | The total study duration (between 50 and 86 days) | — |
| AUC0-inf of E4-glucuronide metabolites | 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A | PK sampling |
| AUC0-inf of DRSP | 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A | PK sampling |
| Cmax of DRSP | 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A | PK sampling |
| Cmax of E4-glucuronide metabolites | 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A | PK sampling |
Countries
United Kingdom
Outcome results
None listed