Estetrol (E4)/Drospirenone (DRSP) Drug-drug Interaction (DDI) Study

Estetra

Status and phase: Completed; Phase 1

Conditions: Contraception

Treatments: Drug: E4/DRSP; Drug: VAL

Study type: Interventional

Funder types: Industry

Identifiers

NCT03512860

MIT-Es0001-C110

2017-004280-12 (EudraCT Number)

Details and patient eligibility

About

The present study is designed to determine the effect of valproic acid (VAL), a UGT2B7 inhibiting drug, on the pharmacokinetics (PK) of estetrol (E4)

Full 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.

Enrollment: 24 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

E4/DRSP (Treatment A) - E4/DRSP + VAL (Treatment B)

Experimental group

Description:

Sequence A-B: A single oral dose of E4 combined with DRSP (Treatment A) will be administered during the Period 1. After a washout, subjects will enter into the Period 2. They will receive the Treatment B which consists in multiple oral doses of VAL for 12 consecutive days and one single oral dose of E4/DRSP on Day 5 of the VAL administration.

Treatment:

Drug: VAL

Drug: E4/DRSP

E4/DRSP + VAL (Treatment B) - E4/DRSP (Treatment A)

Experimental group

Description:

Sequence B-A: During Period 1, subjects will receive the Treatment B (multiple oral doses of VAL for 12 consecutive days and one single oral dose of E4/DRSP on Day 5 of the VAL administration) . After a washout, subjects will enter into the Period 2 and receive the Treatment A (a single oral dose of E4 combined with DRSP).

Treatment:

Drug: VAL

Drug: E4/DRSP