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

Contraception Clinical Trial

Official title:

An Open-label, Two-way Cross-over Study to Determine the Effect of Multiple Doses of Valproic Acid on the Pharmacokinetics and Safety of a Single Oral Dose of Estetrol/Drospirenone in Healthy Female Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03512860
• Other study ID #: MIT-Es0001-C110
• Secondary ID: 2017-004280-12
• Status: Completed
• Phase: Phase 1
• Start date: April 12, 2018
• Est. completion date: October 8, 2018

Study information

• Verified date: December 2018
• Source: Estetra
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 8, 2018
• Est. primary completion date: October 8, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Contraception

Intervention

Drug:
• E4/DRSP
Administered as specified in the treatment arm.
• VAL
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
United Kingdom	Quotient Sciences	Ruddington	Nottingham

Sponsors (2)

Lead Sponsor	Collaborator
Estetra	Quotient Sciences

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum concentration (Cmax) of E4	PK sampling	0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
Primary	Area under the plasma concentration versus time curve from time 0 to the last determined concentration (AUC0-tdlc) of E4	PK sampling	0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
Primary	Area under the plasma concentration versus time curve from time 0 to infiny (AUC0-inf) of E4	PK sampling	0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
Secondary	Number of subjects with adverse events as a measure of safety and tolerability		The total study duration (between 50 and 86 days)
Secondary	Cmax of DRSP	PK sampling	0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
Secondary	Cmax of E4-glucuronide metabolites	PK sampling	0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
Secondary	AUC0-tdlc of DRSP	PK sampling	0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
Secondary	AUC0-tdlc of E4-glucuronide metabolites	PK sampling	0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
Secondary	AUC0-inf of DRSP	PK sampling	0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
Secondary	AUC0-inf of E4-glucuronide metabolites	PK sampling	0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A