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

NCT03512860 | Completed Phase 1

• 2 other identifiers: MIT-Es0001-C1102017-004280-12
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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)

Conditions

Contraception

Keywords

Estetrol; Drospirenone; Uridine diphosphate glucuronosyltransferase-2B7; Drug-drug interaction; Valproic acid

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (7)

• Number of subjects with adverse events as a measure of safety and tolerability

  The total study duration (between 50 and 86 days)

• 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

• 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

• 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

• 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

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: E4/DRSP; Drug: VAL

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

EXPERIMENTAL

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).

Drug: E4/DRSP; Drug: VAL

Interventions

E4/DRSP DRUG

Administered as specified in the treatment arm.

Also known as: E4 and DRSP combined tablet

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

VAL DRUG

Administered as specified in the treatment arm.

Also known as: Valproic acid, Depakote®

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

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Estetra: lead
• Quotient Sciences: collaborator

Study Sites (1)

Quotient Sciences

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

Valproic Acid

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Sharan Sidhu

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2018
• First Posted: May 1, 2018
• Study Start: April 12, 2018
• Primary Completion: October 8, 2018
• Study Completion: October 8, 2018
• Last Updated: December 14, 2018

Record last verified: 2018-12

Locations

GB (1)