ContraceptionPhase 1NCT03512860
Estetrol (E4)/Drospirenone (DRSP) Drug-drug Interaction (DDI) Study
A Phase 1 study testing E4/DRSP and VAL in people with Contraception, run by Estetra at 1 site in United Kingdom.
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) Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception
- What is being tested?
- E4/DRSP and VAL
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Apr 2018to 8 Oct 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United Kingdom1 site
Quotient Sciences
Ruddington, Nottingham, NG11 6JS
About this study
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
The present study is designed to determine the effect of valproic acid (VAL), a UGT2B7 inhibiting drug, on the pharmacokinetics (PK) of estetrol (E4)
Read the 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.
- Conditions
- Contraception
- Being tested
- E4/DRSP, VAL
- Keywords
- Estetrol, Drospirenone, Uridine diphosphate glucuronosyltransferase-2B7, Drug-drug interaction, Valproic acid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E4/DRSPDrug
Also called E4 and DRSP combined tablet
Administered as specified in the treatment arm.
VALDrug
Also called Valproic acid, Depakote®
Administered as specified in the treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Drug: E4/DRSP; Drug: VAL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum concentration (Cmax) of E4
PK sampling
Measured: 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
Measured: 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
Measured: 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
Measured: The total study duration (between 50 and 86 days)
Cmax of DRSP
PK sampling
Measured: 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
PK sampling
Measured: 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
PK sampling
Measured: 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
PK sampling
Measured: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
AUC0-inf of DRSP
PK sampling
Measured: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
AUC0-inf of E4-glucuronide metabolites
PK sampling
Measured: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2018
- Study start12 Apr 2018
- Primary completion8 Oct 2018
- Study completion8 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Estetra
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quotient Sciences
- Responsible party
- Sponsor
- Investigators
- Sharan Sidhu, Principal investigator, Quotient Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03512860
- Sponsor's protocol ID
- MIT-Es0001-C110
- Other IDs
- 2017-004280-12, 2017
- Status last verified
- Dec 2018
- First submitted
- 19 Apr 2018
- Last updated
- 14 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03512860
- Acronym / sponsor ID
- MIT-Es0001-C110
- Conditions
- Contraception
- Keywords
- Estetrol, Drospirenone, Uridine diphosphate glucuronosyltransferase-2B7, Drug-drug interaction, Valproic acid
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- EstetraIndustry (pharma, biotech, devices)
- Collaborators
- Quotient Sciences
- Study start
- 12 Apr 2018 (actual)
- Primary completion
- 8 Oct 2018 (actual)
- Study completion
- 8 Oct 2018 (actual)
- First posted
- 1 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| E4/DRSP (Treatment A) - E4/DRSP + VAL (Treatment B) | Experimental | Drug: E4/DRSP, Drug: VALSequence 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. |
| E4/DRSP + VAL (Treatment B) - E4/DRSP (Treatment A) | Experimental | Drug: E4/DRSP, Drug: VALSequence 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). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- The use of:
- History of hypersensitivity, serious adverse reaction, or existing contraindication to E4, DRSP or VAL, or excipients.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E4/DRSPAlso: E4 and DRSP combined tabletAdministered as specified in the treatment arm. | Drug | E4/DRSP (Treatment A) - E4/DRSP + VAL (Treatment B), E4/DRSP + VAL (Treatment B) - E4/DRSP (Treatment A) |
| VALAlso: Valproic acid, Depakote®Administered as specified in the treatment arm. | Drug | E4/DRSP (Treatment A) - E4/DRSP + VAL (Treatment B), E4/DRSP + VAL (Treatment B) - E4/DRSP (Treatment A) |
Primary outcome
Maximum concentration (Cmax) of E4
Time frame: 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
Time frame: 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
Time frame: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
PK sampling
7 secondary outcomes
Number of subjects with adverse events as a measure of safety and tolerability
Time frame: The total study duration (between 50 and 86 days)
Cmax of DRSP
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
AUC0-inf of DRSP
Time frame: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
AUC0-inf of E4-glucuronide metabolites
Time frame: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sharan Sidhu principal investigator
Quotient Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing E4/DRSP and VAL in people with Contraception, run by Estetra at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum concentration (Cmax) of E4 (time frame: 0-168 hr post E4/DRSP dose in both periods 1 and 2 of the two sequences A-B and B-A). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2018.