Drug Drug InteractionPhase 1NCT06799884
A Drug-drug Interaction Trial in Healthy Female Participants to Investigate the Effect of Aprocitentan on Combined Hormonal Contraceptives
A Phase 1 study testing Ethinyl Estradiol / Levonorgestrel Oral Tablet and Aprocitentan in people with Drug Drug Interaction, run by Idorsia Pharmaceuticals Ltd. at 1 site in Czechia.
Trial summary
The goal of this clinical trial is to learn if drug aprocitentan has an effect on hormonal contraceptives in healthy female volunteers. The main question it aims to answer is: Does aprocitentan modify the fate of hormonal contraceptives in the body? Trial participants will: Take a single dose of hormonal… Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Drug Drug Interaction
- What is being tested?
- Ethinyl Estradiol / Levonorgestrel Oral Tablet and Aprocitentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteCzechia
- Study dates
- 18 Jan 2025to 21 Feb 2025
- 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 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Signed and dated informed consent form (ICF) prior to any trial-mandated procedure.
- Healthy female participants aged from 18 to 65 years at the time of signing the ICF.
- Ability to communicate well with the investigator, in a language understandable to the participant, and to understand and comply with the trial requirements.
- Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at Screening.
- Normal or not clinically significant abnormal systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 45-90 bpm (inclusive), measured on either arm, after 5 min in the supine position at Screening and on Day 1 (predose) of Trial Period A (TP A).
- Participant of childbearing potential who has a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 (predose) of TP A.
- Participant of childbearing potential who agrees to use two reliable methods of non- hormonal contraception from Screening and for at least 30 days after the last trial intervention administration, or be sexually inactive, or have a vasectomized partner.
- Participant of non-childbearing potential, i.e., postmenopausal (defined as 12 consecutive months with no menses without an alternative medical cause, confirmed by an follicle stimulating hormone test), with previous bilateral salpingectomy, bilateral salpingo-oophorectomy, or hysterectomy, or with premature ovarian failure (confirmed by a specialist), XY genotype, Turner syndrome, uterine agenesis).
Who cannot join
- Known hypersensitivity to aprocitentan, ethinylestradiol, or levonorgestrel, or treatments of the same class, or any of their excipients.
- Clinically relevant findings on the physical examination at Screening.
- Clinically relevant abnormalities on 12-lead electrocardiogram (ECG), measured after 5 min in a supine position at Screening or on Day 1 (pre-dose) of TP A.
- Clinically relevant findings in clinical laboratory tests (hematology and clinical chemistry) at Screening.
- History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the trial interventions (appendectomy and herniotomy allowed if performed > 12 weeks prior to first trial intervention administration, cholecystectomy not allowed).
- Acute, ongoing, recurrent, or chronic systemic disease able to interfere with the evaluation of the trial results.
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- Previous clinically relevant history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
- Previous therapy with hormonal contraceptives or hormone replacement therapy within 2 months prior to first trial intervention administration.
- Pregnant, planning to become pregnant during the trial, or lactating participant of childbearing potential.
- Participant presenting any contraindications for LOETTE®
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-center, Open-label, Fixed-sequence Trial to Investigate the Effect of Multiple-dose Aprocitentan on the Single-dose Pharmacokinetics of Combined Oral Contraceptives in Healthy Female Participants
The goal of this clinical trial is to learn if drug aprocitentan has an effect on hormonal contraceptives in healthy female volunteers. The main question it aims to answer is:
Does aprocitentan modify the fate of hormonal contraceptives in the body?
Trial participants will:
- Take a single dose of hormonal contraceptives (fixed combination) alone
- Take aprocitentan every day for 2 weeks
- Take a single dose of the same hormonal contraceptives at the same time as the 10th administration of aprocitentan.
Read the detailed description
The main objective of the trial is to evaluate the influence of aprocitentan at steady-state on the single-dose pharmacokinetics (PK) of combined oral contraceptives.
19 healthy female participants will be enrolled to have at least 16 evaluable participants.
Following a screening period (from full signature of the informed consent form [ICF] to enrollment; 10 to 28 days prior to first trial intervention administration), eligible participants (meeting all inclusion criteria and none of the exclusion criteria) will be enrolled in the trial to participate in two sequential trial periods, Trial Period A and Trial Period B, with an in-between period of at least 7 days. Trial Period B will be split into two sequential sub-periods, Trial Period B1 and Trial Period B2.
- Trial Period A: Starts with a single administration of trial intervention on Day 1 and ends with an End-of-Trial Period (EoTP) assessment on Day 5. Trial intervention administration on Day 1 will be followed by a 96-hour observation period for safety monitoring and PK sampling.
- Trial Period B1: Trial intervention will be administered from Day 1 to Day 9, with assessments for PK sampling and safety monitoring performed throughout.
- Trial Period B2: Starts with administration of trial intervention on Day 10 and ends with an EoTP assessment on Day 14. Trial intervention will be administered from Day 10 to Day 13, with assessments for PK sampling and safety monitoring performed throughout.
Trial participation of an individual participant ends with the completion of the Participant Last Visit, which will be performed 10-14 days after the last administration of trial intervention. A post-trial safety follow up is performed 30-40 days after last administration of trial intervention.
- Conditions
- Drug Drug Interaction
- Being tested
- Ethinyl Estradiol / Levonorgestrel Oral Tablet, Aprocitentan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ethinyl Estradiol / Levonorgestrel Oral TabletDrug
Also called LOETTE
Coated tablet of 20 µg ethinyl estradiol and 100 µg levonorgestrel
AprocitentanDrug
Film-coated tablet of aprocitentan 25 mg
| Study group | Role | What they receive |
|---|---|---|
| Ethinyl estradiol/levonorgestrel (LOETTE) | Experimental | In Trial Period A, participants will receive a single oral dose of 20µg ethinyl estradiol/100 µg levonorgestrel in the morning of Day 1. Receives: Drug: Ethinyl Estradiol / Levonorgestrel Oral Tablet |
| Aprocitentan | Experimental | In Trial Period B1, participants will receive a once daily oral dose of 25 mg aprocitentan in the morning of Day 1 to Day 9. Receives: Drug: Aprocitentan |
| Aprocitentan and ethinyl estradiol/levonorgestrel (LOETTE) | Experimental | In Trial Period B2, participants will receive a once daily oral dose of 25 mg aprocitentan in the morning of Day 10 to Day 13.
On Day 10, participants will receive a single oral dose of 20µg ethinyl estradiol/100 µg levonorgestrel, administered concomitantly to aprocitentan. Receives: Drug: Ethinyl Estradiol / Levonorgestrel Oral Tablet; Drug: Aprocitentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum plasma concentration (Cmax) of ethinyl estradiol/levonorgestrel
The measured individual plasma concentrations will be used to directly obtain Cmax.
Measured: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)
Time to maximum plasma concentration (tmax) of ethinyl estradiol/levonorgestrel
The measured individual plasma concentrations will be used to directly obtain tmax.
Measured: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)
Area under the Plasma Concentration-Time Curve (AUC 0-t) of ethinyl estradiol/levonorgestrel
Change to AUC 0-t will be derived by non compartmental analysis of the concentration-time profiles.
Measured: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)
Area under the Plasma Concentration-Time Curve (AUC 0-infinity) of ethinyl estradiol/levonorgestrel
Change to AUC 0-infinity will be derived by non compartmental analysis of the concentration-time profiles.
Measured: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)
Terminal half-life (t1/2) of ethinyl estradiol/levonorgestrel
t1/2 will be derived by non compartmental analysis of the concentration-time profiles.
Measured: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)
Trough plasma concentration (Ctrough) of aprocitentan
Ctrough will be based on measured individual plasma concentrations of aprocitentan.
Measured: Prior to administration on Day 10, 11, 12 and 13 in TP B2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2025
- Study start18 Jan 2025
- Primary completion21 Feb 2025
- Study completion21 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug Drug InteractionStudies 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Idorsia Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06799884
- Sponsor's protocol ID
- ID-080-111
- Other IDs
- 2024-517224-19-00
- Status last verified
- Mar 2025
- First submitted
- 14 Jan 2025
- Last updated
- 11 Mar 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Open-label, Fixed-sequence Trial to Investigate the Effect of Multiple-dose Aprocitentan on the Single-dose Pharmacokinetics of Combined Oral Contraceptives in Healthy Female Participants
- ClinicalTrials.gov ID
- NCT06799884
- Acronym / sponsor ID
- ID-080-111
- Conditions
- Drug Drug Interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 18 Jan 2025 (actual)
- Primary completion
- 21 Feb 2025 (actual)
- Study completion
- 21 Feb 2025 (actual)
- First posted
- 29 Jan 2025 (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 goal of this clinical trial is to learn if drug aprocitentan has an effect on hormonal contraceptives in healthy female volunteers. The main question it aims to answer is:
Does aprocitentan modify the fate of hormonal contraceptives in the body?
Trial participants will:
- Take a single dose of hormonal contraceptives (fixed combination) alone
- Take aprocitentan every day for 2 weeks
- Take a single dose of the same hormonal contraceptives at the same time as the 10th administration of aprocitentan.
Detailed description
The main objective of the trial is to evaluate the influence of aprocitentan at steady-state on the single-dose pharmacokinetics (PK) of combined oral contraceptives.
19 healthy female participants will be enrolled to have at least 16 evaluable participants.
Following a screening period (from full signature of the informed consent form [ICF] to enrollment; 10 to 28 days prior to first trial intervention administration), eligible participants (meeting all inclusion criteria and none of the exclusion criteria) will be enrolled in the trial to participate in two sequential trial periods, Trial Period A and Trial Period B, with an in-between period of at least 7 days. Trial Period B will be split into two sequential sub-periods, Trial Period B1 and Trial Period B2.
- Trial Period A: Starts with a single administration of trial intervention on Day 1 and ends with an End-of-Trial Period (EoTP) assessment on Day 5. Trial intervention administration on Day 1 will be followed by a 96-hour observation period for safety monitoring and PK sampling.
- Trial Period B1: Trial intervention will be administered from Day 1 to Day 9, with assessments for PK sampling and safety monitoring performed throughout.
- Trial Period B2: Starts with administration of trial intervention on Day 10 and ends with an EoTP assessment on Day 14. Trial intervention will be administered from Day 10 to Day 13, with assessments for PK sampling and safety monitoring performed throughout.
Trial participation of an individual participant ends with the completion of the Participant Last Visit, which will be performed 10-14 days after the last administration of trial intervention. A post-trial safety follow up is performed 30-40 days after last administration of trial intervention.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ethinyl estradiol/levonorgestrel (LOETTE) | Experimental | Drug: Ethinyl Estradiol / Levonorgestrel Oral TabletIn Trial Period A, participants will receive a single oral dose of 20µg ethinyl estradiol/100 µg levonorgestrel in the morning of Day 1. |
| Aprocitentan | Experimental | Drug: AprocitentanIn Trial Period B1, participants will receive a once daily oral dose of 25 mg aprocitentan in the morning of Day 1 to Day 9. |
| Aprocitentan and ethinyl estradiol/levonorgestrel (LOETTE) | Experimental | Drug: Ethinyl Estradiol / Levonorgestrel Oral Tablet, Drug: AprocitentanIn Trial Period B2, participants will receive a once daily oral dose of 25 mg aprocitentan in the morning of Day 10 to Day 13. On Day 10, participants will receive a single oral dose of 20µg ethinyl estradiol/100 µg levonorgestrel, administered concomitantly to aprocitentan. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Signed and dated informed consent form (ICF) prior to any trial-mandated procedure.
- Healthy female participants aged from 18 to 65 years at the time of signing the ICF.
- Ability to communicate well with the investigator, in a language understandable to the participant, and to understand and comply with the trial requirements.
- Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at Screening.
- Normal or not clinically significant abnormal systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 45-90 bpm (inclusive), measured on either arm, after 5 min in the supine position at Screening and on Day 1 (predose) of Trial Period A (TP A).
Key exclusion criteria (10 listed)
- Known hypersensitivity to aprocitentan, ethinylestradiol, or levonorgestrel, or treatments of the same class, or any of their excipients.
- Clinically relevant findings on the physical examination at Screening.
- Clinically relevant abnormalities on 12-lead electrocardiogram (ECG), measured after 5 min in a supine position at Screening or on Day 1 (pre-dose) of TP A.
- Clinically relevant findings in clinical laboratory tests (hematology and clinical chemistry) at Screening.
- History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the trial interventions (appendectomy and herniotomy allowed if performed > 12 weeks prior to first trial intervention administration, cholecystectomy not allowed).
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 |
|---|---|---|
| Ethinyl Estradiol / Levonorgestrel Oral TabletAlso: LOETTECoated tablet of 20 µg ethinyl estradiol and 100 µg levonorgestrel | Drug | Aprocitentan and ethinyl estradiol/levonorgestrel (LOETTE), Ethinyl estradiol/levonorgestrel (LOETTE) |
| AprocitentanFilm-coated tablet of aprocitentan 25 mg | Drug | Aprocitentan, Aprocitentan and ethinyl estradiol/levonorgestrel (LOETTE) |
Primary outcome
Maximum plasma concentration (Cmax) of ethinyl estradiol/levonorgestrel
Time frame: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)
The measured individual plasma concentrations will be used to directly obtain Cmax.
Time to maximum plasma concentration (tmax) of ethinyl estradiol/levonorgestrel
Time frame: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)
The measured individual plasma concentrations will be used to directly obtain tmax.
Area under the Plasma Concentration-Time Curve (AUC 0-t) of ethinyl estradiol/levonorgestrel
Time frame: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)
Change to AUC 0-t will be derived by non compartmental analysis of the concentration-time profiles.
Area under the Plasma Concentration-Time Curve (AUC 0-infinity) of ethinyl estradiol/levonorgestrel
Time frame: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)
Change to AUC 0-infinity will be derived by non compartmental analysis of the concentration-time profiles.
Terminal half-life (t1/2) of ethinyl estradiol/levonorgestrel
Time frame: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)
t1/2 will be derived by non compartmental analysis of the concentration-time profiles.
Trough plasma concentration (Ctrough) of aprocitentan
Time frame: Prior to administration on Day 10, 11, 12 and 13 in TP B2
Ctrough will be based on measured individual plasma concentrations of aprocitentan.
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 11 Mar 2025.
- Individual participant dataSharing planned: No
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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.
Clinical Trials study director
Idorsia Pharmaceuticals
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 Ethinyl Estradiol / Levonorgestrel Oral Tablet and Aprocitentan in people with Drug Drug Interaction, run by Idorsia Pharmaceuticals Ltd. at 1 site in Czechia.
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 8 inclusion and 10 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 11 Mar 2025. 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 Czechia. 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 plasma concentration (Cmax) of ethinyl estradiol/levonorgestrel (time frame: TP A: On Day 1 (pre-dose) and predefined times up to 96 hours post-dose (Day 5); TP B2: On Day 10 (pre-dose) and predefined times up to 96 hours post-dose (Day 14)). The study lists 6 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 11 Mar 2025.