Healthy Female ParticipantsPhase 1NCT05505162
Assessing the Effect of Multiple Doses of Zibotentan on the Pharmacokinetics of Single Doses of Combined Oral Contraceptives in Healthy Female Participants of Non-childbearing Potential.
A Phase 1 study testing Zibotentan and EE/LNG in people with Healthy Female Participants, run by AstraZeneca at 1 site in United States.
Trial summary
A study to assess the Pharmacokinetics (PK) of combined oral ethinyl estradiol (EE) and levonorgestrel (LNG) in healthy female participants of non-child-bearing potential, when administered alone and in combination with multiple oral doses of zibotentan. Read more about this study
- Who is it for?
- Ages 35 to 75 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Female Participants
- What is being tested?
- Zibotentan and EE/LNG
- 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 States
- Study dates
- 24 Aug 2022to 10 Jan 2023
- 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 35 to 75 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the protocol.
- Healthy female participants aged 35 to 75 years (inclusive) at Day -1 with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and within 24 hours prior to dosing with EE/LNG on Day 1 and Day 15, must not be lactating and must be of non childbearing potential, confirmed at screening by fulfilling one of the following criteria:
- Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the postmenopausal range [FSH > 40 mIU/mL].
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
- Have a body mass index (BMI) between 18.5 and 35 kg/m2 inclusive at Day -1.
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study. Clinically significant diseases or disorders also include, but are not limited to:
- Undiagnosed abnormal uterine bleeding, (ii) Current diagnosis of, or history of breast cancer, which may be hormone sensitive, (iii) Liver tumors, benign or malignant, or liver disease. Acute viral hepatitis, or severe (decompensated) cirrhosis or use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for alanine aminotransferase (ALT) elevations.
- Sex hormone therapy within 1 month before study.
- Current diagnosis or history of arterial or venous thrombosis (eg, deep vein thrombosis (DVT), pulmonary embolism (PE)), or known heredity risk factors (eg, activated protein C resistance), or coronary artery disease.
- Have inherited or acquired hypercoagulopathy.
- Participants treated with strong or moderate Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 3 months or longer (5 half-lives) prior to first administration of IMP in this study.
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- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any laboratory values with the following deviations:
- Alanine aminotransferase > Upper limit of normal (ULN) (ii) Aspartate aminotransferase > ULN (iii) estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (iv) Creatinine > 1.5 ULN (v) White blood cell count < 3.5 x 109/L (vi) Hemoglobin < lower limit of normal (LLN)
- Prolonged QT interval (QTcF > 470 ms) on ECG at check in into the clinical unit on Day 1 of Treatment Period 1, known congenital long QT syndrome or history of QT prolongation associated with other medications.
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to zibotentan.
- Participants who have received zibotentan within 1 month prior to Day 1 dosing.
- Any of the following signs or confirmation of COVID-19 infection:
- Positive COVID-19 test result on check in into the clinical unit on Day -1 and on Day 14.
- Clinical signs and symptoms consistent with COVID-19 (eg, fever, dry cough, dyspnoea, sore throat, and fatigue) on check in into the clinical unit on Day 1.
- Previously hospitalized with COVID-19 infection within the last 3 months prior to the screening visit.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label, Single-Sequence Study to Assess the Effect of Multiple Doses of Zibotentan on the Pharmacokinetics of Single Doses of Combined Oral Ethinyl Estradiol and Levonorgestrel in Healthy Female Participants of Non-Child-Bearing Potential
A study to assess the Pharmacokinetics (PK) of combined oral ethinyl estradiol (EE) and levonorgestrel (LNG) in healthy female participants of non-child-bearing potential, when administered alone and in combination with multiple oral doses of zibotentan.
Read the detailed description
This is an open-label, single-sequence study conducted at a single study center.
The study will comprise of the following:
- A Screening Period (Visit 1) of maximum 28 days (Day -28 to Day -2).
- Treatment Period 1/Day 1 to Day 5 (in-house stay): Participants will check in at the clinical unit on Day -1 and will be resident at the clinical unit until Day 6.
- Treatment Period 2/Day 6 to Day 14 (home): Outpatient period.
- Treatment Period 3/Day 15 to Day 20 (in-house stay): On the evening of Day 14, the participants will check in at the clinical unit and will be resident at the clinical unit until Day 20.
- A follow-up visit (Day 27) will be conducted 7 days (±2 days) after the last PK sample collection (120 hours post-dose [Day 20]).
Participants will receive two tablets of EE/LNG on days 1 and 15 and 2 capsules of zibotentan on days 6-19.
- Conditions
- Healthy Female Participants
- Being tested
- Zibotentan, EE/LNG
- Keywords
- Ethinyl estradiol, Levonorgestrel, Zibotentan, Chronic Kidney Disease, Non-Child-Bearing Potential, Drug-drug interaction
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZibotentanDrug
Participants will receive two capsules of Zibotentan orally QD from day 6-19.
EE/LNGDrug
Participants will receive two tablets of EE and LNG once on Day 1 and Day 15 as a combined oral dose.
| Study group | Role | What they receive |
|---|---|---|
| Zibotentan and EE/LNG | Experimental | Participants will receive two tablets of combined oral EE/LNG on Day 1 with PK samples obtained from pre-dose on Day 1 until post-dose on Day 6.
Participants will receive two capsules of zibotentan orally QD from Day 6 to Day 14. From Day 15 until Day 19 participants will continue to receive two capsules of zibotentan QD administered orally.
On Day 15, participants will receive two tablets of combined oral EE and LNG with PK samples obtained pre-dose on Day 15 until post-dose (Day 20). Receives: Drug: Zibotentan; Drug: EE/LNG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under plasma concentration time curve from zero to infinity (AUCinf)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Measured: Day 1 and Day 15
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Measured: Day 1 and Day 15
Maximum observed plasma (peak) drug concentration (Cmax)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Measured: Day 1 and Day 15
Terminal elimination half-life (t1/2λz)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Measured: Day 1 and Day 15
Time to reach maximum observed concentration (tmax)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Measured: Day 1 and Day 15
Apparent total body clearance of drug from plasma (CL/F)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Measured: Day 1 and Day 15
Apparent volume of distribution based on terminal phase (Vz/F)
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Measured: Day 1 and Day 15
Secondary outcomes (4)
Area under plasma concentration-time curve in the dose interval (AUCtau)
The PK of zibotentan in healthy female volunteers of non-child-bearing potential will be assessed.
Measured: Day 15
Maximum observed plasma (peak) drug concentration (Cmax)
The PK of zibotentan in healthy female volunteers of non-child-bearing potential will be assessed.
Measured: Day 15
Time to reach maximum observed concentration (tmax)
The PK of zibotentan in healthy female volunteers of non-child-bearing potential will be assessed.
Measured: Day 15
Number of participants with adverse events
The safety and tolerability of zibotentan alone and in combination with combined oral EE and LNG will be examined.
Measured: Until Follow up visit (7 days +/-2 days after last PK sample)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2022
- Study start24 Aug 2022
- Primary completion10 Jan 2023
- Study completion10 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy Female ParticipantsStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05505162
- Sponsor's protocol ID
- D4325C00006
- Status last verified
- Feb 2023
- First submitted
- 16 Aug 2022
- Last updated
- 9 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Single-Sequence Study to Assess the Effect of Multiple Doses of Zibotentan on the Pharmacokinetics of Single Doses of Combined Oral Ethinyl Estradiol and Levonorgestrel in Healthy Female Participants of Non-Child-Bearing Potential
- ClinicalTrials.gov ID
- NCT05505162
- Acronym / sponsor ID
- D4325C00006
- Conditions
- Healthy Female Participants
- Keywords
- Ethinyl estradiol, Levonorgestrel, Zibotentan, Chronic Kidney Disease, Non-Child-Bearing Potential, Drug-drug interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 24 Aug 2022 (actual)
- Primary completion
- 10 Jan 2023 (actual)
- Study completion
- 10 Jan 2023 (actual)
- First posted
- 17 Aug 2022 (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.
A study to assess the Pharmacokinetics (PK) of combined oral ethinyl estradiol (EE) and levonorgestrel (LNG) in healthy female participants of non-child-bearing potential, when administered alone and in combination with multiple oral doses of zibotentan.
Detailed description
This is an open-label, single-sequence study conducted at a single study center.
The study will comprise of the following:
- A Screening Period (Visit 1) of maximum 28 days (Day -28 to Day -2).
- Treatment Period 1/Day 1 to Day 5 (in-house stay): Participants will check in at the clinical unit on Day -1 and will be resident at the clinical unit until Day 6.
- Treatment Period 2/Day 6 to Day 14 (home): Outpatient period.
- Treatment Period 3/Day 15 to Day 20 (in-house stay): On the evening of Day 14, the participants will check in at the clinical unit and will be resident at the clinical unit until Day 20.
- A follow-up visit (Day 27) will be conducted 7 days (±2 days) after the last PK sample collection (120 hours post-dose [Day 20]).
Participants will receive two tablets of EE/LNG on days 1 and 15 and 2 capsules of zibotentan on days 6-19.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zibotentan and EE/LNG | Experimental | Drug: Zibotentan, Drug: EE/LNGParticipants will receive two tablets of combined oral EE/LNG on Day 1 with PK samples obtained from pre-dose on Day 1 until post-dose on Day 6. Participants will receive two capsules of zibotentan orally QD from Day 6 to Day 14. From Day 15 until Day 19 participants will continue to receive two capsules of zibotentan QD administered orally. On Day 15, participants will receive two tablets of combined oral EE and LNG with PK samples obtained pre-dose on Day 15 until post-dose (Day 20). |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the protocol.
- Healthy female participants aged 35 to 75 years (inclusive) at Day -1 with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and within 24 hours prior to dosing with EE/LNG on Day 1 and Day 15, must not be lactating and must be of non childbearing potential, confirmed at screening by fulfilling one of the following criteria:
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
Key exclusion criteria (16 listed)
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study. Clinically significant diseases or disorders also include, but are not limited to:
- Sex hormone therapy within 1 month before study.
- Current diagnosis or history of arterial or venous thrombosis (eg, deep vein thrombosis (DVT), pulmonary embolism (PE)), or known heredity risk factors (eg, activated protein C resistance), or coronary artery disease.
- Have inherited or acquired hypercoagulopathy.
- Participants treated with strong or moderate Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 3 months or longer (5 half-lives) prior to first administration of IMP in this study.
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 |
|---|---|---|
| ZibotentanParticipants will receive two capsules of Zibotentan orally QD from day 6-19. | Drug | Zibotentan and EE/LNG |
| EE/LNGParticipants will receive two tablets of EE and LNG once on Day 1 and Day 15 as a combined oral dose. | Drug | Zibotentan and EE/LNG |
Primary outcome
Area under plasma concentration time curve from zero to infinity (AUCinf)
Time frame: Day 1 and Day 15
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)
Time frame: Day 1 and Day 15
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Maximum observed plasma (peak) drug concentration (Cmax)
Time frame: Day 1 and Day 15
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Terminal elimination half-life (t1/2λz)
Time frame: Day 1 and Day 15
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Time to reach maximum observed concentration (tmax)
Time frame: Day 1 and Day 15
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Apparent total body clearance of drug from plasma (CL/F)
Time frame: Day 1 and Day 15
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
Apparent volume of distribution based on terminal phase (Vz/F)
Time frame: Day 1 and Day 15
The effect of multiple doses of zibotentan on the PK of a single dose of combined oral EE and LNG in healthy female volunteers of non-child-bearing potential will be assessed.
4 secondary outcomes
Area under plasma concentration-time curve in the dose interval (AUCtau)
Time frame: Day 15
Maximum observed plasma (peak) drug concentration (Cmax)
Time frame: Day 15
Time to reach maximum observed concentration (tmax)
Time frame: Day 15
Number of participants with adverse events
Time frame: Until Follow up visit (7 days +/-2 days after last PK sample)
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 9 Feb 2023.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Zibotentan and EE/LNG in people with Healthy Female Participants, run by AstraZeneca at 1 site in United States.
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 7 inclusion and 16 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 9 Feb 2023. 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 States. 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?
Area under plasma concentration time curve from zero to infinity (AUCinf) (time frame: Day 1 and Day 15). The study lists 7 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 9 Feb 2023.