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.

Study identifier:D4325C00006

ClinicalTrials.gov identifier:NCT05505162

EudraCT identifier:N/A

CTIS identifier:N/A

Recruitment Complete

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

Medical condition

Healthy Female Participants

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Zibotentan, EE/LNG

Sex

Female

Actual Enrollment

Study type

Interventional

Age

35 Years - 75 Years

Date

Study Start Date: 24 Aug 2022

Estimated Primary Completion Date: 26 Dec 2022

Estimated Study Completion Date: 26 Dec 2022

Study design

Allocation: N/A
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2022 by AstraZeneca

Collaborators

PAREXEL

Inclusion and exclusion criteria

Inclusion Criteria

- 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:
(i) 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].
(ii) 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.

Exclusion Criteria

- 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:
(i) 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.
- 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:
(i) 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:
(i) Positive COVID-19 test result on check in into the clinical unit on Day -1 and on Day 14.
(ii) 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.
(iii) Previously hospitalized with COVID-19 infection within the last 3 months prior to the screening visit.

No locations available

Arms	Assigned Interventions
Experimental: Zibotentan and EE/LNG 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).	-

Arms

Assigned Interventions

Experimental: Zibotentan and EE/LNG
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).

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]