A Study to Assess the Pharmacokinetics and Safety of Different Forms and Formulations of AZD9496 in Healthy Subjects
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: AZD9496 (Reference); AZD9496 Variant A; AZD9496 Variant B; AZD9496 Variant C; AZD9496 Variant D
Intervention description: AZD9496 (Reference); AZD9496 Variant A.; AZD9496 Variant B; AZD9496 Variant C; AZD9496 Variant D
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Breast cancer; Healthy volunteers; Pharmacokinetics; AZD9496; Safety; Tolerability

Summary:

      This is a phase 1 open label single centre study of AZD9496 administered orally in healthy
      volunteers. The study design involves single administration of different forms, formulations
      and doses of AZD9496. The study is designed to investigate these different AZD9496 variants.
      The study will evaluate the pharmacokinetic profiles and the safety and tolerability of the
      different forms, formulations and doses of AZD9496

      This is a fixed sequence study with 5-sequential treatment periods in healthy volunteers.
      Each volunteer will receive 5 single doses of AZD9496 in different forms, formulations and
      doses.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of signed and dated, written informed consent prior to any study specific
             procedures.

          2. Healthy male and/or female subjects aged 18 to 65 years with suitable veins for
             cannulation or repeated venipuncture.

          3. Females must have a negative pregnancy test at screening and on admission to the unit,
             must not be lactating and must be of non-childbearing potential, confirmed at
             screening by fulfilling 1 of the following criteria: Post-menopausal defined as
             amenorrhea for at least 12 months or more following cessation of all exogenous
             hormonal treatments and FSH levels in the post-menopausal range (OR) Documentation of
             irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or
             bilateral salpingectomy, but not tubal ligation

          4. Male subjects aged 18 to 39 years must be vasectomized. Male subjects aged 40 to 65
             years must either be vasectomized or have no intention of fathering a child for a
             period of 6 months after receiving the last dose of IMP.

          5. Have a body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive, and weigh at
             least 50 kg and no more than 100 kg, inclusive.

          6. Values for AST, ALT, TBL, GGT and ALP must be at or below the upper limit of normal
             ranges at screening.

        Exclusion Criteria:

          1. History of any clinically significant disease or disorder which, in the opinion of the
             investigator, may either put the subject at risk because of participation in the
             study, or influence the results or the subject's ability to participate in the study.

          2. History or presence of gastrointestinal (GI), hepatic or renal disease, or any other
             condition known to interfere with absorption, distribution, metabolism, or excretion
             of drugs.

          3. Any clinically significant illness, medical/surgical procedure, or trauma within 4
             weeks of the first administration of IMP.

          4. Previous history of venous or arterial thromboembolism or thrombophilia.

          5. History of endometrial polyps, endometrial cancer, atypical endometrial hyperplasia,
             or other endometrial disorders unless subjects have undergone total hysterectomy and
             there is no evidence of active disease (females only).

          6. Any clinically significant abnormalities in clinical chemistry (other than Inclusion
             no.6), hematology, or urinalysis results at screening, as judged by the investigator.

          7. Any clinically significant abnormal findings in supine vital signs, after 10 minutes
             of supine rest, at screening and/or admission to the unit, defined as: (a) Systolic
             blood pressure < 90 mmHg or ≥ 150 mmHg (b) Diastolic blood pressure < 50 mmHg or ≥ 95
             mmHg and (c) Heart rate < 45 or > 90 beats per minute

          8. Any clinically important abnormalities in rhythm, conduction or morphology of the
             resting 12-lead ECG that, as judged by the investigator, that may interfere with the
             interpretation of QTc interval changes, including abnormal ST-T-wave morphology or
             pronounced left ventricular hypertrophy.

          9. Prolonged QTcF > 460 ms for females and QTcF > 450 ms for males or family history of
             long QT syndrome.

         10. PR (PQ) interval shortening < 110 ms or evidence of ventricular pre-excitation).

         11. PR (PQ) interval prolongation > 240 ms, intermittent second (Wenckebach block while
             asleep is not exclusive) or third degree AV block.

         12. Persistent or intermittent complete bundle branch block with QRS > 120 ms or evidence
             of pronounced ventricular hypertrophy or pre-excitation.

         13. Any positive result on screening for serum hepatitis B surface antigen (HBsAg),
             hepatitis C antibody and human immunodeficiency virus (HIV) antibody.

         14. Known or suspected history of drug abuse, as judged by the investigator.

         15. Current smokers or those who have smoked or used nicotine products within the 3 months
             prior to screening.

         16. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol, as
             judged by the investigator.

         17. Positive screen for drugs of abuse, alcohol or cotinine at screening or on each
             admission to the unit.

         18. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as
             judged by the investigator or history of hypersensitivity to drugs with a similar
             chemical structure or class to AZD9496.

         19. Excessive intake of caffeine/xanthine containing drinks or food (e.g., coffee, tea,
             chocolate), as judged by the investigator.

         20. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks
             prior to the first administration of IMP.

         21. Use of any prescribed or non-prescribed medication including antacids, analgesics
             (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of
             20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to
             the first administration of IMP or longer if the medication has a long half-life Note:
             Hormonal replacement therapy is not allowed for females.

         22. Plasma donation within 1 month of screening or any blood donation/loss more than 500
             mL during the 3 months prior to screening

         23. Has received another new chemical entity (defined as a compound which has not been
             approved for marketing) within 3 months of the first administration of IMP in this
             study. The period of exclusion is 3 months after the final dose from previous study or
             1 month after the last visit of previous study, whichever is the longest. ote:
             Subjects consented and screened, but not dosed in this study or a previous phase I
             study, are not excluded.

         24. Involvement of any AstraZeneca, PAREXEL or study site employee or their close
             relatives

         25. Judgment by the investigator that the subject should not participate in the study if
             they have any ongoing or recent (i.e., during the screening period) minor medical
             complaints that may interfere with the interpretation of study data or are considered
             unlikely to comply with study procedures, restrictions and requirements.

         26. Subjects who are vegans or have medical dietary restrictions.

         27. Subjects who cannot communicate reliably with the investigator.

         28. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship,
             trusteeship, or committed to an institution by governmental or juridical order.