A Phase 1 Study to Assess the Pharmacokinetics of AZD9977 Administered Alone and in Combination With Itraconazole in Healthy Volunteers

This is an open-label, non-randomized, fixed sequence study conducted at a single study
center with primary aim to assess the pharmacokinetics (PK) of AZD9977 in healthy volunteers
when administered alone and in combination with multiple doses of itraconazole. Two types of
treatments (treatment period 1 and treatment period 2) will be administered in a fixed order
separated by a washout period of 3 days or more. Treatment period 1 will be single AZD9977
100 mg (Dose 1) administration, in the fed state, on Day 1 followed by at least 3 days
washout period. For treatment period 2, Itraconazole will be administered daily 200 mg (Dose
2) from Day 4 to Day 8 plus AZD9977 100 mg (Dose 1, fed state) will be administered as a
single dose on Day 7. Dose of itraconazole has to be taken at -1 hour (1 hour prior to
AZD9977 dosing) when co-administered with AZD9977.

Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study specific
procedures.

2. Healthy male and female participants of non-childbearing potential aged 18 - 55 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 one of the following criteria:

1. Postmenopausal defined as amenorrhea for at least 12 months or more following
cessation of all exogenous hormonal treatments and follicle stimulating hormone
(FSH) levels ≥40 mlU/ml.

2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral
oophorectomy or bilateral salpingectomy but not tubal ligation.

4. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50
kg and no more than 100 kg inclusive.

Exclusion Criteria:

1. History of any clinically significant disease or disorder which, in the opinion of the
PI, may either put the volunteer at risk because of participation in the study, or
influence the results or the volunteer's ability to participate in the study..

2. History or presence of gastrointestinal, 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. Any clinically significant abnormalities in clinical chemistry, hematology, or
urinalysis results, as judged by the PI including serum potassium > 5.0 mmol/L, serum
hsTNT > 14ng/mL, and NT pro BNP > 124 pg/ml.

5. Any clinically significant abnormal findings in vital signs as specified below and as
judged by the PI at screening and on admission including:

1. Systolic blood pressure (SBP) < 90 mmHg or > 140 mmHg.

2. Diastolic blood pressure (DBP) < 50 mmHg or > 90 mmHg.

3. HR < 45 or > 90 beats per minute (bpm).

6. Any clinically significant abnormalities on 12-lead ECG, as judged by the PI.

7. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C
antibody, and human immunodeficiency virus (HIV) antibody.

8. Known or suspected history of drug abuse in the last 12 months as judged by the
Investigator.

9. 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 begins 3 months after the final dose or 1 month after
the last visit whichever is the longest.

10. Plasma donation within 1 month of screening or any blood donation/loss more than 500
mL during the 3 months prior to screening.

11. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as
judged by the PI or history of hypersensitivity to drugs with a similar chemical
structure or class to AZD9977.

12. Current smokers or those who have smoked or used nicotine products (including e
cigarettes) within the 3 months prior to screening.

13. Positive screen for drugs of abuse, cotinine or alcohol at screening or on each
admission to the study center.

14. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks
prior to the first administration of IMP.

15. 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.

16. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol in
the last 12 months as judged by the PI.

17. Involvement of any AstraZeneca, PAREXEL or study site employee or their close
relatives.

18. Participants who have previously received AZD9977.

19. Judgment by the PI that the participant 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.

20. Vulnerable participants , e.g., kept in detention, protected adults under
guardianship, trusteeship, or committed to an institution by governmental or juridical
order.

21. Participants with any special dietary restrictions such as participants that are
lactose intolerant or are vegetarians/vegans.

22. Drugs affecting CYP3A4 (itraconazole) should be refrained from use for 3 weeks prior
to study commencement and thereafter until study completion.

23. The following exclusion criterion is driven by contraindications from the proposed
concomitant CYP3A4 (itraconazole) inhibitor medications: Itraconazole (Sporanox)
capsules are contra-indicated in patients with known hypersensitivity to itraconazole
or to any of the excipients.