A Study to Evaluate the Amount of Drug That Becomes Available in the Blood Circulation When Savolitinib is Administered Alone and in Combination With Itraconazole

Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study specific procedures.
2. Healthy male subjects with suitable veins for cannulation or repeated venipuncture: non-Japanese male subjects aged 18 to 65 years (inclusive).
3. Have a body mass index between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
4. Alanine aminotransferase, aspartate aminotransferase and total bilirubin within normal limits for the institution at screening and Day -1.
5. Have a calculated creatinine clearance greater than 60 mL/min using the Cockcroft-Gault formula at Screening.
6. Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in the protocol.

Exclusion criteria:

1. Healthy subjects of Japanese ethnicity and any healthy subject that has 1 parent or grandparent (maternal or paternal) of Japanese ethnicity.
2. 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.
3. History or presence of GI, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
4. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
5. Planned in-patient surgery, dental procedure or hospitalisation during the study.
6. Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, 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. Abnormal vital signs, after 5 minutes supine rest at screening and Day -1, defined as any of the following:

(1) Systolic BP \<90 mmHg or ≥140 mmHg (2) Diastolic BP \<50 mmHg or ≥90 mmHg (3) Heart rate \<45 or \>85 beats per minute (BPM) 9) Any clinically important abnormalities in rhythm, conduction or morphology of the 12-lead resting ECG that may interfere with the interpretation of QTc interval changes.

These include healthy subjects with any of the following:

1. Abnormal ST-T-wave morphology, particularly in the protocol defined primary lead (V2) or left ventricular hypertrophy.
2. PR interval shortening \<120 ms (PR \>110 ms but \<120 ms is acceptable if there is no evidence of ventricular pre-excitation).
3. PR interval prolongation (\>200 ms). Intermittent second (Type 1 second degree block \[Wenckebach Phenomenon\] while asleep is not exclusive\]) or third degree atrioventricular (AV) block, or AV dissociation.
4. Persistent or intermittent complete bundle branch block (BBB), incomplete BBB, or intraventricular conduction delay with QRS \>110 ms. Subjects with QRS \>110 ms but \<115 ms are acceptable if there is no evidence of eg, ventricular hypertrophy or pre-excitation.
5. Mean resting prolonged QTcF \> 450 ms or shortened QTcF \< 340 ms obtained from 3 ECGs.

10\) A history of additional risk factors for torsades de pointes (TdP) (eg, chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, or family history of unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause TdP).

11\) Known or suspected history of drug abuse, as judged by the PI. 12) Current smokers or those who have smoked or used nicotine products within the previous 30 days.

13\) History of alcohol abuse or excessive intake of alcohol as judged by the PI.

14\) Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate,) as judged by the PI.

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

16\) Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first admission on Study Day -1.

17\) Use of any prescribed or non-prescribed medication including antacids, analgesics (other than use of ibuprofen) up to 72 hours before first dosing day until final follow-up visit, 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 (5 times half-life) if the medication has a long half-life.

18\) Positive screen for drugs of abuse, cotinine (nicotine) and/or alcohol at screening or on each admission to the study centre .

19\) History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to savolitinib or itraconazole.

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

21\) Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days or 5 ½ lives (whichever is longer) of the first administration of IMP in this study.

Note: subjects consented and screened, but not randomized in this study or a previous Phase I study, are not excluded.

22\) Involvement of any AstraZeneca, Parexel, or study centre employee or their close relatives 23) Judgment by the PI that the subject should not participate in the study if they have any ongoing or recent (ie, 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.

24\) Subjects who are vegans, vegetarians or have medical dietary restrictions. 25) Subjects who cannot communicate reliably with the PI. 26) Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

27\) Subjects who have previously received savolitinib.

In addition, any of the following is regarded as a criterion for exclusion from the genetic research:

28\) Previous bone marrow transplant. 29) Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.