A positron-emission tomography study to determine brain exposure of [11C]savolitinib in healthy volunteers

Study identifier:D5084C00016

ClinicalTrials.gov identifier:NCT06348355

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

A Phase I, Open-label, Positron-Emission Tomography Study to Determine Brain Exposure of [11C]savolitinib in Healthy Volunteers

Medical condition

Healthy Volunteers

Phase

Phase 1

Healthy volunteers

Yes

Study drug

[11C]savolitinib, Savolitinib

Sex

All

Estimated Enrollment

Study type

Interventional

Age

50 Years - 65 Years

Date

Study Start Date: 12 Apr 2024

Estimated Primary Completion Date: 28 Jun 2024

Estimated Study Completion Date: 28 Jun 2024

Study design

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

Verification:

Verified 01 May 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Healthy volunteers must be ≥ 50 to 65 years of age inclusive, at the time of signing the informed consent form and capable of giving informed consent.
2. Body weight within 50.0 – 100.0 kg and body mass index within the range 18.0 – 30.0 kg/m2 (inclusive).
3. Male or female with contraceptive use.
a. Male volunteers:
(i) does not wish to father any children in the 6 months after the study follow-up visit and must use condoms and spermicide with sexual partners who are pregnant or who could become pregnant from the time of dosing until 6 months after savolitinib administration.
b. Female volunteers: Only females not of childbearing potential will be considered for enrollment in the study.

Exclusion Criteria

1. Having known or suspected systemic infection (eg, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, tuberculosis), including previous or on-going infectious or autoimmune disease.
2. Current evidence of SARS-CoV-2 infection with some exceptions applied on a case by case basis.
3. Positive urine screen for drugs of abuse at screening visit, or known history of drug or alcohol abuse within the past year.
4. Any factors that may increase the risk of QTcF prolongation such as congenital of familiar long QT syndrome, chronic hypokalemia not correctable with supplements etc.
5. Any clinically significant abnormalities on 12-lead ECG, as judged by the investigator.
6. Central nervous system infarction, infection or focal lesions of clinical significance on MRI scans.
7. Brain MRI abnormalities that would interfere with image analysis, as determined by the PI
8. Presence of significant abnormalities in the medical history or physical examination or laboratory tests at screening that may interfere with the study or present a safety risk.
9. Current significant major or unstable respiratory, heart, cerebrovascular, haematological, hepatic, renal, gastrointestinal diseases, or other major disease.
10. Any concomitant medications known to be associated with Torsades de Pointes, potent inducers of cytochrome P450 3A4 (CYP3A4), strong inhibitor of CYP1A2, inhibitors or inducers of P-gp.
11. Participation in a research PET or PET/CT study in the previous 12 months, and as per the judgement of the PI participation in this study will not expose the volunteer to radiation in excess of internationally accepted limit.
12. History of autoimmune disease, severe/ongoing allergy or atopy, or history of hypersensitivity to drugs with a similar chemical structure or class to [11C]savolitinib/savolitinib or the excipients of [11C]savolitinib/savolitinib.

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Arms	Assigned Interventions
Experimental: Healthy Volunteers Healthy volunteers will undergo two PET examinations and will receive 2 single IV doses of [11C]savolitinib (total ≤ 20 µg) and radioactivity of 400 ± 10% mBq/70 kg/per PET-CT examination, with total radiation exposure during the study of 3.86 mSv. Healthy volunteers will receive a single 300 mg dose of oral savolitinib approximately 2 hours after the end of the first PET examination and approximately 2 hours before the second IV dose of [11C]savolitinib. The second PET examination can be performed on a separate day, within 14 days after the first PET examination. Oral savolitinib will be given on the same day as the second PET examination.	-

Arms

Assigned Interventions

Experimental: Healthy Volunteers
Healthy volunteers will undergo two PET examinations and will receive 2 single IV doses of [11C]savolitinib (total ≤ 20 µg) and radioactivity of 400 ± 10% mBq/70 kg/per PET-CT examination, with total radiation exposure during the study of 3.86 mSv. Healthy volunteers will receive a single 300 mg dose of oral savolitinib approximately 2 hours after the end of the first PET examination and approximately 2 hours before the second IV dose of [11C]savolitinib. The second PET examination can be performed on a separate day, within 14 days after the first PET examination. Oral savolitinib will be given on the same day as the second PET examination.

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Jonas Svensson

Karolinska Institutet