A Positron-emission Tomography Study to Determine Brain Exposure of [11C]Savolitinib in Healthy Volunteers

NCT06348355 | Completed Phase 1

• 2 other identifiers: D5084C000162023-508334-34-00
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to measure brain exposure of \[11C\]savolitinib in healthy volunteers. This study will determine brain exposure of \[11C\]savolitinib in up to 8 healthy volunteers under physiological conditions, ie, when the BBB is intact. The study design allows up to 3 site visits. Two PET examinations will be performed for each healthy volunteer. The first PET examination will use IV administration of \[11C\]savolitinib. The second PET examination using \[11C\]savolitinib will occur after a single oral dose of 300 mg of savolitinib. PET image analysis will include kinetic compartment modelling using arterial input function, and will generate a set of brain exposure parameters (eg, maximum %ID, maximum \[11C\]savolitinib concentration in brain, partition coefficients between brain and plasma).

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Percentage of injected radioactivity entering the brain (%ID) as %IDmax_brain

  Determine brain exposure of \[11C\]savolitinib following single, IV administration of a microdose in healthy adult volunteers

  0-90 minutes post IV dose of [11C]savolitinib

Secondary Outcomes (14)

• The following endpoint: Cmax_brain SUV

  0-90 minutes post IV dose of [11C]savolitinib

• The following endpoint: Tmax brain

  0-90 minutes post IV dose of [11C]savolitinib

• The following endpoint: AUCbrain 0-90

  0-90 minutes post IV dose of [11C]savolitinib

• The following endpoint: AUCplasma 0-90

  0-90 minutes post IV dose of [11C]savolitinib

• The following endpoint: Kp

  0-90 minutes post IV dose of [11C]savolitinib

Other Outcomes (1)

• Number of participants with safety findings, AEs

  Through study completion, up to 69 days (including screening period)

Study Arms (1)

Healthy Volunteers

EXPERIMENTAL

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.

Drug: [11C]savolitinib; Drug: Savolitinib

Interventions

[11C]savolitinib DRUG

Radiopharmaceutical; IMP; Sterile solution for IV injection, not more than 10 μg, single administration

Healthy Volunteers

Savolitinib DRUG

IMP; 300 mg tablet, oral single administration

Healthy Volunteers

Eligibility Criteria

• Age: 50 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Body weight within 50.0 - 100.0 kg and body mass index within the range 18.0 - 30.0 kg/m2 (inclusive).
• 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.

You may not qualify if:

• 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.
• Current evidence of SARS-CoV-2 infection with some exceptions applied on a case by case basis.
• Positive urine screen for drugs of abuse at screening visit, or known history of drug or alcohol abuse within the past year.
• 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.
• Any clinically significant abnormalities on 12-lead ECG, as judged by the investigator.
• Central nervous system infarction, infection or focal lesions of clinical significance on MRI scans.
• Brain MRI abnormalities that would interfere with image analysis, as determined by the PI
• 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.
• Current significant major or unstable respiratory, heart, cerebrovascular, haematological, hepatic, renal, gastrointestinal diseases, or other major disease.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Solna, 171 64, Sweden

Location

Related Links

• CSR Synopsis

MeSH Terms

Interventions

1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine

Study Officials

• Jonas Svensson, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2024
• First Posted: April 4, 2024
• Study Start: April 12, 2024
• Primary Completion: June 24, 2024
• Study Completion: June 24, 2024
• Last Updated: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

SE (1)