A PET Study to Determine Biodistribution and Binding Characteristics of [11C]AZ14132516 in Healthy Participants

NCT05818514 | Completed Early Phase 1

• 1 other identifier: D9690C00003
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to measure the regional distribution and binding of \[11C\]AZ14132516 to CCR9 in the abdomen using PET-CT examination in healthy participants. Study details include: The study duration will be up to 60 days. The IV radioligand \[11C\]AZ14132516 will be administered at PET-CT examination: Visit 2 for the pilot panel; Visit 2 and 3 in the main panel. There will be 2 study visits for the pilot panel and 3 study visits for the main panel.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• SUV and SUVR in abdominal regions of interest

  Standardized uptake value (SUV) is the radioactivity concentration in given region of interest normalized for injected radioactivity and body weight. Standardised uptake value ratio (SUVR) is the ratio of SUV in a given region of interest to a reference region without significant radioligand uptake

  Immediately following administration of radioligand

Secondary Outcomes (2)

• Absolute percentage differences of SUV and SUVR, and intraclass correlation coefficients, in regions of interest between two test-retest PET examinations

  10-14 days following initial administration of radioligand

• Number of participants with safety findings, AEs

  Through study completion, up to 49 days (including screening period)

Other Outcomes (1)

• Quantitative estimates of total and specific binding (Kp, VT), including cross-validation of different image analysis approaches

  Immediately following administration of radioligand

Study Arms (1)

[11C]AZ14132516

EXPERIMENTAL

Pilot panel: up to 3 participants to complete 1 PET examination each during the course of the study Main panel: up to 6 participants to complete 2 PET examinations each during the course of the study

Drug: [11C]AZ14132516

Interventions

[11C]AZ14132516 DRUG

Injection of radioligand for PET examinations

Also known as: No other names

[11C]AZ14132516

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
• Able and willing to participate in all scheduled evaluations, abide by all study restrictions, and complete all required tests and procedures.
• Participants ≥ 20 to 65 years of age inclusive, at the time of signing the ICF.
• Participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory parameters and ECG performed before first administration of investigational product.
• Body weight within 50.0 to 100.0 kg and body mass index within the range 18.0 to 30.0 kg/m2 (inclusive).
• Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Female participants:
• In this study:
• WOCBP must have a negative pregnancy test at screening and before PET examination (all premenopausal women, or in case when menstrual status cannot be ascertained in women under the age of 55 years).
• If sexually active with a non-sterilised male partner, must use at least one highly effective method of birth control during the study period and for 7 days following last radioligand administration.
• It is strongly recommended that non-sterilised male partners of female participants of childbearing potential use a male condom plus spermicide during the study period.
• Female participants must not breastfeed and must not donate or retrieve ova for their own use during the study period and for 7 days following last radioligand administration.
• Male participants:
• Non-sterilised male participants who are sexually active with a female partner of childbearing potential must use a condom with spermicide during the study period and for 7 days following last radioligand administration. It is strongly recommended that female partners of male participants also use at least one highly effective method of contraception throughout this period. In addition, male participants must refrain from fathering a child or donating sperm during the study period and for 7 days following last radioligand administration.

You may not qualify if:

• Current significant major or unstable respiratory disease, heart disease, cerebrovascular disease, hematological disease, hepatic disease, renal disease, gastrointestinal disease, or other major diseases.
• Participants with unstable hypertension (as judged by the Investigator) or symptomatic hypotension, history of pre-syncope or syncope due to orthostatic hypotension and/or induced by change of posture (orthostatic hypotension defined as 25 mmHg decrease in systolic and/or 15 mmHg).
• Significant abnormalities on the clinical examination, including neurological and physical examination, vital signs, ECG and clinical.
• Chemistry, hematology, or urine analysis results that may interfere with the study or present a safety risk to the patient.
• Abnormal vital signs, after 10 minutes of supine rest as judged by the PET centre physician. As a guide, any readings outside the following should be considered in the evaluation:
• systolic blood pressure (BP) ≥ 140 mmHg
• diastolic BP ≥ 90 mmHg
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This may include participants with any of the following:
• PR (PQ) interval prolongation of clinical significance as judged by the Investigator
• Intermittent second or third degree AV block (AV block II Mobitz type 1, Wenchebach, while asleep or in deep rest is not disqualifying)
• Incomplete, full, or intermittent bundle branch block (QRS ≤ 110 ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy)
• Abnormal T wave morphology, particularly in the protocol-defined primary lead
• Prolonged QTcF ≥ 470 ms or shortened QTcF ≤ 340 ms or a family history of long QT syndrome.
• Known or suspected systemic infection (eg, hepatitis B virus, hepatitis C virus, HIV and tuberculosis), including previous or ongoing infectious or autoimmune disease.
• Participants must abstain from taking prescription or non-prescription drugs (including vitamins, recreational drugs, and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study intervention until completion of the follow-up visit, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Solna, 171 64, Sweden

Location

Study Officials

• Per Stenkrona

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2023
• First Posted: April 19, 2023
• Study Start: April 27, 2023
• Primary Completion: July 11, 2023
• Study Completion: July 11, 2023
• Last Updated: July 14, 2023

Record last verified: 2023-07

Locations

SE (1)