TSPO Occupancy in the Human Lung

NCT07362290 | Enrolling By Invitation

• 1 other identifier: 24/YH/0091
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators would like to explore the role of TSPO in PAH using a pharmacological challenge agent (XBD173) to modulate TSPO function. In order to appropriately design experimental medicine studies examining TSPO function, the investigators first need an understanding of the relationship between XBD173 dose and occupancy of lung TSPO. The aim of the proposed study, therefore, is to answer three questions:

1. 1.What plasma concentrations of XBD173 are required to cause high occupancy of lung TSPO?
2. 2.What doses of XBD173 are required to achieve these plasma concentrations at steady state?
3. 3.Does taking XBD173 with food affect the plasma concentrations achieved?

Conditions

Healthy Volunteers - Male and Female

Outcome Measures

Primary Outcomes (1)

• To establish the relationship between plasma concentration of XBD173 and TSPO occupancy in the human lung

  This will be achieved by measuring the \[11C\]PBR28 signal in the lungs of healthy individuals in the presence and absence of XBD173. We will use Occupancy % to measure this outcome. \[11C\]PBR28 signal in the lungs will be measured by volume of distribution.

  Up to 4 months

Secondary Outcomes (1)

• To establish the relationship between dose of XBD173 and plasma concentration of XBD173 at steady state , fed state and fasted state.

  Up to 1 week

Study Arms (2)

The TSPO signal in the lungs of healthy individuals, in the presence and absence of XBD173

OTHER

In part A, the investigators will use positron emission tomography (PET) imaging with the TSPO targeting PET ligand \[11C\]PBR28 to quantify the amount of TSPO in the lung. The investigators will then administer XBD173 orally (between 10mg and 90mg), and perform two subsequent \[11C\]PBR28 PET scans spread between two and 24 hours post dosing. XBD173 and \[11C\]PBR28 both bind the same site on the TSPO, and therefore compete with each other for TSPO binding. This allows for quantification of TSPO occupancy by XBD173. Measuring XBD173 plasma concentrations during the PET scan will allow us to learn how much XBD173 is required in the plasma to produce a certain degree of TSPO occupancy in the lung. Using a wide range of doses (10mg-90mg) and scan times (2-24 hours) ensures that some participants will have high TSPO occupancy and some will have low TSPO occupancy. This will allow us to better understand the plasma concentration/occupancy relationship.

Drug: XBD173

Plasma concentrations of XBD173 following oral dosing (in fasting and fed states)

OTHER

Part B will look at what doses of XBD173 are required to achieve the plasma concentration leading to high TSPO occupancy at steady state (to be determined in Part A), and whether taking XBD173 with food affects the plasma concentrations achieved. The investigatorsassume that the plasma concentrations required to cause high TSPO occupancy (identified in Part A) will be achieved with a dose of approximately 60mg. Therefore, in Part B for study visits 1, 2 and 3, participants will receive 6 doses of 60mg XBD173 spread over 3 days and the effect of food investigated by dosing with and without food.

Drug: XBD173

Interventions

XBD173 DRUG

Small molecule experimental medication binding to mitochondrial protein TSPO

Plasma concentrations of XBD173 following oral dosing (in fasting and fed states); The TSPO signal in the lungs of healthy individuals, in the presence and absence of XBD173

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects aged between 25-75 years old
• Able to provide written informed consent prior to any study mandated procedures
• Able to lie comfortably on back for up to 90 minutes at a time (Part A only)
• Female participants of childbearing potential are eligible to participate after a negative highly sensitive pregnancy test if they are taking a highly effective method of contraception during participation in the study and until the end of relevant systemic exposure. The following methods are permitted:
• progesterone implant
• intrauterine device (also called IUD)
• intrauterine hormone-releasing system (also known as IUS)
• bilateral tubal occlusion
• vasectomised partner
• sexual abstinence
• Male participants who are fertile are eligible to participate if they are willing to comply with the contraceptive requirements as listed above \*Definition of fertile females (women of childbearing potential) and of fertile men: For the purpose of this document, a woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. For the purpose of this document, a man is considered fertile after puberty unless their medical notes document that they are permanently sterile.

You may not qualify if:

• Unable to provide informed consent and/or are non-fluent speakers of the English language
• Hypersensitivity to XBD173 or to any of the excipients
• Clinically-significant renal disease (confirmed by creatinine clearance \<30 ml/min per 1.73m2)
• Clinically-significant liver disease (confirmed by serum transaminases \>3 times than upper normal limit)
• History of uncontrolled systemic hypertension
• Acute infection (including eye, dental, and skin infections)
• History of chronic inflammatory disease including HIV, and Hepatitis B
• Women who are pregnant or breastfeeding
• Patients who have received an Investigational Medicinal Product (IMP) within 5 half-lives of the last dose of the IMP or 1 month (which ever is greater) before the baseline visit
• Diagnosis of any condition which may directly or indirectly lead to lung pathology in the opinion of the investigator
• Severe and moderate P450 CY3A4 inhibitors
• o Boceprevir, Clarithromycin, Cobicistat, Idelalisib, Itraconazole, Ketoconazole, Nelfinavir, Ritonavir, Saquinavir, Telaprevir, Telithromycin, Voriconazoleb, Aprepitant, Conivaptan, Crizotinib, Diltiazem, Dronedarone, Erythromycin, Fluconazole, Imatinib, Isavuconazole, Nefazodone, Netupitant, Nilotinib, Posaconazolee, Tofisopam, Verapamil, Delavirdine.
• Severe and moderate P450 CY3A4 inducers
• o Carbamazepine, Enzalutamide, Fosphenytoin, Mitotane, Phenytoin, Rifampicin, Bosentan, Efavirenz, St John's wort, Barbiturates, Nevirapine, Primidone, Rifabutin, Rifapentine.
• TT/AT Genotype at the rs6971 locus

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

NIHR Imperial CRF

London, W12 0HS, United Kingdom

Location

MeSH Terms

Interventions

N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part A will look at the TSPO signal in the lungs of participants, in the presence and absence of a drug to block the specific binding of the PET signal (XBD173). Part B will look at plasma concentrations of XBD173 following oral dosing (in fasting and fed states). This is a single group assignment where participants can take part in both Part A and Part B, or Part A alone, or Part B alone. Parts A and B will run concurrently

Study Record Dates

• First Submitted: September 30, 2025
• First Posted: January 23, 2026
• Study Start: September 19, 2025
• Primary Completion: March 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)