P-1117. An Open-label Phase 1 Study in Healthy Adult Male Participants to Investigate the Absorption, Metabolism, and Excretion of [14C]-Rifaquizinone Following a Single Intravenous Administration
Authors: Al-Ibrahim Mohamed , Keck Bradly , Croft Marie , English Stephen , Barton Eleanor , Kasprenski Loewe , Wang Huan , Ai Changlin , Geng Guozhu , Chen Jing , Ma Zhenkun 
Published: January 2025

Background

Rifaquizinone (RFQ, TNP-2092) is a novel multitargeting drug conjugate in development for the treatment of serious or life-threatening bacterial infections including those caused by gram-positive pathogens that have developed or acquired resistance to commonly used antibiotics and those associated with medical devices. RFQ exerts its antibacterial activity by inhibiting RNA polymerase, DNA gyrase, and topoisomerase IV. This study evaluated the absorption, metabolism, and excretion of RFQ following an intravenous (IV) administration in healthy participants.

Methods

This was an open-label phase 1 study (NCT05074134) conducted at a single site in the USA. Eligible adult male participants were administered a single dose of 300 mg/3 µCi [14C]-RFQ following a standardized meal. Blood, urine, and feces were collected up to 336 hours after initiating IV dosing for pharmacokinetic (PK), radiolabel recovery and metabolite assessments.

Results

A total of 7 participants were enrolled and five participants completed the study. Six participants were included in the PK analysis. The majority (96.9%) of the administered radioactivity was excreted within 120 hours of IV dosing. A mean cumulative mass balance recovery of 102% was achieved after 336 hours post-dose with 98.7% and 2.74% recovered in the feces and urine, respectively. The PK profiles of radioactivity in whole blood and plasma, and RFQ in plasma are summarized in Table 1. The ratio of mean AUC of radioactivity between whole blood and plasma was 0.568. RFQ was identified as the major radioactive component in pooled plasma and pooled feces, accounting for 56.1% and 61.7% of total radioactivity, respectively. The C-25 O-deacetylated RFQ was identified as the major metabolite, accounting for 11.6% of the total radioactivity in pooled feces. No single radioactive component present in urine accounted for greater than 10% of the administered dose.

Conclusion

After a single IV dose of 300 mg/3 µCi [14C]-RFQ, 96.9% of the administered radioactivity was recovered within 120 hours. The majority (98.7%) radioactivity was excreted in the feces. RFQ was the major radioactive component in pooled plasma and feces.

Disclosures

Mohamed Al-Ibrahim, MB ChB, TenNor Therapeutics (Suzhou) Ltd: Investigator Bradly Keck, PhD, TenNor Therapeutics (Suzhou) Ltd: Investigator Marie Croft, PhD, TenNor Therapeutics (Suzhou) Ltd: Investigator Stephen English, BS, TenNor Therapeutics (Suzhou) Ltd: Investigator Eleanor Barton, Master, TenNor Therapeutics (Suzhou) Ltd: Investigator Loewe Kasprenski, MBA, TenNor Therapeutics (Suzhou) Ltd: Investigator Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Changlin Ai, Master of Medicine, TenNor Therapeutics (Suzhou) Ltd: Employee Guozhu Geng, MD, TenNor Therapeutics (Suzhou) Ltd: Employee Jing Chen, Master of Science, TenNor Therapeutics (Suzhou) Ltd: Employee Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee