Renal Impairment Does Not Affect Pharmacokinetics, Safety or Tolerability of Zenagamtide

Zenagamtide is a novel, unimolecular glucagon-like peptide-1 and amylin receptor agonist in development for weight management and Type 2 diabetes. This study investigated the pharmacokinetic (PK) properties, safety and tolerability of zenagamtide in participants with various degrees of renal impairment versus participants with normal renal function.

Adults with body mass index 20.0-39.9 kg/m² were categorised based on baseline renal status using the CKD-EPI Collaboration creatinine equation (2021); normal function, mild impairment, moderate impairment, severe impairment and end-stage renal disease (ESRD). Participants received a single subcutaneous dose of zenagamtide 0.3 mg, followed by a 4-week follow-up period. The primary endpoint was area under the zenagamtide plasma concentration-time curve from time zero to infinity (AUC_0-∞). Additional endpoints included maximum observed plasma zenagamtide concentration (C _max) and number of treatment-emergent adverse events (TEAEs).

In total, 42 participants were included (n = 14, normal renal function group; n = 7 per renal impairment group). The range (geometric mean) of zenagamtide AUC_0-∞ and C _max across renal impairment groups were 520-715 h × nmol/L and 2.8-3.5 nmol versus 543 h × nmol/L and 3.2 nmol/L for the normal renal function group, respectively. Overall, TEAEs were reported in 30 (71.4%) participants. TEAEs were non-serious, none were severe and the majority were mild and most frequently gastrointestinal in nature.

Renal impairment did not appear to have a clinically relevant impact on the PK or safety profile of zenagamtide, suggesting that dose adjustment of zenagamtide is not warranted in this population.

ClinicalTrials.gov: NCT06559527.