A75-26 Pharmacokinetics and Safety Following Co-Administration of Nalbuphine Extended-Release With Pirfenidone or Nintedanib: A Phase 1 Drug-Drug Interaction Study

Rationale

Pirfenidone and nintedanib are standard-of-care treatments for idiopathic pulmonary fibrosis (IPF). No drugs are specifically approved to treat the chronic cough that commonly accompanies IPF, and this remains an unmet need. Nalbuphine extended-release (NAL ER) is a kappa opioid receptor agonist and mu opioid receptor antagonist that acts centrally and peripherally on the cough reflex arc and is under investigation for the treatment of chronic cough in patients with IPF. NAL00-105 was a Phase 1 study evaluating steady-state pharmacokinetics (PK) and safety following co-administration of NAL ER and pirfenidone or nintedanib in healthy adults (NCT07015398).

Methods

This was a 2-part, open-label, drug-drug interaction study that enrolled 132 healthy adults aged 18 to 60 years (Figure). Part A evaluated NAL ER 108 mg as the object and pirfenidone 801 mg 3 times daily (TID; Cohort A1) or nintedanib 150 mg twice daily (BID; Cohort A2) as the precipitant. Part B evaluated pirfenidone 801 mg (Cohort B1) or nintedanib 150 mg (Cohort B2) as the object and NAL ER 108 mg BID as the precipitant. The primary objectives were to assess the effect of steady-state pirfenidone or nintedanib on the PK of NAL ER and the effect of steady-state NAL ER on the PK of pirfenidone or nintedanib. The secondary objective was the evaluation of safety and tolerability of the study treatments.

Results

Neither pirfenidone nor nintedanib had a clinically meaningful effect on the PK of NAL ER: Cohort A1 geometric mean ratio (GMR) was 88.4% for Cmax and 96.4% for AUC0-inf, and Cohort A2 GMR was 114.3% for Cmax and 119.4% for AUC0-inf. Similarly, NAL ER did not have a clinically meaningful effect on the PK of either pirfenidone or nintedanib; Cohort B1 GMR was 83.1% for Cmax and 89.3% for AUC0-inf, and Cohort B2 GMR was 79.9% for Cmax and 93.8% for AUC0-inf. Adverse events were Grade 1 or 2, reversible, and consistent with the known safety profiles of the test drugs.

Conclusions

No clinically meaningful PK interactions were observed between NAL ER and pirfenidone or nintedanib.

This abstract is funded by: Trevi Therapeutics