A Phase I, Open-label, Randomized, 2-Way Crossover Study to Evaluate the Relative Bioavailability of Intranasal and Oral Varenicline

• Published in: Clinical therapeutics Vol. 43; no. 9; pp. 1595 - 1607
• Main Authors: Nau, Jeffrey, Wyatt, David J., Rollema, Hans, Crean, Christopher S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2021; Elsevier Limited
• Subjects: Administration, Intranasal; Airway management; Bioavailability; Biological Availability; Cigarette smoking; Clinical trials; Cross-Over Studies; Drug addiction; Drug dosages; Dry eye disease; Exocrine glands; Exposure; Eye diseases; FDA approval; Homeostasis; Humans; Inflammation; Metabolism; Nasal Sprays; OC-01 nasal spray; Oral administration; Parameter estimation; Patients; Pharmacokinetics; Phase I study; Substance abuse treatment; Varenicline; Varenicline - adverse effects; United States > US; Maryland; Phase I study; Bioavailability; OC-01 nasal spray; Dry eye disease; Varenicline
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2021.07.020

To estimate the systemic bioavailability of OC-01 (varenicline) nasal spray, an investigational treatment for dry eye disease, relative to oral varenicline approved for smoking cessation. The Study to Evaluate the Relative Bioavailability of Varenicline Administered as OC-01 (Varenicline) Nasal Spray as Compared to Varenicline Administered Orally as Chantix (ZEN study) was a Phase I, open-label, randomized, single-center, 2-way crossover study. On day 1, 22 healthy participants were randomized 1:1 to a single intranasal dose of varenicline 0.12 mg in OC-01 nasal spray or a single oral dose of varenicline 1 mg. On day 15, all participants crossed over to receive a single dose of the alternate treatment. Plasma samples were collected for 6 days after each dose, and pharmacokinetic parameters were estimated using noncompartmental analysis. Tolerability was monitored throughout. After a single dose of intranasal varenicline 0.12 mg in OC-01 nasal spray, peak systemic exposure (mean plasma Cmax) was 0.34 ng/mL, which occurred at a median Tmax of 2.0 hours. In comparison, mean plasma Cmax after oral varenicline 1 mg was 4.63 ng/mL at a median Tmax of 3.0 hours. On the basis of geometric mean ratio point estimates, peak exposure (Cmax) and total exposure (AUC0–∞) after intranasal varenicline 0.12 mg were 7.0% and 7.5%, respectively, of the systemic exposure associated with oral varenicline 1 mg. Dose-normalized Cmax and AUC0–∞ for intranasal varenicline remained 39% and 33% lower versus oral varenicline, respectively. No new or unexpected tolerability signals were detected. At its highest intended single dose in OC-01 nasal spray, intranasal varenicline delivered less drug to the systemic circulation than oral varenicline at its highest approved single dose. ClinicalTrials.gov identifier: NCT04072146.