NCT04246762

Study in Subjects With Rheumatoid Arthritis to Evaluate the Effect of a Single Dose of Olokizumab on the Pharmacokinetics of Substrates for CYP1A2, CYP2C9, CYP2C19 and CYP3A4

A Phase 1, Open-label, Study in Subjects With Rheumatoid Arthritis to Evaluate the Effect of a Single Dose of Olokizumab on the Pharmacokinetics of Substrates for CYP1A2, CYP2C9, CYP2C19, and CYP3A4

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: R-Pharm International, LLC · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Olokizumab (OKZ) has been shown to reverse the inhibitory effect of IL-6 on the activity of Cytochrome P450 (CYP450) isozymes CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A4/5 in vitro. The goal of the study was to assess the effect of OKZ on the pharmacokinetics (PK) of the CYP450 probe substrates, caffeine (CYP1A2), S-warfarin (CYP2C9), omeprazole (CYP2C19), and midazolam (CYP3A4) in subjects with rheumatoid arthritis (RA).

Detailed description

This was a Phase 1, open-label, 3-period, single-sequence, crossover study in subjects with RA with increased C-reactive protein (CRP). Approximately 15 eligible subjects were planned to be enrolled at approximately 3 study centers to have at least 12 evaluable subjects completing the study. However, if necessary, additional subjects could be dosed to obtain the 12 evaluable subjects required. There was a 35-day Screening Period, followed by a 29-day study duration: eligible patients were administered a cocktail of 4 substrates alone with following 7 days PK-sampling (Period 1); a single subcutaneous dose of 128 mg OKZ was administered (Period 2) approximately 2 weeks prior to the second administration of the cocktail with following 7-days PK-sampling (Period 3). After completion of the Period 3 patients were followed-up for 19 weeks (133 days) for safety evaluations. Overall duration of the study was approximately 200 days (6 and a half months).

Conditions

• Rheumatoid Arthritis

Interventions

Type	Name	Description
DRUG	Olokizumab	Sterile solution for subcutaneous (SC) injection, 128 mg (0.8 mL injection)
DRUG	Omeprazole	Tablets, 20 mg, oral
DRUG	Caffeine	Tablets, 100 mg, oral
DRUG	Warfarin+ Vitamin K	Warfarin -Tablets 10 mg (containing 5 mg S-warfarin), oral. Vitamin K - solution for intravenous injection, 10 mg/mL ampoule, orally.
DRUG	Midazolam	Syrup, 2 mg/mL, oral

Timeline

• Start date: 2021-11-16
• Primary completion: 2022-06-08
• Completion: 2022-10-26
• First posted: 2020-01-29
• Last updated: 2024-08-15
• Results posted: 2024-08-15

Locations

2 sites across 2 countries: Bulgaria, Moldova

Regulatory

• FDA-regulated drug study