NCT05657613

Drug-Drug Interaction Study of Pacritinib and CYP450,Transporter Substrates, and CYP450 3A4 in Healthy Male Subjects

Drug-Drug Interaction Study of Multiple Doses of Pacritinib and CYP450 And, Transporter Substrates, and CYP450 3A4 Inducers and Inhibitors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: CTI BioPharma · Industry
• Sex: Male
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This is a Phase 1, open-label, fixed-sequence, 2-part DDI study. Subjects will participate in only 1 study part.

Detailed description

This is a Phase 1, open-label, fixed-sequence, 2-part DDI study. Part 1 will evaluate the effect of 14 days of pacritinib 200 mg BID at steady state on the systemic exposure of a cocktail of single doses of cytochrome P450 (caffeine, midazolam, omeprazole) and transporter substrates (digoxin, rosuvastatin, metformin) in 18 healthy male subjects who will participate in 2 treatment periods sequentially separated by a washout period. Part 2 will evaluate the effect of a CYP450 3A4 inducer (bosentan BID) for 7 days and the effect of a CYP450 3A4 inhibitor (fluconazole QD) for 7 days, on the PK of multiple doses of pacritinib 200 mg BID in 36 healthy male subjects. Safety and tolerability will be assessed by AEs, clinical laboratory tests, vital signs, ECGs, and physical examinations.

Conditions

• Drug Interactions

Interventions

Type	Name	Description
DRUG	CYP450 Cocktail and Transporter Substrates with Pacritinib	Day 1: Single oral dose of a cocktail of cytochrome P450 substrates (caffeine 100 mg, midazolam 2 mg, omeprazole 20 mg and metformin (transporter) Day 3: Single oral dose of transporter substrates (digoxin 0.25 mg, rosuvastatin 5 mg) Days 8-22: Oral doses of pacritinib 200 mg BID approximately 12 hours apart Day 17: Single oral dose of transporter substrates (digoxin 0.25 mg and rosuvastatin 5 mg) will be coadministered with the AM dose of pacritinib 200 mg. Day 21: Single oral dose of a cocktail of cytochrome P450 substrates (caffeine 100 mg, midazolam 2 mg, and omeprazole 20 mg) along with transporter substrate (metformin 500 mg) will be coadministered with the AM dose of pacritinib 200 mg.
DRUG	Part 2 -Group A Bosentan 125 mg (CYP450 3A4 inducer) with Pacritinib	Days 1-7: Oral doses of pacritinib 200 mg BID Days 8-14: Oral doses of pacritinib 200 mg BID, coadministered with an oral dose of bosentan 125 mg BID
DRUG	Part 2 Group B - Fluconazole (CYP450 3A4 inhibitor) with Pacritinib	Days 1-7: Oral doses of pacritinib 200 mg BID Days 8-14: Oral doses of pacritinib 200 mg BID, coadministered with an oral dose of fluconazole 200 mg QD.

Timeline

• Start date: 2023-01-03
• Primary completion: 2023-06-08
• Completion: 2023-06-08
• First posted: 2022-12-20
• Last updated: 2024-10-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study