NCT03720366

A Study of Perpetrator Drug Interactions of Enasidenib in AML Patients

A Phase 1, 2-Part, Multicenter, Open-Label, 3-Arm Study to Determine the Effect of Enasidenib (CC-90007) on the Pharmacokinetics of Single Oral Doses of Caffeine, Dextromethorphan, Fexofenadine, Flurbiprofen, Midazolam, Omeprazole, Pioglitazone, and Rosuvastatin in Patients With Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Celgene · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a 2-part, open-label, interventional study conducted in approximately 42 subjects with AML harboring an IDH2 mutation. The overall study is a 3-arm investigation of the PK effects of enasidenib at steady state on the probe compounds. (Part 1), followed by treatment continuation up to 28 months (Part 2). Each arm utilizes different probe compounds; enrolls a separate cohort of approximately 14 subjects; and consists of 2 parts - investigation of the PK effects of enasidenib on the respective probe compound(s) (Part 1), followed by an enasidenib treatment extension (Part 2).

Detailed description

Subjects can only be enrolled in one treatment arm. The probes (which are given twice) used in the study are approved for use in the countries where the study will be conducted. The probes in Arm 1 consist of single doses of caffeine (100mg), dextromethorphan (30 mg), flurbiprofen (50 mg), midazolam (0.03 mg/kg), and omeprazole (40 mg). Arm 2 probes consist of digoxin (0.25 mg), and rosuvastatin (10 mg). Arm 3 probe is pioglitazone (15 mg). Enasidenib is administered orally. All probes, except for midazolam, are administered orally. Midazolam will be administered intravenously. In Part 1 (equivalent to Cycle 1), eligible subjects will receive the probes on Day -1, followed by the first dose of enasidenib on Day 1. Enasidenib will continue to be taken once daily for 28 days. Blood samples for pharmacokinetic analysis will be collected according to a set schedule. Subjects will receive the probes a second time on Day 28. Part 2 of the study begins the next day when the subject begins a second round of daily enasidenib doses (equivalent to Cycle 2). Safety assessment s and procedures consistent with AML standard of care will continue.

Conditions

• Leukemia, Myeloid, Acute

Interventions

Type	Name	Description
DRUG	enasidenib	enasidenib
DRUG	Arm 1 probes	caffeine, dextromethorphan, flurbiprofen, midazolam, and omeprazole
DRUG	Arm 2 Probes	digoxin and rosuvastatin
DRUG	Arm 3 probes	pioglitazone

Timeline

• Start date: 2018-10-04
• Primary completion: 2023-09-22
• Completion: 2023-12-22
• First posted: 2018-10-25
• Last updated: 2024-02-28

Locations

10 sites across 2 countries: Australia, South Korea

Regulatory

• FDA-regulated drug study