Clinical trial NCT01454076
Conditions: Nonhematologic Malignancies Lymphoma
Keywords: Cmax: maximum plasma concentration AUC0-tlast: area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
Sponsor: Millennium Pharmaceuticals, Inc.
Start date: 2011-11-10; Completion date: 2016-06-16
Enrollment: 112 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is an open-label, multicenter, sequential, 5-arm, phase 1 study of oral IXAZOMIB designed to assess drug-drug interaction with ketoconazole (Arm 1), the relative bioavailability of 2 capsule formulations of IXAZOMIB (Arm 2), food effect (Arm 3), drug-drug interaction with rifampin (Arm 4), and drug-drug interaction with clarithromycin (Arm 5) in participants with advanced nonhematologic malignancies or lymphoma.

Detailed description:

Arms: arm 1: Ixazomib 2.5 milligram (mg), capsule B, orally, once on Day 1 and 15 along with ketoconazole 400 mg, tablets, orally, once daily from Day 12 to 25 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity. arm 2: Ixazomib 4 mg, capsule A, orally, once on Day 1 followed by ixazomib 4 mg, capsule B once on Day 15 of Cycle 1 (28-day treatment cycle) or ixazomib 4 mg, capsule B, orally, once on Day 1 followed by ixazomib 4 mg, capsule A once on Day 15 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity. arm 3: Ixazomib 4 mg, capsule B, orally, under fasted state, once on Day 1 followed by ixazomib 4 mg, capsule B, orally, under fed state, once on Day 15 of Cycle 1 (28-day treatment cycle) or ixazomib 4 mg, capsule B, orally, under fed state, once on Day 1 followed by ixazomib 4 mg, capsule B, orally, under fasted state, once on Day 15 of Cycle 1 (28-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity. arm 4: Ixazomib, 4 mg, capsule B, orally, once on Day 8 along with rifampin 600 mg, capsule, orally, once daily from Day 1 to 14 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity. arm 5: Ixazomib, 2.5 mg, capsule B, orally, once on Day 6 along with clarithromycin, 500 mg, tablet, orally, twice daily from Day 1 to 16 of Cycle 1 (21-day treatment cycle). After Cycle 1, participants will receive ixazomib 4 mg, capsule B, orally, once daily on Days 1, 8 and 15 of each cycle (28-day treatment cycle) up to a maximum of 12 cycles, until disease progression or unacceptable toxicity.
Interventions: intervention 1: Ixazomib 2.5 mg intervention 2: Ixazomib 4 mg Capsule A intervention 3: Ixazomib 4 mg Capsule B intervention 4: Ketoconazole intervention 5: Rifampin intervention 6: Clarithromycin intervention 7: Ixazomib 4 mg Capsule B
Intervention descriptions: intervention 1: Ixazomib 2.5 mg Capsule B (Cycle 1 only) intervention 2: Ixazomib 4 mg Capsule A (Cycle 1 only) intervention 3: Ixazomib 4 mg Capsule B (Cycle 2 and beyond ) intervention 4: Ketoconazole 400 mg tablets (Cycle 1 only) intervention 5: Rifampin 600 mg capsule (Cycle 1 only) intervention 6: Clarithromycin 500 mg tablets (Cycle 1 only) intervention 7: Ixazomib 4 mg Capsule B (Cycle 1 and beyond)

Protocol documents: