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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
112
Ixazomib 2.5 mg Capsule B (Cycle 1 only)
Ixazomib 4 mg Capsule A (Cycle 1 only)
Ixazomib 4 mg Capsule B (Cycle 2 and beyond )
Unnamed facility
Dallas, Texas, United States
Cmax: Maximum Observed Plasma Concentration for Ixazomib
Time frame: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hours[hrs])post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
Time frame: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Time frame: Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45)
Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities
Time frame: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45
Number of Participants With Clinically Significant Vital Sign Abnormalities
Time frame: Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45
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Ketoconazole 400 mg tablets (Cycle 1 only)
Rifampin 600 mg capsule (Cycle 1 only)
Clarithromycin 500 mg tablets (Cycle 1 only)
Ixazomib 4 mg Capsule B (Cycle 1 and beyond)
Percentage of Participants With Best Overall Response
Best overall response for a participant is best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1: Complete response (CR) was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (\<) 10 millimeter \[mm\]). No new lesions. Partial response (PR) was defined as greater than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease (SD) was defined as not qualifying for CR, PR, Progressive Disease (PD). An increase of \>=20% from the nadir (or baseline, if it represents the point at which the sum of target disease was lowest) represents PD.
Time frame: Baseline up to end of treatment (approximately 1.9 years)