Phase 1 Trial of Oral Ixabepilone

The MTD was defined as the maximum dose which could be given to 6 participants such that not more than 1 participant experienced a DLT (or fewer than one-third if there were more than 6 treated participants) with at least 2 participants experiencing a DLT at the next higher dose level. The R2PD was to be based on the MTD and the assessment of any relevant chronic toxicities.

Time frame: At the end of Cycle 1 (21 days).

Population: Due to early study discontinuation, the MTD and RP2D of oral ixabepilone at the scheduled doses used in this study were not determined

DLT: any of the following, considered related to ixabepilone, occurring in Cycle 1: Absolute neutrophil count (ANC) \<500 cells/mm\^3 for ≥5 consecutive days or febrile neutropenia of any duration; Grade(Gr)4 thrombocytopenia \<25,000 cells/mm\^3 or Gr3 with bleeding requiring platelet transfusion; Gr3/4 nausea, vomiting, or diarrhea despite use of adequate intervention, fatigue, any other clinically significant drug-related ≥Gr 3 non-hematologic toxicity, delayed recovery (to Gr ≤1 or baseline, except alopecia) from toxicity which delays initiation of Cycle 2 by ≥3 weeks.

Time frame: During Cycle 1 (Day 0 through Day 21)

Population: All participants who received at least one dose of ixabepilone.

Tumor assessment was performed according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR) = disappearance of all clinical and radiological evidence of target lesions; Partial Response (PR) = at least 30% reduction in the sum of the longest diameter of all target lesions; Progressive disease (PD) = at least 20% increase in the sum of the longest diameter of all target lesions; Stable Disease (SD) = neither PR nor PD criteria were met.

Time frame: Tumor assessments performed on Day 1 of every other cycle of therapy, until disease progression or toxicity

Population: All treated participants who received at least one dose of ixabepilone were evaluable for tumor response.

QTc interval was defined as the measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, corrected for heart rate

Time frame: Baseline (Day -1) and Day 1

Population: Since study NCT00632424 (CA163-149) was discontinued early due to variability in oral ixabepilone concentrations with the potential to negatively impact both safety and efficacy, QTc data were collected but not analyzed.

AEs graded according to Common Terminology Criteria Version 3.0 (CTC v 3.0). AE=any new untoward medical occurrence or worsening of a pre-existing medical condition not necessarily having a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, or is an important medical event.

Time frame: From first study drug administration through 30 days post dose

Population: All participants who received at least one dose of ixabepilone.

Laboratory results were graded according to CTC v 3.0. Hematology laboratory evaluations included absolute neutrophil count (ANC), white blood cell count (WBC), platelets (PLT), and hemoglobin (HGB).

Time frame: From first study drug administration through 30 days post dose

Population: All participants who received at least one dose of ixabepilone.

Laboratory results were graded according to CTC v 3.0. Clinical laboratory evaluations included liver function (alanine aminotransferase \[ALT\], Aspartate aminotransferase \[AST\], alkaline phosphatase, and total bilirubin), and renal function (creatinine).

Time frame: From first study drug administration through 30 days post dose

Population: Since study NCT00632424 (CA163-149) was discontinued early due to variability in oral ixabepilone concentrations with the potential to negatively impact both safety and efficacy, liver and renal laboratory data were collected but not summarized.

AEs graded according to Common Terminology Criteria Version 3.0 (CTC v 3.0). AE=any new untoward medical occurrence or worsening of a pre-existing medical condition not necessarily having a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, or is an important medical event.

Time frame: From first study drug administration through 30 days post dose

Population: All participants who received at least one dose of ixabepilone.

Pharmacokinetics (PK) of ixabepilone were derived from plasma concentration versus time data. Individual patient PK parameter values were derived by standard non-compartmental methods by a validated pharmacokinetic analysis program. PK parameters include Cmax (maximum plasma concentration), Cmin (minimum plasma concentration), Tmax (time of maximum plasma concentration), AUC (0-TAU) (area under the curve in one dosing interval), T-half (plasma half-life).

Time frame: Time 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 12.5, 13, 14, 15, 16, 17, 18, 20, 48, 72, and 168 hours post dose

Population: Number of Participants Analyzed =All participants who received any treatment with ixabepilone and had adequate concentration profiles, n=all participants who received ixabepilone and had adequate concentration profiles at the specified time point. Cmax, Cmin, Tmax, AUC (0-TAU), and T-half were not calculated.