Carcinoma, Renal Cell
Conditions
Keywords
Renal Cell Carcinoma, AV-951, tivozanib
Brief summary
This phase 2 trial is evaluating the antineoplastic activity of tivozanib (AV-951) in treating patients with recurrent or metastatic renal cell cancer. Tivozanib (AV-951) is a VEGF-receptor tyrosine kinase inhibitor, and may stop the growth of tumor cells by blocking blood flow to the tumor.
Detailed description
Approximately 200 patients will be enroled into the initial, 16 week, open-label period using 1.5 mg/day dosing. Patients will receive tivozanib (AV-951) continuously for 3 weeks followed by 1 week off study drug. Patients will undergo disease assessment at baseline and after Cycles 2 and 4 and response will be determined by RESIST criteria. After the initial, 16 week open-label period, disease status will be assessed and compared to baseline using modified RECIST criteria: * Patients with greater than or equal to 25% tumor shrinkage will continue on their current dose of tivozanib (AV-951) * Patients with less than 25% tumor change (growth or shrinkage) will be randomly assigned to double-blind tivozanib (AV-951) or matching placebo for 12 weeks * Patients with greater than or equal to 25% tumor growth will be discontinued
Interventions
solid oral dosage form taken daily for three weeks per one month cycle
DRUGPlacebo comparator
solid oral capsule containing excipients dosed daily for three weeks per month
Sponsors
AVEO Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 year old males or females * Patients with recurrent or metastatic renal cell carcinoma (RCC) or primary RCC that is not amendable to surgical intervention * Histologically or cytologically confirmed renal cell carcinoma * Measurable disease * No more than one prior systemic treatment (chemotherapy or immunotherapy) for RCC. * No active brain metastases * Karnofsky performance status ≥ 70%, life expectancy ≥ 3 months * No childbearing potential, or use of effective contraception during the study and for 4 weeks after the last dose of study drug * Archival paraffin embedded tumor tissue, if available. * Ability to give written informed consent
Exclusion criteria
* Pregnant or lactating women * Primary CNS malignancies; active CNS metastases * Hematologic malignancies (includes: leukemia, any form; lymphoma; and multiple myeloma) * Any of the following hematologic abnormalities: * Hemoglobin ≤ 9.0 g/dL * ANC \< 1500 per mm3 * Platelet count \< 100,000 per mm3 * Any of the following serum chemistry abnormalities: * Total bilirubin \> 1.5 × the ULN * AST or ALT ≥ 2.5 × the ULN * Serum albumin \< 3.0 g/dL * Creatinine \> 1.7 × ULN (or calculated CLCR \<50 mL/min/1.73 m2) * Proteinuria \> 2.5 g/24 hours or 4+ with urine dipstick * Significant cardiovascular disease, including: * Active clinically symptomatic left ventricular failure * Active HTN (diastolic blood pressure \> 100 mmHg). Patients with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 4 weeks * Uncontrolled hypertension: Blood pressure \>140/90 mmHg on more than 2 antihypertensive medications. * Myocardial infarction within 3 months prior to administration of first study dose * Unhealed wounds (including active gastric ulcers) * Serious/active infection; infection requiring parenteral antibiotics * Inadequate recovery from prior antineoplastic therapy * Inadequate recovery from any prior surgical procedure; major surgical procedure within 4 weeks prior to study entry * Life-threatening illness or organ system dysfunction compromising safety evaluation * Psychiatric disorder, altered mental status precluding informed consent or necessary testing * Inability to comply with protocol requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | 28 weeks after study entry | To determine the safety and tolerability of tivozanib (AV-951) with the protocol-specified dose schedule |
| Objective Response [Complete Response (CR) + Partial Response (PR)] Rate at 16 Week Open-Label Period (All Treated Population) | 16 weeks after study entry | The ORR is defined as the rate of (CR+PR). Objective response rates following the 16-week, open-label period (investigator assessment and IRR assessment) were estimated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and was assessed by magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Overall Response (OR) = CR + PR. |
| Percentage of Randomly Assigned Subjects Remaining Progression Free at 12 Weeks Following Random Assignment to Tivozanib (AV-951) or Placebo | 28 weeks after study entry | Percentages of subjects remaining progression-free at 12 weeks post-randomization were compared across the 2 treatment arms in the ITT population. A Cochran-Mantel- Haenszel (CMH) test of general association was used, stratifying by country to evaluate the null hypothesis that treatment arm is not associated with subjects remaining progression-free. Non-completers were treated as failures. Progression is defined using RECIST v1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization ) | 28 weeks from study entry | PFS after randomization in the ITT population was described using the Kaplan-Meier methodology. PFS was compared across treatment arms using the log-rank test. |
| Overall Progression-free Survival (From Start of Treatment) | 12 months from study entry | Number of subjects with Overall PFS (from start of treatment) was estimated using the Kaplan-Meier methodology. Subjects randomized to receive placebo were censored at randomization. Withdrawals are also censored. An alternative analysis was conducted in which PFS for subjects randomized to receive tivozanib was weighted more heavily to compensate for the information loss from randomization of other subjects to receive placebo. Additional analyses in which withdrawal was considered a PFS event were also conducted. |
| Time to Peak Plasma Concentration (Tmax) of Tivozanib in a Subset of Subjects | Cycle 1, Day 1: Pre-dose and 2, 4 and 24 hours post dose; Cycle 1, Day 8: Pre-dose; Cycle 1, Day 21: Pre-dose and 2, 4, 24, 48, and 96 hours post dose; Cycle 2 (Day 1): Pre-dose | Tivozanib concentrations in human serum were determined. The PK population included all subjects who had taken at least 1 dose of tivozanib and whose PK profile(s) were evaluable. All subjects received 1.5 mg tivozanib (1.3397 mg free base) in Cycle 1. |
| Maximum Observed Serum Concentration During a Dosing Interval at Steady State (Cmax) | Cycle 1, Day 1: Pre-dose and 2, 4 and 24 hours post dose; Cycle 1, Day 8: Pre-dose; Cycle 1, Day 21: Pre-dose and 2, 4, 24, 48, and 96 hours post dose; Cycle 2 (Day 1): Pre-dose | Tivozanib concentrations in human serum were determined. The PK population included all subjects who had taken at least 1 dose of tivozanib and whose PK profile(s) were evaluable. All subjects received 1.5 mg tivozanib (1.3397 mg free base) in Cycle 1. |
| Area Under the Serum Concentration Versus Time Curve From Zero to the Last Quantifiable Sampling Point [AUC(0→24)] | 28 weeks from study entry | Tivozanib concentrations in human serum were determined. The PK population included all subjects who had taken at least 1 dose of tivozanib and whose PK profile(s) were evaluable. All subjects received 1.5 mg tivozanib (1.3397 mg free base) in Cycle 1. |
Countries
India, Russia, Ukraine
Participant flow
Recruitment details
Participants who met all the inclusion and none of the exclusion criteria were enrolled
Pre-assignment details
All participants underwent inclusion and exclusion criteria assessment and all eligible subjects signed the informed consent before undergoing any study related procedures. All the study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| Open-label Period:Tivozanib (AV-951) Subjects were enrolled into the initial, 16-week, open-label period and received tivozanib at a dose of 1.5 mg/day (oral administration). Subjects received tivozanib continuously for 3 weeks followed by 1 week off study drug (1 cycle = 3 weeks on, 1 week off). After 16 weeks (4 cycles), disease status was assessed and compared to baseline. Tivozanib was to be discontinued following disease progression or unacceptable toxicity. | 272 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Period (12 Weeks) | Discontinued due to other reasons | 0 | 3 | 7 |
| Double-Blind Period (12 Weeks) | Progressive disease | 0 | 23 | 2 |
| Maintenance Period | Discontinued due to other reasons | 68 | 0 | 0 |
| Maintenance Period | Progressive disease | 80 | 0 | 0 |
| Open Label Period (16 Weeks) | Discontinued due to other reasons | 26 | 0 | 0 |
| Open Label Period (16 Weeks) | Progressive disease | 50 | 0 | 0 |
Baseline characteristics
| Characteristic | Open-label Period:Tivozanib (AV-951) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 272 Participants |
| Age, Continuous | 56.3 years STANDARD_DEVIATION 9.5 |
| Body Mass Index | 26.5 kg/m^2 STANDARD_DEVIATION 4.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 271 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 81 Participants |
| Sex: Female, Male Male | 191 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 215 / 272 | 31 / 61 | 32 / 57 |
| serious Total, serious adverse events | 16 / 272 | 2 / 61 | 3 / 57 |
Outcome results
Primary
Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs)
To determine the safety and tolerability of tivozanib (AV-951) with the protocol-specified dose schedule
Time frame: 28 weeks after study entry
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open-label Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Discontinuations due to adverse events | 10 Participants |
| Open-label Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Serious adverse events | 16 Participants |
| Open-label Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Treatment-related adverse events | 174 Participants |
| Open-label Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Adverse events | 215 Participants |
| Open-label Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Grade 3 or higher adverse events | 86 Participants |
| Open-label Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Deaths | 6 Participants |
| Double-blind Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Grade 3 or higher adverse events | 8 Participants |
| Double-blind Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Treatment-related adverse events | 13 Participants |
| Double-blind Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Discontinuations due to adverse events | 1 Participants |
| Double-blind Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Deaths | 1 Participants |
| Double-blind Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Serious adverse events | 2 Participants |
| Double-blind Period: Tivozanib (AV-951) | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Adverse events | 31 Participants |
| Double-blind Period: Placebo | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Discontinuations due to adverse events | 3 Participants |
| Double-blind Period: Placebo | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Deaths | 2 Participants |
| Double-blind Period: Placebo | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Treatment-related adverse events | 7 Participants |
| Double-blind Period: Placebo | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Adverse events | 32 Participants |
| Double-blind Period: Placebo | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Serious adverse events | 3 Participants |
| Double-blind Period: Placebo | Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) | Grade 3 or higher adverse events | 10 Participants |
Primary
Objective Response [Complete Response (CR) + Partial Response (PR)] Rate at 16 Week Open-Label Period (All Treated Population)
The ORR is defined as the rate of (CR+PR). Objective response rates following the 16-week, open-label period (investigator assessment and IRR assessment) were estimated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and was assessed by magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Overall Response (OR) = CR + PR.
Time frame: 16 weeks after study entry
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open-label Period: Tivozanib (AV-951) | Objective Response [Complete Response (CR) + Partial Response (PR)] Rate at 16 Week Open-Label Period (All Treated Population) | Partial response | 66 Participants |
| Open-label Period: Tivozanib (AV-951) | Objective Response [Complete Response (CR) + Partial Response (PR)] Rate at 16 Week Open-Label Period (All Treated Population) | Complete response | 1 Participants |
| Double-blind Period: Tivozanib (AV-951) | Objective Response [Complete Response (CR) + Partial Response (PR)] Rate at 16 Week Open-Label Period (All Treated Population) | Partial response | 49 Participants |
| Double-blind Period: Tivozanib (AV-951) | Objective Response [Complete Response (CR) + Partial Response (PR)] Rate at 16 Week Open-Label Period (All Treated Population) | Complete response | 0 Participants |
95% CI: [19.6, 30.2]
95% CI: [13.6, 23.1]
Primary
Percentage of Randomly Assigned Subjects Remaining Progression Free at 12 Weeks Following Random Assignment to Tivozanib (AV-951) or Placebo
Percentages of subjects remaining progression-free at 12 weeks post-randomization were compared across the 2 treatment arms in the ITT population. A Cochran-Mantel- Haenszel (CMH) test of general association was used, stratifying by country to evaluate the null hypothesis that treatment arm is not associated with subjects remaining progression-free. Non-completers were treated as failures. Progression is defined using RECIST v1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: 28 weeks after study entry
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-label Period: Tivozanib (AV-951) | Percentage of Randomly Assigned Subjects Remaining Progression Free at 12 Weeks Following Random Assignment to Tivozanib (AV-951) or Placebo | 35 Participants |
| Double-blind Period: Tivozanib (AV-951) | Percentage of Randomly Assigned Subjects Remaining Progression Free at 12 Weeks Following Random Assignment to Tivozanib (AV-951) or Placebo | 16 Participants |
| Double-blind Period: Placebo | Percentage of Randomly Assigned Subjects Remaining Progression Free at 12 Weeks Following Random Assignment to Tivozanib (AV-951) or Placebo | 30 Participants |
| Independent Radiology Reviewer (Placebo) | Percentage of Randomly Assigned Subjects Remaining Progression Free at 12 Weeks Following Random Assignment to Tivozanib (AV-951) or Placebo | 12 Participants |
p-value: 0.001Cochran-Mantel-Haenszel
p-value: 0.001Cochran-Mantel-Haenszel
Secondary
Area Under the Serum Concentration Versus Time Curve From Zero to the Last Quantifiable Sampling Point [AUC(0→24)]
Tivozanib concentrations in human serum were determined. The PK population included all subjects who had taken at least 1 dose of tivozanib and whose PK profile(s) were evaluable. All subjects received 1.5 mg tivozanib (1.3397 mg free base) in Cycle 1.
Time frame: 28 weeks from study entry
Population: The PK population had 21 subjects. However, there were subjects with missing data for both Cycle 1 Day 1 and Cycle 1 Day 21. Hence, the number of participants analyzed varies i.e, 20 for Cycle 1 Day 1 and 16 for Cycle 1 Day 21.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-label Period: Tivozanib (AV-951) | Area Under the Serum Concentration Versus Time Curve From Zero to the Last Quantifiable Sampling Point [AUC(0→24)] | Cycle 1 Day 1 | 258.2 h*ng/mL | Standard Deviation 197 |
| Open-label Period: Tivozanib (AV-951) | Area Under the Serum Concentration Versus Time Curve From Zero to the Last Quantifiable Sampling Point [AUC(0→24)] | Cycle 1 Day 21 | 0 h*ng/mL | Standard Deviation 0 |
Secondary
Maximum Observed Serum Concentration During a Dosing Interval at Steady State (Cmax)
Tivozanib concentrations in human serum were determined. The PK population included all subjects who had taken at least 1 dose of tivozanib and whose PK profile(s) were evaluable. All subjects received 1.5 mg tivozanib (1.3397 mg free base) in Cycle 1.
Time frame: Cycle 1, Day 1: Pre-dose and 2, 4 and 24 hours post dose; Cycle 1, Day 8: Pre-dose; Cycle 1, Day 21: Pre-dose and 2, 4, 24, 48, and 96 hours post dose; Cycle 2 (Day 1): Pre-dose
Population: The PK population had 21 subjects. However, there were subjects with missing data for both Cycle 1 Day 1 and Cycle 1 Day 21. Hence, the number of participants analyzed varies i.e, 20 for Cycle 1 Day 1 and 16 for Cycle 1 Day 21.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-label Period: Tivozanib (AV-951) | Maximum Observed Serum Concentration During a Dosing Interval at Steady State (Cmax) | Cycle 1 Day 1 | 15.51 ng/mL | Standard Deviation 11.7 |
| Open-label Period: Tivozanib (AV-951) | Maximum Observed Serum Concentration During a Dosing Interval at Steady State (Cmax) | Cycle 1 Day 21 | 94.29 ng/mL | Standard Deviation 37.8 |
Secondary
Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization )
PFS after randomization in the ITT population was described using the Kaplan-Meier methodology. PFS was compared across treatment arms using the log-rank test.
Time frame: 28 weeks from study entry
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open-label Period: Tivozanib (AV-951) | Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization ) | Number of censored subjects | 38 Participants |
| Open-label Period: Tivozanib (AV-951) | Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization ) | Number of subjects with progression | 23 Participants |
| Double-blind Period: Tivozanib (AV-951) | Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization ) | Number of subjects with progression | 33 Participants |
| Double-blind Period: Tivozanib (AV-951) | Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization ) | Number of censored subjects | 24 Participants |
| Double-blind Period: Placebo | Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization ) | Number of subjects with progression | 22 Participants |
| Double-blind Period: Placebo | Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization ) | Number of censored subjects | 39 Participants |
| Independent Radiology Reviewer (Placebo) | Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization ) | Number of censored subjects | 33 Participants |
| Independent Radiology Reviewer (Placebo) | Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization ) | Number of subjects with progression | 24 Participants |
p-value: 0.005Log Rank
p-value: 0.129Log Rank
Secondary
Overall Progression-free Survival (From Start of Treatment)
Number of subjects with Overall PFS (from start of treatment) was estimated using the Kaplan-Meier methodology. Subjects randomized to receive placebo were censored at randomization. Withdrawals are also censored. An alternative analysis was conducted in which PFS for subjects randomized to receive tivozanib was weighted more heavily to compensate for the information loss from randomization of other subjects to receive placebo. Additional analyses in which withdrawal was considered a PFS event were also conducted.
Time frame: 12 months from study entry
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Open-label Period: Tivozanib (AV-951) | Overall Progression-free Survival (From Start of Treatment) | Number of subjects with progression | 47 Participants |
| Open-label Period: Tivozanib (AV-951) | Overall Progression-free Survival (From Start of Treatment) | Number of censored subjects | 14 Participants |
| Double-blind Period: Tivozanib (AV-951) | Overall Progression-free Survival (From Start of Treatment) | Number of censored subjects | 24 Participants |
| Double-blind Period: Tivozanib (AV-951) | Overall Progression-free Survival (From Start of Treatment) | Number of subjects with progression | 33 Participants |
| Double-blind Period: Placebo | Overall Progression-free Survival (From Start of Treatment) | Number of subjects with progression | 36 Participants |
| Double-blind Period: Placebo | Overall Progression-free Survival (From Start of Treatment) | Number of censored subjects | 25 Participants |
| Independent Radiology Reviewer (Placebo) | Overall Progression-free Survival (From Start of Treatment) | Number of subjects with progression | 24 Participants |
| Independent Radiology Reviewer (Placebo) | Overall Progression-free Survival (From Start of Treatment) | Number of censored subjects | 33 Participants |
p-value: 0.003Log Rank
p-value: 0.089Log Rank
Secondary
Time to Peak Plasma Concentration (Tmax) of Tivozanib in a Subset of Subjects
Tivozanib concentrations in human serum were determined. The PK population included all subjects who had taken at least 1 dose of tivozanib and whose PK profile(s) were evaluable. All subjects received 1.5 mg tivozanib (1.3397 mg free base) in Cycle 1.
Time frame: Cycle 1, Day 1: Pre-dose and 2, 4 and 24 hours post dose; Cycle 1, Day 8: Pre-dose; Cycle 1, Day 21: Pre-dose and 2, 4, 24, 48, and 96 hours post dose; Cycle 2 (Day 1): Pre-dose
Population: The PK population had 21 subjects. However, there were subjects with missing data for both Cycle 1 Day 1 and Cycle 1 Day 21. Hence, the number of participants analyzed varies i.e, 20 for Cycle 1 Day 1 and 16 for Cycle 1 Day 21.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-label Period: Tivozanib (AV-951) | Time to Peak Plasma Concentration (Tmax) of Tivozanib in a Subset of Subjects | Cycle 1 Day 1 | 7.122 hours | Standard Deviation 8.511 |
| Open-label Period: Tivozanib (AV-951) | Time to Peak Plasma Concentration (Tmax) of Tivozanib in a Subset of Subjects | Cycle 1 Day 21 | 3.64 hours | Standard Deviation 5.61 |