Advanced Solid Tumors
Conditions
Brief summary
The purpose of the study was to characterize the safety of investigational agent AG-013736, in patients with solid tumors in this First In Human trial.
Interventions
DRUGAG-013736
Axitinib continuous oral dosing (10 mg once a day, 10 mg twice a day, 20 mg twice a day or 30 mg twice day) in the fed state
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with cytologically or histologically confirmed solid tumor(s) and with at least one measurable disease site * Patients with adequate bone marrow, liver and kidney function * Patients with life expectancy of at least 12 weeks
Exclusion criteria
* Patients who have received chemotherapy, immunotherapy, radiotherapy or any investigational agent within 4 weeks of study entry * Patients with have had a major surgical procedure within 4 weeks of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | Baseline up to Day 28 | MTD is defined as the dose level at which no more than 1 of 6 participants experience dose-limiting toxicity (DLT) following de-escalation from the maximum administered dose (MAD). DLT includes grade (Gr) 2 or greater gastrointestinal toxicities, Gr 3 anemia, nonhematological toxicities (excluding nausea, vomiting, and diarrhea) or Gr 4 neutropenia, thrombocytopenia and inability to resume axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours (hrs) post-dose on Day (D) 1 and 15 of Cycle (C) 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3) | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3) | — |
| Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3) | AUC (0-12)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-12). |
| Apparent Oral Clearance (CL/F) | Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Plasma Decay Half-Life (t1/2) in Fed State Versus Overnight Fasting | Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Maximum Observed Plasma Concentration (Cmax) in Fed State Versus Overnight Fasting | Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2) | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) in Fed State Versus Overnight Fasting | Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2) | — |
| Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] in Fed State Versus Overnight Fasting | Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2) | AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24). |
| Apparent Oral Clearance (CL/F) in Fed State Versus Overnight Fasting | Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Plasma Decay Half-Life (t1/2) | Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Axitinib (10 mg QD + 10 mg/20mg/30mg BID), Fed Single dose of axitinib (AG-013736) 10 mg tablet orally QD followed by 30 mg single dose after 48 hours. Axitinib (AG-013736) 10 mg/ 20 mg/ 30 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles. | 6 |
| Cohort 2: Axitinib 20 mg BID, Fed Axitinib (AG-013736) 20 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles. | 4 |
| Cohort 3: Axitinib 5 mg BID, Fed Axitinib (AG-013736) 5 mg tablet orally BID in fed state continuously in cycles of 4 weeks, up to 8 cycles. | 6 |
| Cohort 4: Axitinib 15 mg QD, Fed Axitinib (AG-013736) 15 mg tablet orally QD in fed state continuously in cycles of 4 weeks, up to 8 cycles. | 6 |
| Cohort 5: Axitinib 5 mg BID, Fasted Axitinib (AG-013736) 5 mg tablet orally BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles. | 8 |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted Axitinib (AG-013736) 2 mg tablet orally BID on the first day of dosing followed by 5 mg BID in fasted state continuously in cycles of 4 weeks, up to 8 cycles. | 6 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 0 | 2 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Moved to rollover protocol | 1 | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Other | 0 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive disease | 3 | 0 | 5 | 3 | 7 | 2 |
Baseline characteristics
| Characteristic | Cohort 1: Axitinib (10 mg QD + 10 mg/20mg/30mg BID), Fed | Cohort 2: Axitinib 20 mg BID, Fed | Cohort 3: Axitinib 5 mg BID, Fed | Cohort 4: Axitinib 15 mg QD, Fed | Cohort 5: Axitinib 5 mg BID, Fasted | Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Total |
|---|---|---|---|---|---|---|---|
| Age Continuous | 53.83 Years STANDARD_DEVIATION 8.75 | 58.50 Years STANDARD_DEVIATION 4.8 | 55.00 Years STANDARD_DEVIATION 7.27 | 56.00 Years STANDARD_DEVIATION 9.44 | 54.88 Years STANDARD_DEVIATION 7.95 | 64.17 Years STANDARD_DEVIATION 10.01 | 56.86 Years STANDARD_DEVIATION 8.53 |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 2 Participants | 2 Participants | 5 Participants | 3 Participants | 20 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 36 |
| serious Total, serious adverse events | 12 / 36 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
MTD is defined as the dose level at which no more than 1 of 6 participants experience dose-limiting toxicity (DLT) following de-escalation from the maximum administered dose (MAD). DLT includes grade (Gr) 2 or greater gastrointestinal toxicities, Gr 3 anemia, nonhematological toxicities (excluding nausea, vomiting, and diarrhea) or Gr 4 neutropenia, thrombocytopenia and inability to resume axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.
Time frame: Baseline up to Day 28
Population: Analysis population included all enrolled participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Treated Participants | Maximum Tolerated Dose (MTD) | 5 mg BID |
Secondary
Apparent Oral Clearance (CL/F)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Population: Analysis population included all enrolled participants who received at least one dose of the study drug. 'n' signifies those participants evaluated for this measure at specific time point for each cohort respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| All Treated Participants | Apparent Oral Clearance (CL/F) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 18.82 Liter/hr (L/hr) |
| All Treated Participants | Apparent Oral Clearance (CL/F) | Day 29 (n= 4, 2, 5, 5, 7, 6) | 27.32 Liter/hr (L/hr) |
| All Treated Participants | Apparent Oral Clearance (CL/F) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 19.80 Liter/hr (L/hr) |
| Cohort 2: Axitinib 20 mg BID, Fed | Apparent Oral Clearance (CL/F) | Day 29 (n= 4, 2, 5, 5, 7, 6) | 18.82 Liter/hr (L/hr) |
| Cohort 2: Axitinib 20 mg BID, Fed | Apparent Oral Clearance (CL/F) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 32.69 Liter/hr (L/hr) |
| Cohort 2: Axitinib 20 mg BID, Fed | Apparent Oral Clearance (CL/F) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 30.82 Liter/hr (L/hr) |
| Cohort 3: Axitinib 5 mg BID, Fed | Apparent Oral Clearance (CL/F) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 38.29 Liter/hr (L/hr) |
| Cohort 3: Axitinib 5 mg BID, Fed | Apparent Oral Clearance (CL/F) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 53.17 Liter/hr (L/hr) |
| Cohort 3: Axitinib 5 mg BID, Fed | Apparent Oral Clearance (CL/F) | Day 29 (n= 4, 2, 5, 5, 7, 6) | 34.69 Liter/hr (L/hr) |
| Cohort 4: Axitinib 15 mg QD, Fed | Apparent Oral Clearance (CL/F) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 30.61 Liter/hr (L/hr) |
| Cohort 4: Axitinib 15 mg QD, Fed | Apparent Oral Clearance (CL/F) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 29.04 Liter/hr (L/hr) |
| Cohort 4: Axitinib 15 mg QD, Fed | Apparent Oral Clearance (CL/F) | Day 29 (n= 4, 2, 5, 5, 7, 6) | 31.07 Liter/hr (L/hr) |
| Cohort 5: Axitinib 5 mg BID, Fasted | Apparent Oral Clearance (CL/F) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 39.05 Liter/hr (L/hr) |
| Cohort 5: Axitinib 5 mg BID, Fasted | Apparent Oral Clearance (CL/F) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 71.82 Liter/hr (L/hr) |
| Cohort 5: Axitinib 5 mg BID, Fasted | Apparent Oral Clearance (CL/F) | Day 29 (n= 4, 2, 5, 5, 7, 6) | 38.51 Liter/hr (L/hr) |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Apparent Oral Clearance (CL/F) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 30.27 Liter/hr (L/hr) |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Apparent Oral Clearance (CL/F) | Day 29 (n= 4, 2, 5, 5, 7, 6) | 19.73 Liter/hr (L/hr) |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Apparent Oral Clearance (CL/F) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 22.93 Liter/hr (L/hr) |
Secondary
Apparent Oral Clearance (CL/F) in Fed State Versus Overnight Fasting
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Population: The actual mean values were not reported in the fed and fasted state because the food effect evaluation was conducted across different dose groups and hence it was not appropriate to report overall mean values in different doses as PK parameters change with dose.
Secondary
Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)]
AUC (0-12)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-12).
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Population: Analysis population included all enrolled participants who received at least one dose of the study drug. 'n' signifies those participants evaluated for this measure at specific time point for each cohort respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| All Treated Participants | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 1 (n= 6, 4, 6, 5, 8, 6) | 692.47 ng*hr/mL |
| All Treated Participants | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 29 (n= 4, 3, 5, 5, 7, 6) | 456.53 ng*hr/mL |
| All Treated Participants | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 15 (n= 6, 3, 5, 6, 6, 6) | 793.89 ng*hr/mL |
| Cohort 2: Axitinib 20 mg BID, Fed | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 1 (n= 6, 4, 6, 5, 8, 6) | 564.56 ng*hr/mL |
| Cohort 2: Axitinib 20 mg BID, Fed | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 15 (n= 6, 3, 5, 6, 6, 6) | 485.52 ng*hr/mL |
| Cohort 2: Axitinib 20 mg BID, Fed | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 29 (n= 4, 3, 5, 5, 7, 6) | 441.50 ng*hr/mL |
| Cohort 3: Axitinib 5 mg BID, Fed | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 1 (n= 6, 4, 6, 5, 8, 6) | 88.62 ng*hr/mL |
| Cohort 3: Axitinib 5 mg BID, Fed | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 15 (n= 6, 3, 5, 6, 6, 6) | 130.57 ng*hr/mL |
| Cohort 3: Axitinib 5 mg BID, Fed | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 29 (n= 4, 3, 5, 5, 7, 6) | 144.13 ng*hr/mL |
| Cohort 4: Axitinib 15 mg QD, Fed | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 15 (n= 6, 3, 5, 6, 6, 6) | 380.56 ng*hr/mL |
| Cohort 4: Axitinib 15 mg QD, Fed | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 1 (n= 6, 4, 6, 5, 8, 6) | 473.26 ng*hr/mL |
| Cohort 4: Axitinib 15 mg QD, Fed | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 29 (n= 4, 3, 5, 5, 7, 6) | 377.86 ng*hr/mL |
| Cohort 5: Axitinib 5 mg BID, Fasted | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 29 (n= 4, 3, 5, 5, 7, 6) | 126.08 ng*hr/mL |
| Cohort 5: Axitinib 5 mg BID, Fasted | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 1 (n= 6, 4, 6, 5, 8, 6) | 68.73 ng*hr/mL |
| Cohort 5: Axitinib 5 mg BID, Fasted | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 15 (n= 6, 3, 5, 6, 6, 6) | 126.25 ng*hr/mL |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 29 (n= 4, 3, 5, 5, 7, 6) | 253.45 ng*hr/mL |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 1 (n= 6, 4, 6, 5, 8, 6) | 61.92 ng*hr/mL |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] | Day 15 (n= 6, 3, 5, 6, 6, 6) | 218.05 ng*hr/mL |
Secondary
Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] in Fed State Versus Overnight Fasting
AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Population: The actual mean values were not reported in the fed and fasted state because the food effect evaluation was conducted across different dose groups and hence it was not appropriate to report overall mean values in different doses as PK parameters change with dose.
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours (hrs) post-dose on Day (D) 1 and 15 of Cycle (C) 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Population: Analysis population included all enrolled participants who received at least one dose of the study drug.'n' signifies those participants evaluated for this measure at specific time point for each cohort respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| All Treated Participants | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 130.91 Nanogram/milliliter (ng/mL) | Standard Deviation 60.23 |
| All Treated Participants | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 144.48 Nanogram/milliliter (ng/mL) | Standard Deviation 73.9 |
| All Treated Participants | Maximum Observed Plasma Concentration (Cmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 76.25 Nanogram/milliliter (ng/mL) | Standard Deviation 67.86 |
| Cohort 2: Axitinib 20 mg BID, Fed | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 94.75 Nanogram/milliliter (ng/mL) | Standard Deviation 110.81 |
| Cohort 2: Axitinib 20 mg BID, Fed | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 97.81 Nanogram/milliliter (ng/mL) | Standard Deviation 89.96 |
| Cohort 2: Axitinib 20 mg BID, Fed | Maximum Observed Plasma Concentration (Cmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 69.14 Nanogram/milliliter (ng/mL) | Standard Deviation 103.14 |
| Cohort 3: Axitinib 5 mg BID, Fed | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 28.68 Nanogram/milliliter (ng/mL) | Standard Deviation 8.33 |
| Cohort 3: Axitinib 5 mg BID, Fed | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 20.71 Nanogram/milliliter (ng/mL) | Standard Deviation 9.48 |
| Cohort 3: Axitinib 5 mg BID, Fed | Maximum Observed Plasma Concentration (Cmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 26.44 Nanogram/milliliter (ng/mL) | Standard Deviation 17.28 |
| Cohort 4: Axitinib 15 mg QD, Fed | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 67.08 Nanogram/milliliter (ng/mL) | Standard Deviation 42.5 |
| Cohort 4: Axitinib 15 mg QD, Fed | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 88.16 Nanogram/milliliter (ng/mL) | Standard Deviation 84.93 |
| Cohort 4: Axitinib 15 mg QD, Fed | Maximum Observed Plasma Concentration (Cmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 60.11 Nanogram/milliliter (ng/mL) | Standard Deviation 103.76 |
| Cohort 5: Axitinib 5 mg BID, Fasted | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 51.82 Nanogram/milliliter (ng/mL) | Standard Deviation 31.21 |
| Cohort 5: Axitinib 5 mg BID, Fasted | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 22.21 Nanogram/milliliter (ng/mL) | Standard Deviation 34.88 |
| Cohort 5: Axitinib 5 mg BID, Fasted | Maximum Observed Plasma Concentration (Cmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 43.28 Nanogram/milliliter (ng/mL) | Standard Deviation 41.41 |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 19.75 Nanogram/milliliter (ng/mL) | Standard Deviation 17.95 |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Maximum Observed Plasma Concentration (Cmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 60.48 Nanogram/milliliter (ng/mL) | Standard Deviation 29.1 |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 52.24 Nanogram/milliliter (ng/mL) | Standard Deviation 53.87 |
Secondary
Maximum Observed Plasma Concentration (Cmax) in Fed State Versus Overnight Fasting
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Population: The actual mean values were not reported in the fed and fasted state because the food effect evaluation was conducted across different dose groups and hence it was not appropriate to report overall mean values in different doses as PK parameters change with dose.
Secondary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Population: Analysis population included all enrolled participants who received at least one dose of the study drug. 'n' signifies those participants evaluated for this measure at specific time point for each cohort respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Treated Participants | Plasma Decay Half-Life (t1/2) | Day 15 (n= 5, 3, 5, 4, 5, 6) | 5.20 hr | Standard Deviation 3.12 |
| All Treated Participants | Plasma Decay Half-Life (t1/2) | Day 1 (n= 6, 3, 5, 5, 5, 4) | 3.09 hr | Standard Deviation 1 |
| All Treated Participants | Plasma Decay Half-Life (t1/2) | Day 29 (n= 3, 2, 5, 3, 6, 6) | 6.11 hr | Standard Deviation 4.23 |
| Cohort 2: Axitinib 20 mg BID, Fed | Plasma Decay Half-Life (t1/2) | Day 15 (n= 5, 3, 5, 4, 5, 6) | 3.17 hr | Standard Deviation 1.71 |
| Cohort 2: Axitinib 20 mg BID, Fed | Plasma Decay Half-Life (t1/2) | Day 1 (n= 6, 3, 5, 5, 5, 4) | 3.29 hr | Standard Deviation 1.86 |
| Cohort 2: Axitinib 20 mg BID, Fed | Plasma Decay Half-Life (t1/2) | Day 29 (n= 3, 2, 5, 3, 6, 6) | 3.94 hr | Standard Deviation 2.65 |
| Cohort 3: Axitinib 5 mg BID, Fed | Plasma Decay Half-Life (t1/2) | Day 29 (n= 3, 2, 5, 3, 6, 6) | 2.78 hr | Standard Deviation 0.8 |
| Cohort 3: Axitinib 5 mg BID, Fed | Plasma Decay Half-Life (t1/2) | Day 1 (n= 6, 3, 5, 5, 5, 4) | 2.31 hr | Standard Deviation 0.64 |
| Cohort 3: Axitinib 5 mg BID, Fed | Plasma Decay Half-Life (t1/2) | Day 15 (n= 5, 3, 5, 4, 5, 6) | 2.22 hr | Standard Deviation 0.34 |
| Cohort 4: Axitinib 15 mg QD, Fed | Plasma Decay Half-Life (t1/2) | Day 29 (n= 3, 2, 5, 3, 6, 6) | 2.16 hr | Standard Deviation 0.79 |
| Cohort 4: Axitinib 15 mg QD, Fed | Plasma Decay Half-Life (t1/2) | Day 15 (n= 5, 3, 5, 4, 5, 6) | 2.48 hr | Standard Deviation 0.68 |
| Cohort 4: Axitinib 15 mg QD, Fed | Plasma Decay Half-Life (t1/2) | Day 1 (n= 6, 3, 5, 5, 5, 4) | 3.08 hr | Standard Deviation 0.97 |
| Cohort 5: Axitinib 5 mg BID, Fasted | Plasma Decay Half-Life (t1/2) | Day 29 (n= 3, 2, 5, 3, 6, 6) | 3.03 hr | Standard Deviation 0.74 |
| Cohort 5: Axitinib 5 mg BID, Fasted | Plasma Decay Half-Life (t1/2) | Day 1 (n= 6, 3, 5, 5, 5, 4) | 1.86 hr | Standard Deviation 0.44 |
| Cohort 5: Axitinib 5 mg BID, Fasted | Plasma Decay Half-Life (t1/2) | Day 15 (n= 5, 3, 5, 4, 5, 6) | 2.01 hr | Standard Deviation 1.23 |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Plasma Decay Half-Life (t1/2) | Day 1 (n= 6, 3, 5, 5, 5, 4) | 3.77 hr | Standard Deviation 1.6 |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Plasma Decay Half-Life (t1/2) | Day 29 (n= 3, 2, 5, 3, 6, 6) | 3.33 hr | Standard Deviation 0.9 |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Plasma Decay Half-Life (t1/2) | Day 15 (n= 5, 3, 5, 4, 5, 6) | 5.78 hr | Standard Deviation 6.33 |
Secondary
Plasma Decay Half-Life (t1/2) in Fed State Versus Overnight Fasting
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Population: The actual mean values were not reported in the fed and fasted state because the food effect evaluation was conducted across different dose groups and hence it was not appropriate to report overall mean values in different doses as PK parameters change with dose.
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3)
Population: Analysis population included all enrolled participants who received at least one dose of the study drug. 'n' signifies those participants evaluated for this measure at specific time point for each cohort respectively.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| All Treated Participants | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 3.00 hr |
| All Treated Participants | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 2.00 hr |
| All Treated Participants | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 3.44 hr |
| Cohort 2: Axitinib 20 mg BID, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 3.95 hr |
| Cohort 2: Axitinib 20 mg BID, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 4.04 hr |
| Cohort 2: Axitinib 20 mg BID, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 4.13 hr |
| Cohort 3: Axitinib 5 mg BID, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 2.00 hr |
| Cohort 3: Axitinib 5 mg BID, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 4.00 hr |
| Cohort 3: Axitinib 5 mg BID, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 2.00 hr |
| Cohort 4: Axitinib 15 mg QD, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 4.00 hr |
| Cohort 4: Axitinib 15 mg QD, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 2.05 hr |
| Cohort 4: Axitinib 15 mg QD, Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 3.50 hr |
| Cohort 5: Axitinib 5 mg BID, Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 1.01 hr |
| Cohort 5: Axitinib 5 mg BID, Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 1.52 hr |
| Cohort 5: Axitinib 5 mg BID, Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 1.00 hr |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n= 6, 4, 6, 5, 8, 6) | 1.01 hr |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 29 (n= 4, 3, 5, 5, 7, 6) | 2.01 hr |
| Cohort 6: Axitinib 2 mg + 5 mg BID, Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n= 6, 3, 5, 6, 6, 6) | 1.51 hr |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) in Fed State Versus Overnight Fasting
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2)
Population: The actual mean values were not reported in the fed and fasted state because the food effect evaluation was conducted across different dose groups and hence it was not appropriate to report overall mean values in different doses as PK parameters change with dose.