Neoplasm
Conditions
Keywords
PPARγ agonist, advanced or metastatic malignancies, Tumor, Cancer
Brief summary
An open-label, Phase I, dose escalation study of CS-7017 administered by mouth in sequential cohorts of 3 to 6 participants with advanced or metastatic malignancies.
Interventions
DRUGCS-7017
CS-7017 0.05mg and 1.0mg tablets
Sponsors
Daiichi Sankyo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically diagnosed advanced or metastatic malignancy that is refractory to, not curable with, or not eligible for standard treatment(s). * 18 years or older * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. * Resolution of any toxic effects of prior therapy (except alopecia) to National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grade less than or equal to 1. * Adequate organ and bone marrow function. * Willing to use effective contraceptive while on treatment through at least 3 months thereafter. * Negative pregnancy test for females of childbearing potential. * Echocardiogram with ejection fraction within normal range.
Exclusion criteria
* Anticipation of need for a major surgical procedure or radiation therapy during the study. * Treatment with chemotherapy, hormonal therapy, other thiazolidinediones, radiotherapy, minor surgery, or any investigational agent within 4 weeks (6 weeks for nitrosoureas, mitomycin C, immunotherapy, biological therapy, or major surgery) of study treatment start. * Participants with clinically significant pleural or pericardial effusion (participants with minimal pleural effusion may be eligible at the Investigator's discretion). * Clinically significant active infection, which requires antibiotic therapy, or human immunodeficiency virus (HIV)-positive participants receiving antiretroviral therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Baseline up to at least 2 cycles (each cycle was 3 weeks), up to 2 years 5 months | Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions). Objective response rate was defined as the sum of all CRs and PRs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1. | Area under the plasma/serum drug concentration-time curve for dosing interval (AUC\[0-tau\]), computed using the linear trapezoidal rule and area under the plasma/serum drug concentration-time curve from 0 to last time point above the quantification limit (AUC\[0-t\]) calculated using the linear trapezoidal rule were assessed. |
| Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1. | Cmax was defined as observed maximum plasma concentration. |
| Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1. | — |
| Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1. | Tmax was defined as time of maximum plasma concentration. |
Countries
United States
Participant flow
Recruitment details
A total of 32 participants who met all inclusion criteria and no exclusion criteria were enrolled in study from 20 November 2006 to 03 April 2009 at 2 clinic sites in the United States. Of the 32 participants enrolled, 31 participants were dosed and received treatment.
Pre-assignment details
Participants received CS-7017 (0.10 mg to 1.15 mg) every 12 hours. At least 3 participants were treated at each dose level. Dose escalation occurred after at least 3 participants in the current dosing cohort completed 1 cycle of treatment (3 weeks).
Participants by arm
| Arm | Count |
|---|---|
| CS-7017 0.10 mg Participants who received oral CS-7017 0.10 mg every 12 hours. | 6 |
| CS-7017 0.15 mg Participants who received oral CS-7017 0.15 mg every 12 hours. | 3 |
| CS-7017 0.25 mg Participants who received oral CS-7017 0.25 mg every 12 hours. | 6 |
| CS-7017 0.35 mg Participants who received oral CS-7017 0.35 mg every 12 hours. | 3 |
| CS-7017 0.50 mg Participants who received oral CS-7017 0.50 mg every 12 hours. | 6 |
| CS-7017 0.75 mg Participants who received oral CS-7017 0.75 mg every 12 hours. | 3 |
| CS-7017 1.15 mg Participants who received oral CS-7017 1.15 mg every 12 hours. | 4 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 1 | 0 | 2 | 1 | 0 |
| Overall Study | Progressive disease | 6 | 3 | 4 | 3 | 3 | 1 | 4 |
| Overall Study | Terminated by Investigator | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | CS-7017 0.10 mg | CS-7017 0.15 mg | CS-7017 0.25 mg | CS-7017 0.35 mg | CS-7017 0.50 mg | CS-7017 0.75 mg | CS-7017 1.15 mg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.7 years STANDARD_DEVIATION 8.2 | 57.0 years STANDARD_DEVIATION 14.7 | 58.7 years STANDARD_DEVIATION 8.8 | 58.7 years STANDARD_DEVIATION 13.7 | 62.3 years STANDARD_DEVIATION 8.6 | 52.3 years STANDARD_DEVIATION 11.1 | 53.5 years STANDARD_DEVIATION 7.6 | 58.1 years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 3 Participants | 6 Participants | 1 Participants | 6 Participants | 3 Participants | 4 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 6 participants | 3 participants | 6 participants | 3 participants | 6 participants | 3 participants | 4 participants | 31 participants |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 4 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 6 | 2 / 3 | 0 / 6 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 6 / 6 | 3 / 3 | 6 / 6 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 3 / 6 | 0 / 3 | 2 / 6 | 2 / 3 | 3 / 6 | 0 / 3 | 1 / 4 |
Outcome results
Primary
Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies
Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions). Objective response rate was defined as the sum of all CRs and PRs.
Time frame: Baseline up to at least 2 cycles (each cycle was 3 weeks), up to 2 years 5 months
Population: Best overall response was assessed in the Efficacy Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CS-7017 0.10 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Progressive disease (PD) | 3 Participants |
| CS-7017 0.10 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Objective response rate (CR+PR) | 0 Participants |
| CS-7017 0.10 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Complete response (CR) | 0 Participants |
| CS-7017 0.10 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Stable disease (SD) | 3 Participants |
| CS-7017 0.10 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Partial response (PR) | 0 Participants |
| CS-7017 0.15 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Partial response (PR) | 0 Participants |
| CS-7017 0.15 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Progressive disease (PD) | 1 Participants |
| CS-7017 0.15 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Complete response (CR) | 0 Participants |
| CS-7017 0.15 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Stable disease (SD) | 2 Participants |
| CS-7017 0.15 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Objective response rate (CR+PR) | 0 Participants |
| CS-7017 0.25 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Complete response (CR) | 0 Participants |
| CS-7017 0.25 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Objective response rate (CR+PR) | 0 Participants |
| CS-7017 0.25 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Partial response (PR) | 0 Participants |
| CS-7017 0.25 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Progressive disease (PD) | 4 Participants |
| CS-7017 0.25 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Stable disease (SD) | 0 Participants |
| CS-7017 0.35 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Stable disease (SD) | 1 Participants |
| CS-7017 0.35 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Objective response rate (CR+PR) | 0 Participants |
| CS-7017 0.35 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Complete response (CR) | 0 Participants |
| CS-7017 0.35 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Partial response (PR) | 0 Participants |
| CS-7017 0.35 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Progressive disease (PD) | 2 Participants |
| CS-7017 0.50 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Stable disease (SD) | 4 Participants |
| CS-7017 0.50 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Complete response (CR) | 0 Participants |
| CS-7017 0.50 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Partial response (PR) | 0 Participants |
| CS-7017 0.50 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Progressive disease (PD) | 1 Participants |
| CS-7017 0.50 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Objective response rate (CR+PR) | 0 Participants |
| CS-7017 0.75 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Stable disease (SD) | 1 Participants |
| CS-7017 0.75 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Progressive disease (PD) | 1 Participants |
| CS-7017 0.75 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Partial response (PR) | 1 Participants |
| CS-7017 0.75 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Complete response (CR) | 0 Participants |
| CS-7017 0.75 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Objective response rate (CR+PR) | 1 Participants |
| CS-7017 1.15 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Stable disease (SD) | 1 Participants |
| CS-7017 1.15 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Complete response (CR) | 0 Participants |
| CS-7017 1.15 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Partial response (PR) | 0 Participants |
| CS-7017 1.15 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Objective response rate (CR+PR) | 0 Participants |
| CS-7017 1.15 mg | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Progressive disease (PD) | 2 Participants |
| CS-7017 All Participants | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Objective response rate (CR+PR) | 1 Participants |
| CS-7017 All Participants | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Progressive disease (PD) | 14 Participants |
| CS-7017 All Participants | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Complete response (CR) | 0 Participants |
| CS-7017 All Participants | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Stable disease (SD) | 12 Participants |
| CS-7017 All Participants | Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | Partial response (PR) | 1 Participants |
Secondary
Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies
Area under the plasma/serum drug concentration-time curve for dosing interval (AUC\[0-tau\]), computed using the linear trapezoidal rule and area under the plasma/serum drug concentration-time curve from 0 to last time point above the quantification limit (AUC\[0-t\]) calculated using the linear trapezoidal rule were assessed.
Time frame: Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1.
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CS-7017 0.10 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-tau) | 23.05 ng*h/ml | Standard Deviation 6.11 |
| CS-7017 0.10 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-12) | 32.96 ng*h/ml | Standard Deviation 6.9 |
| CS-7017 0.15 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-tau) | 32.05 ng*h/ml | Standard Deviation 7.75 |
| CS-7017 0.15 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-12) | 44.14 ng*h/ml | Standard Deviation 12.15 |
| CS-7017 0.25 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-tau) | 68.33 ng*h/ml | Standard Deviation 24.61 |
| CS-7017 0.25 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-12) | 91.24 ng*h/ml | Standard Deviation 36.16 |
| CS-7017 0.35 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-tau) | 59.72 ng*h/ml | Standard Deviation 32.58 |
| CS-7017 0.35 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-12) | 80.80 ng*h/ml | Standard Deviation 40.74 |
| CS-7017 0.50 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-tau) | 159.2 ng*h/ml | Standard Deviation 45.1 |
| CS-7017 0.50 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-12) | 220.9 ng*h/ml | Standard Deviation 74.42 |
| CS-7017 0.75 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-tau) | 159.14 ng*h/ml | Standard Deviation 126.31 |
| CS-7017 0.75 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-12) | 214.38 ng*h/ml | Standard Deviation 163.81 |
| CS-7017 1.15 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-tau) | 256.3 ng*h/ml | Standard Deviation 93.31 |
| CS-7017 1.15 mg | Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies | AUC(0-12) | 356.8 ng*h/ml | Standard Deviation 127.69 |
Secondary
Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies
Cmax was defined as observed maximum plasma concentration.
Time frame: Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1.
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CS-7017 0.10 mg | Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 4.21 ng/ml | Standard Deviation 0.93 |
| CS-7017 0.15 mg | Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 5.76 ng/ml | Standard Deviation 1.53 |
| CS-7017 0.25 mg | Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 12.19 ng/ml | Standard Deviation 3 |
| CS-7017 0.35 mg | Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 12.26 ng/ml | Standard Deviation 7.1 |
| CS-7017 0.50 mg | Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 26.92 ng/ml | Standard Deviation 6.36 |
| CS-7017 0.75 mg | Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 27.64 ng/ml | Standard Deviation 21.44 |
| CS-7017 1.15 mg | Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 44.73 ng/ml | Standard Deviation 15.05 |
Secondary
Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies
Time frame: Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1.
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CS-7017 0.10 mg | Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 8.51 hour | Standard Deviation 3.92 |
| CS-7017 0.15 mg | Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 13.78 hour | Standard Deviation 6.92 |
| CS-7017 0.25 mg | Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 11.48 hour | Standard Deviation 11.3 |
| CS-7017 0.35 mg | Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 12.49 hour | Standard Deviation 7.35 |
| CS-7017 0.50 mg | Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 5.74 hour | Standard Deviation 2.56 |
| CS-7017 0.75 mg | Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 9.08 hour | Standard Deviation 2.79 |
| CS-7017 1.15 mg | Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 11.66 hour | Standard Deviation 3.45 |
Secondary
Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies
Tmax was defined as time of maximum plasma concentration.
Time frame: Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1.
Population: Pharmacokinetic parameters were assessed in the Pharmacokinetic Population.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CS-7017 0.10 mg | Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 3.00 hour |
| CS-7017 0.15 mg | Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 2.00 hour |
| CS-7017 0.25 mg | Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 1.58 hour |
| CS-7017 0.35 mg | Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 3.00 hour |
| CS-7017 0.50 mg | Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 2.00 hour |
| CS-7017 0.75 mg | Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 3.00 hour |
| CS-7017 1.15 mg | Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies | 2.50 hour |