Tumors
Conditions
Keywords
Solid tumors
Brief summary
The primary purpose of this trial is to determine the maximum tolerated dose (MTD), or the maximum acceptable dose (MAD) and evaluate the dose limiting toxicity (DLT) of oral suberoylanilide hydroxamic acid in participants with solid tumors.
Interventions
DRUGvorinostat
vorinostat 100 mg, 200 mg, 400 mg, or 500 mg single oral dose; once-daily or twice-daily administration
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants with histologically or cytologically diagnosed solid tumor; no standard therapy available or participant has failed to respond to standard therapy
Exclusion criteria
* Participants with history of immunotherapy, radiotherapy, surgery, or chemotherapy during the previous 4 weeks; previous treatment is 5 or more chemotherapeutic regimens. * Any uncontrolled concomitant illness * Are pregnant or breast-feeding * Serious drug or food allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced One or More Adverse Events | Up to approximately 4 years | An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | Up to approximately 4 years | An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1 | Up to 26 days | A DLT was defined as an event considered to be related to study treatment and included: 1) Grade 4 neutropenia refractory to treatments persisting more than 5 days; 2) Grade 3 or more severe neutropenic fever; 3) Grade 3 thrombocytopenia requiring blood transfusions or Grade 4 thrombocytopenia; 4) Grade 4 hemoglobin decrease; 5) Grade 3 or more severe non-hematological toxicities other than anorexia, nausea/vomiting, and fatigue. (For the diarrhea, it was defined as not to use the frequency for the grading. For the alanine aminotransferase \[ALT\]/aspartate aminotransferase \[AST\]), it was defined as the case of over 300 IU/L; 6) Grade 3 or more severe anorexia, nausea/vomiting, and fatigue refractory to treatments; and 7) compliance of the study drug, while administrating 14 consecutive days, was less than 50% due to the drug-related adverse experience. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) of Vorinostat After a Single Oral Dose in a Fasted State | Day 1: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. |
| Cmax of Vorinostat After a Single Oral Dose in a Fed State | Day 3: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. |
| Cmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. |
| Time to Maximum Concentration (Tmax) of Vorinostat After a Single Oral Dose in a Fasted State | Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. |
| Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of Vorinostat After a Single Oral Dose in a Fasted State | Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. |
| Tmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. |
| Apparent Terminal Half-Life (t½) of Vorinostat After a Single Oral Dose in a Fasted State | Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | t½ is the elimination half-life of study drug. t½ is the time it takes for half of the study drug in the blood plasma to dissipate. |
| t½ of Vorinostat After a Single Oral Dose in a Fed State | Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | t½ is the elimination half-life of study drug. t½ is the time it takes for half of the study drug in the blood plasma to dissipate. |
| t½ of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | t½ is the elimination half-life of study drug. t½ is the time it takes for half of the study drug in the blood plasma to dissipate. |
| Tmax of Vorinostat After a Single Oral Dose in a Fed State | Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. |
| AUC0-Inf of Vorinostat After a Single Oral Dose in a Fed State | Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. |
| AUC0-inf of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose | AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vorinostat 100 mg During Cycle 1, participants received a single oral dose of vorinostat 100 mg on Day 1 (fasted), Day 3 (fed), and Day 19 (fed). On Days 5-18, participants received vorinostat 100 mg twice daily, in the morning and evening. If participants did not match to the discontinuation criteria, they could continue the same dose level therapy during Cycle 2 and subsequent cycles. (Each cycle was 26 days.) | 3 |
| Vorinostat 200 mg During Cycle 1, participants received a single oral dose of vorinostat 200 mg on Day 1 (fasted), Day 3 (fed), and Day 19 (fed). On Days 5-18, participants received vorinostat 200 mg twice daily, in the morning and evening. If participants did not match to the discontinuation criteria, they could continue the same dose level therapy during Cycle 2 and subsequent cycles. (Each cycle was 26 days.) | 6 |
| Vorinostat 400 mg During Cycle 1, participants received a single oral dose of vorinostat 400 mg on Day 1 (fasted), Day 3 (fed), Day 19 (fed). On Days 5-18, participants received a single oral dose of vorinostat 400 mg once-daily in the morning. If participants did not match to the discontinuation criteria, they could continue the same dose level therapy during Cycle 2 and subsequent cycles. (Each cycle was 26 days.) | 3 |
| Vorinostat 500 mg During Cycle 1, participants received a single oral dose of vorinostat 500 mg on Day 1 (fasted), Day 3 (fed), Day 19 (fed). On Days 5-18, participants received a single oral dose of vorinostat 500 mg once-daily in the morning. If participants did not match to the discontinuation criteria, they could continue the same dose level therapy on the Cycle 2 and subsequent cycles.(Each cycle was 26 days.) | 6 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 3 | 0 | 2 |
Baseline characteristics
| Characteristic | Vorinostat 100 mg | Total | Vorinostat 500 mg | Vorinostat 400 mg | Vorinostat 200 mg |
|---|---|---|---|---|---|
| Age, Continuous | 59.7 Years STANDARD_DEVIATION 6.7 | 57.6 Years STANDARD_DEVIATION 10.4 | 57.7 Years STANDARD_DEVIATION 8.3 | 49.3 Years STANDARD_DEVIATION 21.5 | 60.5 Years STANDARD_DEVIATION 6.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 18 Participants | 6 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 15 Participants | 6 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 6 |
| other Total, other adverse events | 4 / 4 | 6 / 6 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 0 / 4 | 1 / 6 | 1 / 3 | 0 / 6 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: Up to approximately 4 years
Population: All participants who received at least one dose of study drug. (Note: 1 participant in 200 mg treatment group had dose reduced to 100 mg in Cycle 8 and is also included in 100 mg treatment group for adverse events.)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vorinostat 100 mg | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0 Participants |
| Vorinostat 200 mg | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 1 Participants |
| Vorinostat 400 mg | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0 Participants |
| Vorinostat 500 mg | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 1 Participants |
Primary
Number of Participants Who Experienced One or More Adverse Events
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: Up to approximately 4 years
Population: All participants who received at least one dose of study drug. (Note: 1 participant in 200 mg treatment group had dose reduced to 100 mg in Cycle 8 and is also included in 100 mg treatment group for adverse events.)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vorinostat 100 mg | Number of Participants Who Experienced One or More Adverse Events | 4 Participants |
| Vorinostat 200 mg | Number of Participants Who Experienced One or More Adverse Events | 6 Participants |
| Vorinostat 400 mg | Number of Participants Who Experienced One or More Adverse Events | 3 Participants |
| Vorinostat 500 mg | Number of Participants Who Experienced One or More Adverse Events | 6 Participants |
Primary
Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1
A DLT was defined as an event considered to be related to study treatment and included: 1) Grade 4 neutropenia refractory to treatments persisting more than 5 days; 2) Grade 3 or more severe neutropenic fever; 3) Grade 3 thrombocytopenia requiring blood transfusions or Grade 4 thrombocytopenia; 4) Grade 4 hemoglobin decrease; 5) Grade 3 or more severe non-hematological toxicities other than anorexia, nausea/vomiting, and fatigue. (For the diarrhea, it was defined as not to use the frequency for the grading. For the alanine aminotransferase \[ALT\]/aspartate aminotransferase \[AST\]), it was defined as the case of over 300 IU/L; 6) Grade 3 or more severe anorexia, nausea/vomiting, and fatigue refractory to treatments; and 7) compliance of the study drug, while administrating 14 consecutive days, was less than 50% due to the drug-related adverse experience.
Time frame: Up to 26 days
Population: All participants who received at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vorinostat 100 mg | Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1 | 0 Participants |
| Vorinostat 200 mg | Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1 | 3 Participants |
| Vorinostat 400 mg | Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1 | 0 Participants |
| Vorinostat 500 mg | Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1 | 2 Participants |
Secondary
Apparent Terminal Half-Life (t½) of Vorinostat After a Single Oral Dose in a Fasted State
t½ is the elimination half-life of study drug. t½ is the time it takes for half of the study drug in the blood plasma to dissipate.
Time frame: Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had Day 1 PK data for t½
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | Apparent Terminal Half-Life (t½) of Vorinostat After a Single Oral Dose in a Fasted State | 1.08 Hours | Standard Deviation 0.3 |
| Vorinostat 200 mg | Apparent Terminal Half-Life (t½) of Vorinostat After a Single Oral Dose in a Fasted State | 1.83 Hours | Standard Deviation 0.53 |
| Vorinostat 400 mg | Apparent Terminal Half-Life (t½) of Vorinostat After a Single Oral Dose in a Fasted State | 1.90 Hours | Standard Deviation 0.72 |
| Vorinostat 500 mg | Apparent Terminal Half-Life (t½) of Vorinostat After a Single Oral Dose in a Fasted State | 1.93 Hours | Standard Deviation 0.67 |
Secondary
Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of Vorinostat After a Single Oral Dose in a Fasted State
AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Time frame: Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had Day 1 pharmacokinetic (PK) data for AUC0-inf.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of Vorinostat After a Single Oral Dose in a Fasted State | 1.20 μM·hours | Standard Deviation 0.27 |
| Vorinostat 200 mg | Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of Vorinostat After a Single Oral Dose in a Fasted State | 2.31 μM·hours | Standard Deviation 0.96 |
| Vorinostat 400 mg | Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of Vorinostat After a Single Oral Dose in a Fasted State | 3.96 μM·hours | Standard Deviation 1.62 |
| Vorinostat 500 mg | Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of Vorinostat After a Single Oral Dose in a Fasted State | 3.47 μM·hours | Standard Deviation 2.21 |
Secondary
AUC0-inf of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration
AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Time frame: Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had up to Day 19 PK data for AUC0-inf
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | AUC0-inf of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 1.33 μM·hours | Standard Deviation 0.23 |
| Vorinostat 200 mg | AUC0-inf of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 2.76 μM·hours | Standard Deviation 0.85 |
| Vorinostat 400 mg | AUC0-inf of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 5.41 μM·hours | Standard Deviation 2.18 |
| Vorinostat 500 mg | AUC0-inf of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 6.33 μM·hours | Standard Deviation 1.53 |
Secondary
AUC0-Inf of Vorinostat After a Single Oral Dose in a Fed State
AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Time frame: Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had Day 3 PK data for AUC0-inf.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | AUC0-Inf of Vorinostat After a Single Oral Dose in a Fed State | 0.98 μM·hours | Standard Deviation 0.07 |
| Vorinostat 200 mg | AUC0-Inf of Vorinostat After a Single Oral Dose in a Fed State | 2.22 μM·hours | Standard Deviation 0.89 |
| Vorinostat 400 mg | AUC0-Inf of Vorinostat After a Single Oral Dose in a Fed State | 4.30 μM·hours | Standard Deviation 0.37 |
| Vorinostat 500 mg | AUC0-Inf of Vorinostat After a Single Oral Dose in a Fed State | 5.93 μM·hours | Standard Deviation 1.78 |
Secondary
Cmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Time frame: Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had up to Day 19 PK data for Cmax
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | Cmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 0.29 μM | Standard Deviation 0.25 |
| Vorinostat 200 mg | Cmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 0.84 μM | Standard Deviation 0.56 |
| Vorinostat 400 mg | Cmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 0.86 μM | Standard Deviation 0.61 |
| Vorinostat 500 mg | Cmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 1.09 μM | Standard Deviation 0.3 |
Secondary
Cmax of Vorinostat After a Single Oral Dose in a Fed State
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Time frame: Day 3: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had Day 3 PK data for Cmax
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | Cmax of Vorinostat After a Single Oral Dose in a Fed State | 0.21 μM | Standard Deviation 0.14 |
| Vorinostat 200 mg | Cmax of Vorinostat After a Single Oral Dose in a Fed State | 0.59 μM | Standard Deviation 0.22 |
| Vorinostat 400 mg | Cmax of Vorinostat After a Single Oral Dose in a Fed State | 0.93 μM | Standard Deviation 0.12 |
| Vorinostat 500 mg | Cmax of Vorinostat After a Single Oral Dose in a Fed State | 1.35 μM | Standard Deviation 0.39 |
Secondary
Maximum Concentration (Cmax) of Vorinostat After a Single Oral Dose in a Fasted State
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.
Time frame: Day 1: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had Day 1 PK data for Cmax
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | Maximum Concentration (Cmax) of Vorinostat After a Single Oral Dose in a Fasted State | 0.49 μM | Standard Deviation 0.15 |
| Vorinostat 200 mg | Maximum Concentration (Cmax) of Vorinostat After a Single Oral Dose in a Fasted State | 0.77 μM | Standard Deviation 0.13 |
| Vorinostat 400 mg | Maximum Concentration (Cmax) of Vorinostat After a Single Oral Dose in a Fasted State | 1.19 μM | Standard Deviation 0.2 |
| Vorinostat 500 mg | Maximum Concentration (Cmax) of Vorinostat After a Single Oral Dose in a Fasted State | 1.06 μM | Standard Deviation 0.52 |
Secondary
t½ of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration
t½ is the elimination half-life of study drug. t½ is the time it takes for half of the study drug in the blood plasma to dissipate.
Time frame: Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had up to Day 19 PK data for t½
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | t½ of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 1.95 Hours | Standard Deviation 0.54 |
| Vorinostat 200 mg | t½ of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 1.42 Hours | Standard Deviation 0.5 |
| Vorinostat 400 mg | t½ of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 1.98 Hours | Standard Deviation 1.56 |
| Vorinostat 500 mg | t½ of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 1.30 Hours | Standard Deviation 0.41 |
Secondary
t½ of Vorinostat After a Single Oral Dose in a Fed State
t½ is the elimination half-life of study drug. t½ is the time it takes for half of the study drug in the blood plasma to dissipate.
Time frame: Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had Day 3 PK data for t½
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | t½ of Vorinostat After a Single Oral Dose in a Fed State | 1.62 Hours | Standard Deviation 0.45 |
| Vorinostat 200 mg | t½ of Vorinostat After a Single Oral Dose in a Fed State | 1.36 Hours | Standard Deviation 0.28 |
| Vorinostat 400 mg | t½ of Vorinostat After a Single Oral Dose in a Fed State | 2.01 Hours | Standard Deviation 1.47 |
| Vorinostat 500 mg | t½ of Vorinostat After a Single Oral Dose in a Fed State | 1.60 Hours | Standard Deviation 0.66 |
Secondary
Time to Maximum Concentration (Tmax) of Vorinostat After a Single Oral Dose in a Fasted State
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose.
Time frame: Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had Day 1 PK data for Tmax
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | Time to Maximum Concentration (Tmax) of Vorinostat After a Single Oral Dose in a Fasted State | 0.84 Hours | Standard Deviation 0.3 |
| Vorinostat 200 mg | Time to Maximum Concentration (Tmax) of Vorinostat After a Single Oral Dose in a Fasted State | 1.59 Hours | Standard Deviation 0.74 |
| Vorinostat 400 mg | Time to Maximum Concentration (Tmax) of Vorinostat After a Single Oral Dose in a Fasted State | 2.49 Hours | Standard Deviation 0.86 |
| Vorinostat 500 mg | Time to Maximum Concentration (Tmax) of Vorinostat After a Single Oral Dose in a Fasted State | 1.91 Hours | Standard Deviation 0.91 |
Secondary
Tmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose.
Time frame: Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had up to Day 19 PK data for Tmax
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | Tmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 4.66 Hours | Standard Deviation 1.16 |
| Vorinostat 200 mg | Tmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 3.30 Hours | Standard Deviation 1.1 |
| Vorinostat 400 mg | Tmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 4.34 Hours | Standard Deviation 1.53 |
| Vorinostat 500 mg | Tmax of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration | 4.61 Hours | Standard Deviation 1.95 |
Secondary
Tmax of Vorinostat After a Single Oral Dose in a Fed State
Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose.
Time frame: Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose
Population: All participants who complied with the protocol and had Day 3 PK data for Tmax
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vorinostat 100 mg | Tmax of Vorinostat After a Single Oral Dose in a Fed State | 5.66 Hours | Standard Deviation 3.79 |
| Vorinostat 200 mg | Tmax of Vorinostat After a Single Oral Dose in a Fed State | 3.00 Hours | Standard Deviation 0.89 |
| Vorinostat 400 mg | Tmax of Vorinostat After a Single Oral Dose in a Fed State | 3.53 Hours | Standard Deviation 2.33 |
| Vorinostat 500 mg | Tmax of Vorinostat After a Single Oral Dose in a Fed State | 3.17 Hours | Standard Deviation 1.17 |