Hematologic Malignancy, Malignant Lymphoma
Conditions
Keywords
ROMI-001, romi, Romidepsin, Istodax, advanced malignancy, PK, pharmacokinetics
Brief summary
The purpose of this study is to evaluate the effect and safety of multiple doses of ketoconazole on the pharmacokinetics of romidepsin after a single intravenous (IV) infusion.
Interventions
DRUGRomidepsin
Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8.
DRUGKetoconazole
Ketoconazole 400 mg oral once daily on Days 4-8
Sponsors
Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and females 18 years of age or older at the time of signing the informed consent document. 2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. Must have diagnosis of advanced malignancy and must have failed other available therapies considered standard of care for their disease. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 6. Negative urine or serum pregnancy test on females of childbearing potential; and 7. All females of childbearing potential must use an effective barrier method of contraception (either an intrauterine contraceptive device \[IUCD\] or double barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 1 month thereafter. Male subjects should use a barrier method of contraception during the treatment period and for at least 3 months thereafter. Female subjects should avoid the use of estrogen-containing contraceptives, since romidepsin may reduce the effectiveness of estrogen-containing contraceptives. An in vitro binding assay determined that romidepsin competes with β-estradiol for binding to estrogen receptors.
Exclusion criteria
1. Any significant medical condition or psychiatric illness that would prevent the subject from participating in the study. 2. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 3. Subjects with significant gastrointestinal disease that may impair drug absorption, such as subjects with a history of Cohn's disease, colectomy, gastrectomy, celiac disease, or other diseases with known malabsorption. 4. Serum potassium \< 3.8 mmol/L or serum magnesium \< 0.85 mmol/L (magnesium converts to 2.1 mg/dl or 1.7 mEq/L) (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria). 5. Concomitant use of drugs that may cause a significant prolongation of the corrected measurement of the time between the start of the cardiac Q wave and the end of the T wave (QTc). 6. Concomitant use of Cytochrome P 450 3A4 (CYP3A4) strong inhibitors within 1 week of trial medications. 7. Concomitant use of CYP3A4 strong inducers within 2 weeks of trial medications. 8. Concomitant use of therapeutic warfarin due to a potential drug interaction. Use of a low dose of warfarin or another anticoagulant to maintain patency of venous access port and cannulas is permitted. 9. Clinically significant active infection. 10. Known infection with Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C. 11. Inadequate bone marrow or other organ function as evidenced by: * Hemoglobin \< 9 g/dL (transfusions and/or erythropoietin are permitted); * Absolute neutrophil count (ANC) ≤ 1.0 \* 10\^9 cells/L \[subjects with neutropenia (ANC 1-1.5) as a function of their disease may be supported with granulocyte-colony stimulating factor (G-CSF)\]; * Platelet count \< 100 \* 10\^9 cells/L or platelet count \< 75 \* 10\^9 cells/L if bone marrow disease involvement is documented; * Total bilirubin \> 1.5 \* upper limit of normal (ULN) or \> 2.0 \* ULN in the presence of demonstrable liver metastases; * Serum aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) \> 1.5 \* ULN or \> 2.0 \* ULN in the presence of demonstrable liver metastases; or * Serum creatinine \> 2.0 \* ULN; 12. Prior chemotherapy treatment within 3 weeks prior to the first day of romidepsin treatment (6 weeks for nitrosoureas) or prior treatment with an investigational agent within 4 weeks prior to the first day of romidepsin treatment. 13. Prior radiotherapy within 4 weeks prior to the first day of treatment. Subjects who have not fully recovered or whose acute toxicity related to prior radiotherapy has not returned to baseline are ineligible. 14. Major surgery within 2 weeks of study entry (day 1). 15. Concomitant use of any other anti-cancer therapy. 16. Concomitant use of any investigational agent. 17. Prior exposure to romidepsin (other histone deacetylase\[HDAC\] inhibitors are allowed). 18. Any known cardiac abnormalities, such as: * Congenital long measure of the time between the start of the Q wave and the end of the T wave (QT) syndrome; * . Mean QTc formula (QTcF) interval \> 450 msec; * A myocardial infarction within 12 months of study entry; * A history of coronary artery disease (CAD), e.g., angina Canadian Class II-IV. A stress imaging study should be performed for any subject whose cardiac status is uncertain. If abnormal, an angiography should be completed to define whether or not CAD is present. * An electrocardiogram (ECG) recorded at screening showing evidence of cardiac ischemia (ST depression of ≥ 2 mm, measured from isoelectric line to ST segment). A stress imaging study should be performed for any subject whose cardiac status is uncertain. If abnormal, an angiography should be completed to define whether or not CAD is present. * Congestive Heart Failure (CHF) that meets the New York Heart Association (NYHA) Class II to IV definitions (see Appendix F) and/or ejection fraction \< 40% by multi gated acquisition (MUGA) scan or \< 50% by echocardiogram and/or magnetic resonance imaging (MRI); * A known history of sustained ventricular tachycardia(VT), ventricular fibrillation (VF), torsades de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD); * Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes (if in doubt, see ejection fraction criteria above); * Uncontrolled hypertension, i.e., blood pressure (BP) of ≥ 160/95; or * Any cardiac arrhythmia requiring anti-arrhythmic medication 19. Subjects who are pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Total Volume of Distribution (Vz) | Days 1 and 8, At 0 (predose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion. | Vz: apparent total volume of distribution, calculated as \[(CL)/λz\]. |
| Area Under the Plasma Concentration Time-curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t)of Romidepsin | Days 1 and 8; at 0 (pre-dose) 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion. | AUC0-t: area under the plasma concentration time-curve from Time 0 to the time of the last quantifiable concentration (Ct), calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing. For AUC0-t, an analysis of variance (ANOVA) model was used to estimate the ratio of geometric means and its 90% CI between romidepsin alone and romidepsin in the presence to ketoconazole. |
| Area Under the Plasma Concentration Time-curve From Time 0 to 24-hour (AUC 0-24) | Days 1 and 8; at 0 (predose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion | AUC 0-24: area under the plasma concentration time-curve from Time 0 to 24 hours, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing; for AUC 0-24 an analysis of variance (ANOVA) model was used to estimate the ratio of geometric means and its 90% confidence interval (CI) between romidepsin alone and romidepsin in the presence of ketoconazole |
| Area Under the Plasma Concentration Time-curve From Time 0 Extrapolated to Infinity (AUC0-∞) | Days 1 and 8; at 0 (pre-dose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion. | AUC0-∞: area under the plasma concentration time-curve from Time 0 extrapolated to infinity, calculated as \[AUCt + Ct/λz\]. |
| Maximum Observed Plasma Concentration (Cmax) | Days 1 and 8; at 0 (pre-dose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion. | Cmax: maximum observed plasma concentration, obtained directly from the observed concentration versus time data; for Cmax, an analysis of variance (ANOVA) model was used to estimate the ratio of geometric means and its 90% confidence interval (CI) between romidepsin alone and romidepsin in the presence of ketoconazole |
| Time to Maximum Observed Plasma Concentration (Tmax) | Days 1 and 8; at 0 (pre-dose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion. | Tmax: time to maximum observed Tmax, obtained directly from the observed concentration versus time data |
| Estimate of the Terminal Elimination Half-life in Plasma (t1/2) | Days 1 and 8; at 0 (pre-dose),1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion. | Terminal elimination half-life (t1/2) in plasma, was calculated as \[(ln 2)/λz\] |
| Apparent Total Plasma Clearance (CL) | Days 1 and 8; at 0 (pre-dose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion. | Apparent total plasma clearance, (CL) calculated as \[Dose/AUC 0-∞\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | Day 1 up to Day 36 (28 days after last treatment) | All 15 subjects in the safety population received at least 1 dose of romidepsin. AEs were considered related if assessed by the Investigator as possibly, probably or definitely related to study drug. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
The recruitment period occured over 6 months; the first participant enrolled on 01 July 2011; the last participant completed was 04 Jan 2012; 3 participating sites were involved (2 sites from the US and 1 in the UK); Overall, 15 subjects with advanced cancer were enrolled to ensure there was a minimum of 12 evaluable subjects
Participants by arm
| Arm | Count |
|---|---|
| Romidepsin and Ketoconazole Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 1 and Day 8.
Ketoconazole 400 mg oral once daily on Days 4-8 | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Disease Progression | 1 |
Baseline characteristics
| Characteristic | Romidepsin and Ketoconazole |
|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 11.5 |
| Body Surface Area (BSA) | 1.9 m^2 STANDARD_DEVIATION 0.24 |
| Eastern Cooperative Oncology Group Performance Status (ECOG) 0 = Fully Active | 7 Participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG) 1 = Restricted in physical strenuous activity | 8 Participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG) 2 = Ambulatory but unable to work | 0 Participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG) 3 = Limited Self Care | 0 Participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG) 4 = Completely Disabled | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 174.9 Centimeters STANDARD_DEVIATION 9.59 |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 12 Participants |
| Region of Enrollment United Kingdom | 6 Participants |
| Region of Enrollment United States | 9 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 11 Participants |
| Weight | 78.4 kilograms STANDARD_DEVIATION 18.77 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 4 / 15 |
Outcome results
Primary
Apparent Total Plasma Clearance (CL)
Apparent total plasma clearance, (CL) calculated as \[Dose/AUC 0-∞\].
Time frame: Days 1 and 8; at 0 (pre-dose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion.
Population: Assess the influence of multiple doses of ketoconazole on the PK of romidepsin; the PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Romidepsin Day 1 | Apparent Total Plasma Clearance (CL) | 16.922 L/hr | Geometric Coefficient of Variation 77.7 |
| Romidepsin and Ketoconazole Day 8 | Apparent Total Plasma Clearance (CL) | 14.84 L/hr | Geometric Coefficient of Variation 63 |
Primary
Apparent Total Volume of Distribution (Vz)
Vz: apparent total volume of distribution, calculated as \[(CL)/λz\].
Time frame: Days 1 and 8, At 0 (predose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion.
Population: Assess the influence of multiple doses of ketoconazole on the PK of romidepsin; the PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Romidepsin Day 1 | Apparent Total Volume of Distribution (Vz) | 236.4 Liter | Geometric Coefficient of Variation 88.7 |
| Romidepsin and Ketoconazole Day 8 | Apparent Total Volume of Distribution (Vz) | 217.78 Liter | Geometric Coefficient of Variation 80.5 |
Primary
Area Under the Plasma Concentration Time-curve From Time 0 Extrapolated to Infinity (AUC0-∞)
AUC0-∞: area under the plasma concentration time-curve from Time 0 extrapolated to infinity, calculated as \[AUCt + Ct/λz\].
Time frame: Days 1 and 8; at 0 (pre-dose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion.
Population: Assess the influence of multiple doses of ketoconazole on the PK of romidepsin. The PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Romidepsin Day 1 | Area Under the Plasma Concentration Time-curve From Time 0 Extrapolated to Infinity (AUC0-∞) | 915.3 ng*hr/mL | Geometric Coefficient of Variation 75.9 |
| Romidepsin and Ketoconazole Day 8 | Area Under the Plasma Concentration Time-curve From Time 0 Extrapolated to Infinity (AUC0-∞) | 1027.6 ng*hr/mL | Geometric Coefficient of Variation 59.3 |
90% CI: [109, 142.4]ANOVA
Primary
Area Under the Plasma Concentration Time-curve From Time 0 to 24-hour (AUC 0-24)
AUC 0-24: area under the plasma concentration time-curve from Time 0 to 24 hours, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing; for AUC 0-24 an analysis of variance (ANOVA) model was used to estimate the ratio of geometric means and its 90% confidence interval (CI) between romidepsin alone and romidepsin in the presence of ketoconazole
Time frame: Days 1 and 8; at 0 (predose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion
Population: Assess the influence of multiple doses of ketoconazole on the pharmacokinetic (PK) of romidepsin; the PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Romidepsin Day 1 | Area Under the Plasma Concentration Time-curve From Time 0 to 24-hour (AUC 0-24) | 900.1 ng*hr/mL | Geometric Coefficient of Variation 76.1 |
| Romidepsin and Ketoconazole Day 8 | Area Under the Plasma Concentration Time-curve From Time 0 to 24-hour (AUC 0-24) | 1002.2 ng*hr/mL | Geometric Coefficient of Variation 56.2 |
90% CI: [109.6, 139.6]ANOVA
Primary
Area Under the Plasma Concentration Time-curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t)of Romidepsin
AUC0-t: area under the plasma concentration time-curve from Time 0 to the time of the last quantifiable concentration (Ct), calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing. For AUC0-t, an analysis of variance (ANOVA) model was used to estimate the ratio of geometric means and its 90% CI between romidepsin alone and romidepsin in the presence to ketoconazole.
Time frame: Days 1 and 8; at 0 (pre-dose) 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion.
Population: Assessment on the influence of multiple doses of ketoconazole on the Pharmacokinetic (PK) of romidepsin; the PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Romidepsin Day 1 | Area Under the Plasma Concentration Time-curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t)of Romidepsin | 911.0 ng*hr/mL | Geometric Coefficient of Variation 76 |
| Romidepsin and Ketoconazole Day 8 | Area Under the Plasma Concentration Time-curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t)of Romidepsin | 1020.7 ng*hr/mL | Geometric Coefficient of Variation 56.4 |
90% CI: [110.2, 140.5]ANOVA
Primary
Estimate of the Terminal Elimination Half-life in Plasma (t1/2)
Terminal elimination half-life (t1/2) in plasma, was calculated as \[(ln 2)/λz\]
Time frame: Days 1 and 8; at 0 (pre-dose),1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion.
Population: Assess the influence of multiple doses of ketoconazole on the PK of romidepsin; the PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Romidepsin Day 1 | Estimate of the Terminal Elimination Half-life in Plasma (t1/2) | 9.69 hours | Geometric Coefficient of Variation 26.4 |
| Romidepsin and Ketoconazole Day 8 | Estimate of the Terminal Elimination Half-life in Plasma (t1/2) | 10.171 hours | Geometric Coefficient of Variation 15.5 |
Primary
Maximum Observed Plasma Concentration (Cmax)
Cmax: maximum observed plasma concentration, obtained directly from the observed concentration versus time data; for Cmax, an analysis of variance (ANOVA) model was used to estimate the ratio of geometric means and its 90% confidence interval (CI) between romidepsin alone and romidepsin in the presence of ketoconazole
Time frame: Days 1 and 8; at 0 (pre-dose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion.
Population: Assess the influence of multiple doses of ketoconazole on the PK of romidepsin. The PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Romidepsin Day 1 | Maximum Observed Plasma Concentration (Cmax) | 229.05 ng/mL | Geometric Coefficient of Variation 76.1 |
| Romidepsin and Ketoconazole Day 8 | Maximum Observed Plasma Concentration (Cmax) | 224.79 ng/mL | Geometric Coefficient of Variation 45.2 |
90% CI: [94.9, 126.4]ANOVA
Primary
Time to Maximum Observed Plasma Concentration (Tmax)
Tmax: time to maximum observed Tmax, obtained directly from the observed concentration versus time data
Time frame: Days 1 and 8; at 0 (pre-dose), 1, 2, 3, and 4 hours (end of infusion) and at 4.25, 4.5, 5, 6, 8, 10, 12, 24 and 48 hours after the initiation of IV infusion.
Population: Assess the influence of multiple doses of ketoconazole on the PK of romidepsin; the PK population included participants who received at least 1 dose of study drug and had evaluable PK profiles. The reasons for study discontinuation: 1 subject withdrew due to an AE while another subject had disease progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Romidepsin Day 1 | Time to Maximum Observed Plasma Concentration (Tmax) | 3.257 hours |
| Romidepsin and Ketoconazole Day 8 | Time to Maximum Observed Plasma Concentration (Tmax) | 2.992 hours |
Comparison: Note: The median, median difference (romidepsin + ketoconazole minus romidepsin) and 90% CI of the median difference are from Hodges-Lehmann Estimate. The P-value is from Wilcoxon signed-rank test.p-value: 0.742290% CI: [-0.485, 0.095]Wilcoxon signed- rank
Secondary
Summary of Participants With Treatment Emergent Adverse Events (TEAEs)
All 15 subjects in the safety population received at least 1 dose of romidepsin. AEs were considered related if assessed by the Investigator as possibly, probably or definitely related to study drug. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: Day 1 up to Day 36 (28 days after last treatment)
Population: The safety population consisted of all participants who received at least 1 dose of study drug. The Day 8 analysis population included 13 participants because two participants discontinued from the study prior to Day 8 (one due to an AE, the other due to disease progression).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 TEAE | 15 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 TEAE related to any study drug | 14 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 TEAE related to Romidepsin | 14 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 TEAE related to Ketoconazole | 4 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 Serious TEAE | 4 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 Serious TEAE related to any drug | 1 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 Serious TEAE related to Romidepsin | 1 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 Serious TEAE related to Ketoconazole | 0 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 TEAE leading to discontinuation | 1 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 TEAE related discontinuation due to any drug | 0 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 Romidepsin related TEAE discontinuation | 0 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | = > 1 Ketoconazole related TEAE discontinuation | 0 participants |
| Romidepsin Day 1 | Summary of Participants With Treatment Emergent Adverse Events (TEAEs) | Participants who died | 3 participants |