Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Hematologic Neoplasms

Hematologic Diseases

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Ketoconazole

Romidepsin

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Histone Deacetylase Inhibitors

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

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

Ken Takeshita, MD

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.

Influence of Ketoconazole on the Pharmacokinetics of Romidepsin in Patients With Advanced Cancer

A Phase I Open-label, 2-period Study to Evaluate the Influence of Multiple Oral Doses of Ketoconazole on the Single Dose Pharmacokinetics of Romidepsin in Subjects With Advanced Cancer

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.

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

AUC0-∞: area under the plasma concentration time-curve from Time 0 extrapolated to infinity, calculated as \[AUCt + Ct/λz\].

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

Tmax: time to maximum observed Tmax, obtained directly from the observed concentration versus time data

Terminal elimination half-life (t1/2) in plasma, was calculated as \[(ln 2)/λz\]

Apparent total plasma clearance, (CL) calculated as \[Dose/AUC 0-∞\].

Vz: apparent total volume of distribution, calculated as \[(CL)/λz\].

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.

Celgene

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

Romidepsin Plus Ketoconazole

Romidepsin and Ketoconazole

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Asian

Black or African American

Other

Race/Ethnicity, Customized

United Kingdom

United States

Region of Enrollment

Height

Weight

Body Surface Area (BSA)

0 = Fully Active

1 = Restricted in physical strenuous activity

2 = Ambulatory but unable to work

3 = Limited Self Care

4 = Completely Disabled

Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living activities of the patient and determine appropriate treatment and prognosis.

0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care

Eastern Cooperative Oncology Group Performance Status (ECOG)

Senior Manager

Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 1

Romidepsin Day 1

Romidepsin 8 mg/m\^2 intravenous infused over 4 hours on Day 8; Ketoconazole 400 mg oral once daily on Days 4-8

Romidepsin and Ketoconazole Day 8

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.

Area Under the Plasma Concentration Time-curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t)of Romidepsin

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.

Area Under the Plasma Concentration Time-curve From Time 0 to 24-hour (AUC 0-24)

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.

Area Under the Plasma Concentration Time-curve From Time 0 Extrapolated to Infinity (AUC0-∞)

Maximum Observed Plasma Concentration (Cmax)

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.

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.

Time to Maximum Observed Plasma Concentration (Tmax)

Estimate of the Terminal Elimination Half-life in Plasma (t1/2)

Apparent Total Plasma Clearance (CL)

Apparent Total Volume of Distribution (Vz)

= > 1 TEAE

= > 1 TEAE related to any study drug

= > 1 TEAE related to Romidepsin

= > 1 TEAE related to Ketoconazole

= > 1 Serious TEAE

= > 1 Serious TEAE related to any drug

= > 1 Serious TEAE related to Romidepsin

= > 1 Serious TEAE related to Ketoconazole

= > 1 TEAE leading to discontinuation

= > 1 TEAE related discontinuation due to any drug

= > 1 Romidepsin related TEAE discontinuation

= > 1 Ketoconazole related TEAE discontinuation

Participants who died

Romidepsin 8 mg/m2 intravenous infused over 4 hours on Day 1 and Day 8. Ketoconazole 400 mg oral once daily on Days 4-8

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).

Summary of Participants With Treatment Emergent Adverse Events (TEAEs)

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

Spots Global Cancer Trial Database for Influence of Ketoconazole on the Pharmacokinetics of Romidepsin in Patients With Advanced Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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