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Evaluating the Pharmacokinetics and Tolerance of Co-administration of Oral Multiple Dose of Ketoconazole and an IV (Bolus) Infusion of Eribulin in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT01000376
Recruitment Status : Completed
First Posted : October 23, 2009
Results First Posted : September 23, 2013
Last Update Posted : September 23, 2013
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Limited )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cancer
Interventions Drug: Eribulin alone
Drug: Eribulin plus Ketoconazole
Enrollment 12
Recruitment Details This study was conducted at 1 center in The Netherlands during the period of Feb 2009 to Jul 2009.
Pre-assignment Details  
Arm/Group Title Eribulin Alone First, Then Eribulin Plus Ketoconazole Eribulin Plus Ketoconazole First, Then Eribulin Alone
Hide Arm/Group Description Eribulin IV 1.4 mg/m^2 alone on Day 1, then eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 15 and oral ketoconazole 200 mg alone on Day 16 of a 28 day cycle. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days. Eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 1, then oral ketoconazole 200 mg alone on Day 2 and eribulin IV 1.4 mg/m^2 alone on Day 15 of a 28 day cycle. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days.
Period Title: Cycle 1 Day 1
Started 6 6
Completed 4 6
Not Completed 2 0
Reason Not Completed
Adverse Event             1             0
Progressive Disease             1             0
Period Title: Cycle 1 Day 15
Started 4 6
Completed 4 6
Not Completed 0 0
Arm/Group Title Eribulin Alone First, Then Eribulin Plus Ketoconazole Eribulin Plus Ketoconazole First, Then Eribulin Alone Total
Hide Arm/Group Description Eribulin IV 1.4 mg/m^2 alone on Day 1, then eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 15 and oral ketoconazole 200 mg alone on Day 16 of a 28 day cycle. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days. Eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 1, then oral ketoconazole 200 mg alone on Day 2 and eribulin IV 1.4 mg/m^2 alone on Day 15 of a 28 day cycle. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days. Total of all reporting groups
Overall Number of Baseline Participants 6 6 12
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 12 participants
58.3  (11.22) 62.5  (5.5) 60.4  (8.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
Female
3
  50.0%
1
  16.7%
4
  33.3%
Male
3
  50.0%
5
  83.3%
8
  66.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
6
 100.0%
6
 100.0%
12
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Netherlands Number Analyzed 6 participants 6 participants 12 participants
6 6 12
1.Primary Outcome
Title Mean (SD) Maximum Observed Concentration (Cmax) of Eribulin
Hide Description [Not Specified]
Time Frame 7 days after dosing on Days 1 and 15
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population: includes all participants in this crossover study who completed PK evaluations and who had Cmax data.
Arm/Group Title Eribulin Alone Eribulin Plus Ketoconazole
Hide Arm/Group Description:
Eribulin IV 1.4 mg/m^2 alone on Day 1, then eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 15 and oral ketoconazole 200 mg alone on Day 16 of a 28 day cycle. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days.
Eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 1, then oral ketoconazole 200 mg alone on Day 2 and eribulin IV 1.4 mg/m^2 alone on Day 15 of a 28 day cycle. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days.
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: ng*mL
207  (73.9) 106  (33.7)
2.Primary Outcome
Title Mean (SD) Area Under Concentration Time Curve From Zero to Infinity (AUC 0-oo) of Eribulin
Hide Description [Not Specified]
Time Frame 7 days after dosing on Days 1 and 15
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Population: includes all participants in this crossover study who completed PK evaluations and who had AUC (0-oo) data.
Arm/Group Title Eribulin Alone Eribulin Plus Ketoconazole
Hide Arm/Group Description:
Eribulin IV 1.4 mg/m^2 alone on Day 1, then eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 15 and oral ketoconazole 200 mg alone on Day 16 of a 28 day cycle. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days.
Eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 1, then oral ketoconazole 200 mg alone on Day 2 and eribulin IV 1.4 mg/m^2 alone on Day 15 of a 28 day cycle. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days.
Overall Number of Participants Analyzed 9 7
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
971  (371.9) 482  (241.5)
3.Secondary Outcome
Title Safety of Eribulin Administered Alone or Coadministered With Oral Ketoconazole, as Measured by Number of Subjects With Adverse Events.
Hide Description [Not Specified]
Time Frame monitored throughout
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description Number of participants at risk reflects the Safety Population which included all participants enrolled in this crossover study and received at least a partial dose of study treatment.
 
Arm/Group Title Eribulin Alone Eribulin Plus Ketoconazole
Hide Arm/Group Description Eribulin IV 1.4 mg/m^2 alone on Day 1, then eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 15 and oral ketoconazole 200 mg alone on Day 16 of a 28 day cycle. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days. Eribulin IV 0.7 mg/m^2 plus oral ketoconazole 200 mg on Day 1, then oral ketoconazole 200 mg alone on Day 2 and eribulin IV 1.4 mg/m^2 alone on Day 15 of a 28 day cycle. Subsequently, subjects were able to receive eribulin 1.4 mg/m^2 on Days 1 and 8 every 21 days.
All-Cause Mortality
Eribulin Alone Eribulin Plus Ketoconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Eribulin Alone Eribulin Plus Ketoconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   4/12 (33.33%)   1/10 (10.00%) 
Blood and lymphatic system disorders     
Anemia  0/12 (0.00%)  1/10 (10.00%) 
Gastrointestinal disorders     
Ileus  1/12 (8.33%)  0/10 (0.00%) 
General disorders     
Pyrexia  2/12 (16.67%)  0/10 (0.00%) 
Infections and infestations     
Skin Infection  1/12 (8.33%)  0/10 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  1/12 (8.33%)  0/10 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastases to CNS  1/12 (8.33%)  0/10 (0.00%) 
Nervous system disorders     
Peripheral Motor Neuropathy  1/12 (8.33%)  0/10 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Eribulin Alone Eribulin Plus Ketoconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   12/12 (100.00%)   8/10 (80.00%) 
Blood and lymphatic system disorders     
Neutropenia  5/12 (41.67%)  0/10 (0.00%) 
Anemia  2/12 (16.67%)  1/10 (10.00%) 
Eye disorders     
Lacrimation Increased  4/12 (33.33%)  1/10 (10.00%) 
Gastrointestinal disorders     
Nausea  9/12 (75.00%)  3/10 (30.00%) 
Constipation  5/12 (41.67%)  2/10 (20.00%) 
Vomiting  4/12 (33.33%)  1/10 (10.00%) 
Stomatitis  4/12 (33.33%)  1/10 (10.00%) 
Abdominal Pain  2/12 (16.67%)  1/10 (10.00%) 
Abdominal Pain Upper  2/12 (16.67%)  0/10 (0.00%) 
Dry Mouth  2/12 (16.67%)  0/10 (0.00%) 
Dyspepsia  2/12 (16.67%)  0/10 (0.00%) 
General disorders     
Fatigue  10/12 (83.33%)  3/10 (30.00%) 
Edema Peripheral  4/12 (33.33%)  1/10 (10.00%) 
Pyrexia  3/12 (25.00%)  1/10 (10.00%) 
Infections and infestations     
Herpes Simplex  2/12 (16.67%)  0/10 (0.00%) 
Investigations     
Weight Decreased  4/12 (33.33%)  0/10 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  4/12 (33.33%)  0/10 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  2/12 (16.67%)  0/10 (0.00%) 
Myalgia  2/12 (16.67%)  0/10 (0.00%) 
Nervous system disorders     
Headache  2/12 (16.67%)  1/10 (10.00%) 
Dizziness  2/12 (16.67%)  0/10 (0.00%) 
Peripheral Motor Neuropathy  2/12 (16.67%)  0/10 (0.00%) 
Psychiatric disorders     
Confusional State  1/12 (8.33%)  0/10 (0.00%) 
Insomnia  2/12 (16.67%)  0/10 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea  3/12 (25.00%)  1/10 (10.00%) 
Epistaxis  2/12 (16.67%)  0/10 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia  6/12 (50.00%)  0/10 (0.00%) 
Rash  4/12 (33.33%)  0/10 (0.00%) 
Night Sweats  2/12 (16.67%)  1/10 (10.00%) 
Rhinorrhea  3/12 (25.00%)  0/10 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Peter Tarassoff
Organization: Eisai
Phone: 888-422-4743
Layout table for additonal information
Responsible Party: Eisai Inc. ( Eisai Limited )
ClinicalTrials.gov Identifier: NCT01000376    
Other Study ID Numbers: E7389-E044-109
First Submitted: October 22, 2009
First Posted: October 23, 2009
Results First Submitted: December 22, 2011
Results First Posted: September 23, 2013
Last Update Posted: September 23, 2013