Trial Outcomes & Findings for 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 (NCT NCT01000376)
NCT ID: NCT01000376
Last Updated: 2013-09-23
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
7 days after dosing on Days 1 and 15
Results posted on
2013-09-23
Participant Flow
This study was conducted at 1 center in The Netherlands during the period of Feb 2009 to Jul 2009.
Participant milestones
| Measure |
Eribulin Alone First, Then Eribulin Plus Ketoconazole
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 Plus Ketoconazole First, Then Eribulin Alone
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.
|
|---|---|---|
|
Cycle 1 Day 1
STARTED
|
6
|
6
|
|
Cycle 1 Day 1
COMPLETED
|
4
|
6
|
|
Cycle 1 Day 1
NOT COMPLETED
|
2
|
0
|
|
Cycle 1 Day 15
STARTED
|
4
|
6
|
|
Cycle 1 Day 15
COMPLETED
|
4
|
6
|
|
Cycle 1 Day 15
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Eribulin Alone First, Then Eribulin Plus Ketoconazole
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 Plus Ketoconazole First, Then Eribulin Alone
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.
|
|---|---|---|
|
Cycle 1 Day 1
Adverse Event
|
1
|
0
|
|
Cycle 1 Day 1
Progressive Disease
|
1
|
0
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Eribulin Alone First, Then Eribulin Plus Ketoconazole
n=6 Participants
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 Plus Ketoconazole First, Then Eribulin Alone
n=6 Participants
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
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
58.3 years
STANDARD_DEVIATION 11.22 • n=5 Participants
|
62.5 years
STANDARD_DEVIATION 5.5 • n=7 Participants
|
60.4 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 7 days after dosing on Days 1 and 15Population: Pharmacokinetic Population: includes all participants in this crossover study who completed PK evaluations and who had Cmax data.
Outcome measures
| Measure |
Eribulin Alone
n=10 Participants
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 Plus Ketoconazole
n=10 Participants
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.
|
|---|---|---|
|
Mean (SD) Maximum Observed Concentration (Cmax) of Eribulin
|
207 ng*mL
Standard Deviation 73.9
|
106 ng*mL
Standard Deviation 33.7
|
PRIMARY outcome
Timeframe: 7 days after dosing on Days 1 and 15Population: Pharmacokinetic Population: includes all participants in this crossover study who completed PK evaluations and who had AUC (0-oo) data.
Outcome measures
| Measure |
Eribulin Alone
n=9 Participants
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 Plus Ketoconazole
n=7 Participants
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.
|
|---|---|---|
|
Mean (SD) Area Under Concentration Time Curve From Zero to Infinity (AUC 0-oo) of Eribulin
|
971 ng*hr/mL
Standard Deviation 371.9
|
482 ng*hr/mL
Standard Deviation 241.5
|
SECONDARY outcome
Timeframe: monitored throughoutOutcome measures
Outcome data not reported
Adverse Events
Eribulin Alone
Serious events: 4 serious events
Other events: 12 other events
Deaths: 0 deaths
Eribulin Plus Ketoconazole
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Eribulin Alone
n=12 participants at risk
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 Plus Ketoconazole
n=10 participants at risk
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.
|
|---|---|---|
|
General disorders
Pyrexia
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/12
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.
|
10.0%
1/10
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.
|
|
Gastrointestinal disorders
Ileus
|
8.3%
1/12
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.
|
0.00%
0/10
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.
|
|
Infections and infestations
Skin Infection
|
8.3%
1/12
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.
|
0.00%
0/10
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.
|
|
Metabolism and nutrition disorders
Anorexia
|
8.3%
1/12
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.
|
0.00%
0/10
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to CNS
|
8.3%
1/12
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.
|
0.00%
0/10
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.
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
8.3%
1/12
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.
|
0.00%
0/10
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.
|
Other adverse events
| Measure |
Eribulin Alone
n=12 participants at risk
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 Plus Ketoconazole
n=10 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
75.0%
9/12
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.
|
30.0%
3/10
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.
|
|
Gastrointestinal disorders
Constipation
|
41.7%
5/12
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.
|
20.0%
2/10
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.
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
4/12
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.
|
10.0%
1/10
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.
|
|
Gastrointestinal disorders
Stomatitis
|
33.3%
4/12
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.
|
10.0%
1/10
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.
|
|
Gastrointestinal disorders
Abdominal Pain
|
16.7%
2/12
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.
|
10.0%
1/10
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.
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
|
Gastrointestinal disorders
Dry Mouth
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
|
Gastrointestinal disorders
Dyspepsia
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
|
General disorders
Fatigue
|
83.3%
10/12
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.
|
30.0%
3/10
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.
|
|
General disorders
Edema Peripheral
|
33.3%
4/12
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.
|
10.0%
1/10
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.
|
|
General disorders
Pyrexia
|
25.0%
3/12
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.
|
10.0%
1/10
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.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
50.0%
6/12
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.
|
0.00%
0/10
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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
4/12
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.
|
0.00%
0/10
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.
|
|
Skin and subcutaneous tissue disorders
Night Sweats
|
16.7%
2/12
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.
|
10.0%
1/10
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.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
25.0%
3/12
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.
|
10.0%
1/10
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.
|
|
Skin and subcutaneous tissue disorders
Rhinorrhea
|
25.0%
3/12
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.
|
0.00%
0/10
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.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
|
Blood and lymphatic system disorders
Neutropenia
|
41.7%
5/12
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.
|
0.00%
0/10
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.
|
|
Blood and lymphatic system disorders
Anemia
|
16.7%
2/12
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.
|
10.0%
1/10
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.
|
|
Investigations
Weight Decreased
|
33.3%
4/12
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.
|
0.00%
0/10
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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
|
Nervous system disorders
Headache
|
16.7%
2/12
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.
|
10.0%
1/10
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.
|
|
Nervous system disorders
Dizziness
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
|
Eye disorders
Lacrimation Increased
|
33.3%
4/12
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.
|
10.0%
1/10
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.
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
4/12
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.
|
0.00%
0/10
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.
|
|
Infections and infestations
Herpes Simplex
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
|
Psychiatric disorders
Confusional State
|
8.3%
1/12
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.
|
0.00%
0/10
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.
|
|
Psychiatric disorders
Insomnia
|
16.7%
2/12
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.
|
0.00%
0/10
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.
|
Additional Information
Dr. Peter Tarassoff
Eisai
Phone: 888-422-4743
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place