Trial Outcomes & Findings for QT Interval Prolongation Study of Eribulin Mesylate (E7389) in Patients With Advanced Solid Tumors (NCT NCT01106248)
NCT ID: NCT01106248
Last Updated: 2012-04-13
Results Overview
The primary endpoint is mean time-matched, baseline corrected QTcF at any time point postdosing. This was to determine the effect of eribulin on cardiac repolarization as measured by QT/QTc interval.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
48 hours postdose after Day 1 and after Day 8
Results posted on
2012-04-13
Participant Flow
This study was recruited at 5 centers in France from Feb 2009 to Jul 2009.
Participant milestones
| Measure |
Eribulin Mesylate
1.4 mg/m\^2 intravenous (IV) bolus given over 2-5 minutes on Days 1 and 8 every 21 days.
|
|---|---|
|
Overall Study
STARTED
|
26
|
|
Overall Study
COMPLETED
|
23
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Eribulin Mesylate
1.4 mg/m\^2 intravenous (IV) bolus given over 2-5 minutes on Days 1 and 8 every 21 days.
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Administrative
|
2
|
Baseline Characteristics
QT Interval Prolongation Study of Eribulin Mesylate (E7389) in Patients With Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
Eribulin Mesylate
n=26 Participants
1.4 mg/m\^2 intravenous (IV) bolus given over 2-5 minutes on Days 1 and 8 every 21 days.
|
|---|---|
|
Age Continuous
|
55.9 years
STANDARD_DEVIATION 12.28 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
26 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 hours postdose after Day 1 and after Day 8Population: Per Protocol Population
The primary endpoint is mean time-matched, baseline corrected QTcF at any time point postdosing. This was to determine the effect of eribulin on cardiac repolarization as measured by QT/QTc interval.
Outcome measures
| Measure |
Eribulin Mesylate
n=26 Participants
1.4 mg/m\^2 intravenous (IV) bolus given over 2-5 minutes on Days 1 and 8 every 21 days.
|
|---|---|
|
Mean Time-matched, Baseline Corrected QTcF at Any Time Point Postdosing.
Postdosing Day 1
|
2 msec
Standard Deviation 12.3
|
|
Mean Time-matched, Baseline Corrected QTcF at Any Time Point Postdosing.
Postdosing Day 8
|
11 msec
Standard Deviation 18.7
|
SECONDARY outcome
Timeframe: Days 1 and 8Population: Pharmacokinetic Population
Pharmacokinetic profile of eribulin mesylate (Cmax).
Outcome measures
| Measure |
Eribulin Mesylate
n=26 Participants
1.4 mg/m\^2 intravenous (IV) bolus given over 2-5 minutes on Days 1 and 8 every 21 days.
|
|---|---|
|
Pharmacokinetic Profile of Eribulin Mesylate: Observed Maximal Plasma Concentration (Cmax)
Day 1
|
516.5 ng/mL
Standard Deviation 137.91
|
|
Pharmacokinetic Profile of Eribulin Mesylate: Observed Maximal Plasma Concentration (Cmax)
Day 8
|
502.4 ng/mL
Standard Deviation 138.31
|
SECONDARY outcome
Timeframe: 21 day cycleOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 21 day cycleOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 1 and 8Population: Pharmacokinetic Population
Pharmacokinetic profile of eribulin mesylate (tmax).
Outcome measures
| Measure |
Eribulin Mesylate
n=26 Participants
1.4 mg/m\^2 intravenous (IV) bolus given over 2-5 minutes on Days 1 and 8 every 21 days.
|
|---|---|
|
Pharmacokinetic Profile of Eribulin Mesylate: Time to Maximum Observed Plasma Concentration (Tmax).
Day 1
|
0.08 hours
Interval 0.07 to 0.25
|
|
Pharmacokinetic Profile of Eribulin Mesylate: Time to Maximum Observed Plasma Concentration (Tmax).
Day 8
|
0.08 hours
Interval 0.05 to 0.25
|
Adverse Events
Eribulin Mesylate
Serious events: 11 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Eribulin Mesylate
n=26 participants at risk
1.4 mg/m\^2 intravenous (IV) bolus given over 2-5 minutes on Days 1 and 8 every 21 days.
|
|---|---|
|
General disorders
General Physical Health Deterioration
|
19.2%
5/26
|
|
General disorders
Pyrexia
|
11.5%
3/26
|
|
General disorders
Asthenia
|
7.7%
2/26
|
|
General disorders
Non-Cardiac Chest Pain
|
3.8%
1/26
|
|
Gastrointestinal disorders
Vomting
|
7.7%
2/26
|
|
Gastrointestinal disorders
Subileus
|
3.8%
1/26
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
11.5%
3/26
|
|
Infections and infestations
Bacteremia
|
3.8%
1/26
|
|
Infections and infestations
Mastoiditis
|
3.8%
1/26
|
|
Nervous system disorders
Headache
|
3.8%
1/26
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
3.8%
1/26
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
3.8%
1/26
|
|
Renal and urinary disorders
Renal Failure
|
3.8%
1/26
|
|
Renal and urinary disorders
Urinary Retention
|
3.8%
1/26
|
|
Blood and lymphatic system disorders
Anemia
|
3.8%
1/26
|
|
Eye disorders
Diplopia
|
3.8%
1/26
|
|
Hepatobiliary disorders
Hepatitis
|
3.8%
1/26
|
|
Investigations
Weight Decreased
|
3.8%
1/26
|
|
Metabolism and nutrition disorders
Anorexia
|
3.8%
1/26
|
|
Psychiatric disorders
Depression
|
3.8%
1/26
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.8%
1/26
|
Other adverse events
| Measure |
Eribulin Mesylate
n=26 participants at risk
1.4 mg/m\^2 intravenous (IV) bolus given over 2-5 minutes on Days 1 and 8 every 21 days.
|
|---|---|
|
Gastrointestinal disorders
Constipation
|
61.5%
16/26
|
|
Gastrointestinal disorders
Nausea
|
46.2%
12/26
|
|
Gastrointestinal disorders
Vomiting
|
42.3%
11/26
|
|
Gastrointestinal disorders
Diarrhea
|
34.6%
9/26
|
|
Gastrointestinal disorders
Abdominal Pain
|
11.5%
3/26
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
7.7%
2/26
|
|
Gastrointestinal disorders
Stomatitis
|
7.7%
2/26
|
|
Gastrointestinal disorders
Bezoar
|
3.8%
1/26
|
|
Gastrointestinal disorders
Dry Mouth
|
3.8%
1/26
|
|
Gastrointestinal disorders
Dysphagia
|
3.8%
1/26
|
|
Gastrointestinal disorders
Fecal Incontinence
|
3.8%
1/26
|
|
Gastrointestinal disorders
Gastroesophageal Reflux Disease
|
3.8%
1/26
|
|
Gastrointestinal disorders
Esophageal Pain
|
3.8%
1/26
|
|
Gastrointestinal disorders
Subileus
|
3.8%
1/26
|
|
Gastrointestinal disorders
Toothache
|
3.8%
1/26
|
|
General disorders
Asthenia
|
53.8%
14/26
|
|
General disorders
Pyrexia
|
34.6%
9/26
|
|
General disorders
Fatigue
|
19.2%
5/26
|
|
General disorders
General Physical Health Deterioration
|
19.2%
5/26
|
|
General disorders
Peripheral Edema
|
15.4%
4/26
|
|
General disorders
Mucosal Inflammation
|
7.7%
2/26
|
|
General disorders
Chills
|
3.8%
1/26
|
|
General disorders
Malaise
|
3.8%
1/26
|
|
General disorders
Non-Cardiac Chest Pain
|
3.8%
1/26
|
|
Blood and lymphatic system disorders
Neutropenia
|
61.5%
16/26
|
|
Blood and lymphatic system disorders
Anemia
|
46.2%
12/26
|
|
Blood and lymphatic system disorders
Leukopenia
|
38.5%
10/26
|
|
Blood and lymphatic system disorders
Lymphopenia
|
23.1%
6/26
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.8%
1/26
|
|
Blood and lymphatic system disorders
Paratracheal Lymphadenopathy
|
3.8%
1/26
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
19.2%
5/26
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
19.2%
5/26
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
15.4%
4/26
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.7%
2/26
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
7.7%
2/26
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
7.7%
2/26
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
7.7%
2/26
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
3.8%
1/26
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
|
3.8%
1/26
|
|
Nervous system disorders
Headache
|
23.1%
6/26
|
|
Nervous system disorders
Dysgeusia
|
11.5%
3/26
|
|
Nervous system disorders
Parasthesia
|
11.5%
3/26
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
7.7%
2/26
|
|
Nervous system disorders
Presyncope
|
7.7%
2/26
|
|
Nervous system disorders
Dizziness
|
3.8%
1/26
|
|
Nervous system disorders
Intracranial Pressure Increased
|
3.8%
1/26
|
|
Nervous system disorders
Neuralgia
|
3.8%
1/26
|
|
Nervous system disorders
Paraparesis
|
3.8%
1/26
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
3.8%
1/26
|
|
Nervous system disorders
Tongue Paralysis
|
3.8%
1/26
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
42.3%
11/26
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
3.8%
1/26
|
|
Skin and subcutaneous tissue disorders
Dermatitis Contact
|
3.8%
1/26
|
|
Skin and subcutaneous tissue disorders
Erythema
|
3.8%
1/26
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
3.8%
1/26
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.8%
1/26
|
|
Infections and infestations
Oral Herpes
|
7.7%
2/26
|
|
Infections and infestations
Urinary Tract Infection
|
7.7%
2/26
|
|
Infections and infestations
Bacteremia
|
3.8%
1/26
|
|
Infections and infestations
Bronchitis
|
3.8%
1/26
|
|
Infections and infestations
Catheter Related Infection
|
3.8%
1/26
|
|
Infections and infestations
Fungal Skin Infection
|
3.8%
1/26
|
|
Infections and infestations
Mastoiditis
|
3.8%
1/26
|
|
Infections and infestations
Sinusitis
|
3.8%
1/26
|
|
Infections and infestations
Tracheitis
|
3.8%
1/26
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.4%
4/26
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
15.4%
4/26
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
7.7%
2/26
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
7.7%
2/26
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.8%
1/26
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
3.8%
1/26
|
|
Investigations
Alanine Aminotransferase Increased
|
11.5%
3/26
|
|
Investigations
Aspartate Aminotransferase Increased
|
11.5%
3/26
|
|
Investigations
Weight Decreased
|
11.5%
3/26
|
|
Investigations
Gamma Glutamyltransferase Increased
|
7.7%
2/26
|
|
Investigations
Alanine Aminotransferase Decreased
|
3.8%
1/26
|
|
Investigations
Blood Alkaline Phosphatase Increased
|
3.8%
1/26
|
|
Investigations
Blood Bilirubin Increased
|
3.8%
1/26
|
|
Investigations
Gamma Glutamyltransferase Decreased
|
3.8%
1/26
|
|
Investigations
Weight Increased
|
3.8%
1/26
|
|
Psychiatric disorders
Insomnia
|
15.4%
4/26
|
|
Psychiatric disorders
Anxiety
|
7.7%
2/26
|
|
Psychiatric disorders
Confusional State
|
7.7%
2/26
|
|
Psychiatric disorders
Agitation
|
3.8%
1/26
|
|
Psychiatric disorders
Depression
|
3.8%
1/26
|
|
Renal and urinary disorders
Urinary Retention
|
7.7%
2/26
|
|
Renal and urinary disorders
Hematuria
|
3.8%
1/26
|
|
Renal and urinary disorders
Renal Failure
|
3.8%
1/26
|
|
Renal and urinary disorders
Urinary Incontinence
|
3.8%
1/26
|
|
Cardiac disorders
Atrial Fibrillation
|
7.7%
2/26
|
|
Cardiac disorders
Tachycardia
|
3.8%
1/26
|
|
Ear and labyrinth disorders
Deafness
|
3.8%
1/26
|
|
Ear and labyrinth disorders
Tinnitis
|
3.8%
1/26
|
|
Ear and labyrinth disorders
Vertigo
|
3.8%
1/26
|
|
Hepatobiliary disorders
Hepatic Pain
|
7.7%
2/26
|
|
Hepatobiliary disorders
Cholestasis
|
3.8%
1/26
|
|
Hepatobiliary disorders
Hepatitis
|
3.8%
1/26
|
|
Eye disorders
Conjunctivitis
|
3.8%
1/26
|
|
Eye disorders
Diplopia
|
3.8%
1/26
|
|
Vascular disorders
Hypotension
|
3.8%
1/26
|
|
Vascular disorders
Lymphoedema
|
3.8%
1/26
|
Additional Information
Dr. Peter Tarassoff
Eisai
Phone: 888-422-4743
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place