An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820 to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors
Sponsor
Eisai Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01773421
Collaborator
(none)
45
6
2
76.5
7.5
0.1
Study Details
Study Description
Brief Summary
This study consists of two Parts. Part A (Food Effect Study) and Part B (Determination of Maximum Tolerated Dose [MTD] for twice daily [BID] Dosing).Part A will be initiated first, and Part B will be initiated after the PK results of Part A have been evaluated.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
45 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820, to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors
Actual Study Start Date
:
Jun 30, 2011
Actual Primary Completion Date
:
Apr 30, 2014
Actual Study Completion Date
:
Nov 12, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A
|
Drug: E7820
FOOD EFFECT STUDY:
Each subject (a minimum of 12 subjects) will be assigned according to a randomization code to receive a single 50 mg dose of E7820 on Day 1, either after fasting for 10 hours, or immediately after consuming a high fat breakfast. Following a 7-day washout period, the subjects will crossover and a second 50 mg dose of E7820 will be administered on Day 8.
|
| Experimental: Part B
|
Drug: E7820
MTD DETERMINATION FOR BID DOSING SCHEDULE
The initial dose of E7820 will be 50 mg BID. If allowed by the rules for dose escalation, the dose escalations will be to 60 mg BID, 80 mg BID, and 100 mg BID.
|
Outcome Measures
Primary Outcome Measures
- Treatment Phase Part A: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for E7820 [Day 1 or 8: 0.5-48 hours]
- Treatment Phase Part A: AUC(0-t): Area Under the Plasma Concentration- Time Curve From Time 0 to t for E7820 [Day 1 or 8: 0.5-48 hours]
- Treatment Phase Part A: Cmax: Maximum Observed Plasma Concentration for E7820 [Day 1 or 8: 0.5-48 hours]
- Treatment Phase Part B: Maximum Tolerated Dose (MTD) of E7820 BID Dosing Schedule [Up to Cycle 6 (Cycle length =28 days)]
MTD defined as the highest dose level at which no more than 1 of 6 participants experienced a dose-limiting toxicity(DLT), with the next higher dose having at least 2 of 3 or 2 of 6 participants experiencing DLTs. DLTs were defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events(CTCAE) Version 4.03 as: Neutropenia less than(<) 0.5*10^9/liter(L) for greater than(>) 5 days; neutropenia <1*10^9/L with fever; thrombocytopenia <25*10^9/L accompanied by bleeding or thrombocytopenia <10*10^9/L; any Grade 3 or 4 nonhematological toxicity for which the study drug could not be excluded as a cause (other than nausea, vomiting or diarrhea in the absence of appropriate prophylaxis) with the following clarification: Grade 3 or 4 nonhematological laboratory abnormalities for which there was no expected clinical correlation would not be considered DLTs; treatment delay of >14 days required to recover from E7820-related toxicities.
Secondary Outcome Measures
- Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) [From first dose of study drug (Baseline) up to approximately 6.6 years]
BOR based on RECIST 1.1 for target and non-target lesions is complete response (CR) or partial response (PR) for >4 weeks or stable disease (SD) for >5 weeks from first dose. CR: disappearance of target and non-target lesions, normalization of tumor marker level, all lymph nodes must be non- pathological in size (<10 millimeter [mm] short axis). PR: at least 30% decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
- Extension Phase Part A, and Treatment and Extension Phase Part B: Duration of Response [From date of first documented confirmed CR/PR until date of first documentation of PD or death (approximately up to 6.6 years)]
Duration of response based on RECIST 1.1 for target and non-target lesions is the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever came first. CR: disappearance of target and non-target lesions,normalization of tumor marker level,all lymph nodes must be non-pathological in size(<10 mm short axis). PR: at least 30% decrease in SOD of target lesions,taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD:at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions,taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
- Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) [From first dose date to the date of the first documentation of confirmed PD or death (approximately up to 6.6 years)]
PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions. For PD: participants with best response of PD have been reported. For Death: participants with death known to have died at any point have been reported.
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)]
Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; physical examinations; and regular measurement of vital signs, ECG, and multiple-gated acquisition (MUGA) scans or echocardiograms.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age 18 years or older.
-
Histological or cytological evidence of an unresectable or refractory solid tumor.
-
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
-
Subjects with known brain metastases will be eligible under the following conditions
- Have undergone complete surgical excision and are more then 1 month post surgery with no radiographic evidence of brain disease recurrence or B. Have undergone stereotactic radio surgery (gamma knife procedure) and are more then 1 month post procedure and with no radiographic evidence of brain disease progression and C. Are asymptomatic and D. Discontinued corticosteroid treatment at least 30 days prior to Cycle 1, Day 1
-
Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN (in the case of liver metastases less than or equal to 5 x ULN) In case alkaline phosphatase is greater than 3 x ULN (in absence of liver metastases) or greater than 5 x ULN (in presence of liver metastases) AND subject also is known to have bone metastases, the liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase.
-
Adequate renal function as evidenced by serum creatinine less than or equal to 2.0 mg/dL (177 micro-mol/L) or calculated creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula
-
Provide written informed consent.
-
Are willing and able to comply with all aspects of the protocol.
-
Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, hemoglobin greater than or equal to 9 g/dL (5.5 mmol/L) and platelet count greater than or equal to 100 x 109/L.
-
Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [beta-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
-
All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
-
Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
-
Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.
Exclusion Criteria:
-
Leptomeningeal metastases or brain metastases (except as for inclusion criteria #4).
-
Active hemoptysis (at least 2.5 mL [0.5 teaspoon] bright red blood) within 3 weeks prior to the first dose of study drug.
-
Hypersensitivity to sulfonamide derivatives.
-
Subjects who have had radiation to greater than or equal to 30% of their bone marrow.
-
Subjects who require therapeutic anti-coagulant therapy with warfarin or related vitamin K antagonists. Prophylactic doses of heparin or low molecular weight heparin or thrombin inhibitors may be used in place of warfarin.
-
Left ventricular ejection fraction less than 50% on echocardiography or MUGA scanning.
-
Anticancer therapies that have not been completed at least 28 days (42 days in the case of mitomycin C or nitrosoureas) prior to treatment with E7820 (other than surgery or treatment with a protein kinase inhibitor which must have been completed no less than one week prior to treatment with E7820).
-
Incomplete recovery from previous radiotherapy, chemotherapy, or surgery other than residual cutaneous effects or stable less than Grade 2 gastrointestinal toxicity.
-
History of an ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months before study entry.
-
A clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolongation of QTc interval greater than 480 msec.
-
Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject's safety or study conduct.
-
Concurrent treatment with CYP3A4 inhibitors such as verapamil, cyclosporin, quinidine, erythromycin, mibefradil, clarithramycin and azoles.
-
Concurrent treatment with drugs known to be extensively metabolized by CYP2C9 and/or CYP2C19.
-
Chronic treatment with known inducers of CYP3A4 within four weeks of receiving treatment with E7820 other than corticosteroids (Appendix 6).
-
Subjects who have a positive test result for human immunodeficiency virus (HIV), hepatitis A, hepatitis B or hepatitis C.
-
Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years.
-
History of drug or alcohol dependency or abuse within approximately the last 2 years.
-
Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
-
Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
-
Use of illegal recreational drugs.
-
Any medical or other condition that, in the opinion of the investigator, would preclude the subject's participation in a study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Netherlands Cancer Institute | Amsterdam | Netherlands | ||
| 2 | University Medical Centre Utrecht | Utrecht | Netherlands | ||
| 3 | Beatson West of Scotland Cancer Centre | Glasgow | United Kingdom | ||
| 4 | University College London Hospital | London | United Kingdom | ||
| 5 | The Christie Hospital | Manchester | United Kingdom | ||
| 6 | Sir Bobby Robson Cancer Trials Research Centre | Newcastle | United Kingdom |
Sponsors and Collaborators
- Eisai Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01773421
Other Study ID Numbers:
- E7820-E044-110
- 2010-023655-28
First Posted:
Jan 23, 2013
Last Update Posted:
Jan 18, 2020
Last Verified:
Feb 1, 2018
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 6 investigative sites in the Netherlands and United Kingdom from 30 June 2011 to 12 November 2017. |
|---|---|
| Pre-assignment Detail | In Part A, a total of 18 participants were enrolled, out of which 15 participants were randomized and treated. In Part B, a total of 27 participants were enrolled, out of which 26 participants were treated. |
| Arm/Group Title | Treatment Phase Part A: E7820 50 mg Fed+ E7820 50 mg Fasted | Treatment Phase Part A: E7820 50 mg Fasted + E7820 50 mg Fed | Treatment Phase Part B: E7820 50 mg | Treatment Phase Part B: E7820 60 mg | Extension Phase Part A: E7820 100 mg | Extension Phase Part B: E7820 50 mg | Extension Phase Part B: E7820 60 mg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received E7820 50 milligram (mg), tablet, orally, under fed condition on Day 1, followed by E7820 50 mg, tablet, orally, under fasted condition on Day 8. A washout period of 7 days was maintained between the doses. | Participants received E7820 50 mg, tablet, orally, under fasted condition on Day 1, followed by E7820 50 mg, tablet, orally, under fed condition on Day 8. A washout period of 7 days was maintained between the doses. | Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. | Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. | Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 100 mg, once daily, tablet, orally, under fasted condition, during 28-day cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. No participants from the treatment phase Part B: E7820 60 mg entered the extension phase. |
| Period Title: Treatment Phase | |||||||
| STARTED | 7 | 8 | 19 | 7 | 0 | 0 | 0 |
| COMPLETED | 7 | 8 | 13 | 5 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 6 | 2 | 0 | 0 | 0 |
| Period Title: Treatment Phase | |||||||
| STARTED | 0 | 0 | 0 | 0 | 15 | 3 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 12 | 1 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 3 | 2 | 0 |
Baseline Characteristics
| Arm/Group Title | Treatment Phase Part A: E7820 50 mg Fed+ E7820 50 mg Fasted | Treatment Phase Part A: E7820 50 mg Fasted + E7820 50 mg Fed | Treatment Phase Part B: E7820 50 mg | Treatment Phase Part B: E7820 60 mg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received E7820 50 mg, tablet, orally, under fed condition on Day 1, followed by E7820 50 mg, tablet, orally, under fasted condition on Day 8. A washout period of 7 days was maintained between the doses. | Participants received E7820 50 mg, tablet, orally, under fasted condition on Day 1, followed by E7820 50 mg, tablet, orally, under fed condition on Day 8. A washout period of 7 days was maintained between the doses. | Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. | Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. | Total of all reporting groups |
| Overall Participants | 7 | 8 | 19 | 7 | 41 |
| Age, Customized (Count of Participants) | |||||
| Between 18 and 44 years |
0
0%
|
2
25%
|
1
5.3%
|
1
14.3%
|
4
9.8%
|
| Between 45 and 64 years |
5
71.4%
|
1
12.5%
|
8
42.1%
|
5
71.4%
|
19
46.3%
|
| Between 65 and 74 years |
1
14.3%
|
3
37.5%
|
9
47.4%
|
1
14.3%
|
14
34.1%
|
| Greater than (>) 74 years |
1
14.3%
|
2
25%
|
1
5.3%
|
0
0%
|
4
9.8%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
4
57.1%
|
3
37.5%
|
6
31.6%
|
2
28.6%
|
15
36.6%
|
| Male |
3
42.9%
|
5
62.5%
|
13
68.4%
|
5
71.4%
|
26
63.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
7
100%
|
8
100%
|
19
100%
|
7
100%
|
41
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| White |
6
85.7%
|
8
100%
|
19
100%
|
7
100%
|
40
97.6%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Chinese |
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ECOG Score (Count of Participants) | |||||
| 0 |
1
14.3%
|
4
50%
|
7
36.8%
|
1
14.3%
|
13
31.7%
|
| 1 |
5
71.4%
|
4
50%
|
12
63.2%
|
5
71.4%
|
26
63.4%
|
| 2 |
1
14.3%
|
0
0%
|
0
0%
|
1
14.3%
|
2
4.9%
|
| 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Treatment Phase Part A: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for E7820 |
|---|---|
| Description | |
| Time Frame | Day 1 or 8: 0.5-48 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic (PK) analysis set included all participants who had sufficient PK data to derive at least 1 PK parameter. Participants who were evaluable at a particular time point for this endpoint were included in the assessment. |
| Arm/Group Title | Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: E7820 50 mg Fasted |
|---|---|---|
| Arm/Group Description | Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase. | Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase. |
| Measure Participants | 12 | 14 |
| Mean (Standard Deviation) [nanogram*hour per milliliter (ng*hr/mL)] |
12500
(3510)
|
11500
(3490)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Phase Part A: E7820 50 mg Fed, Treatment Phase Part A: E7820 50 mg Fasted |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Log-transformed pharmacokinetic parameters were fit using a mixed effects model with sequence, treatment, period and sequence as fixed effects and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed to obtain the treatment estimates. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric Least Square (LS) Mean Ratio |
| Estimated Value | 1.06 | |
| Confidence Interval |
(2-Sided) 90% 0.97 to 1.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Treatment Phase Part A: AUC(0-t): Area Under the Plasma Concentration- Time Curve From Time 0 to t for E7820 |
|---|---|
| Description | |
| Time Frame | Day 1 or 8: 0.5-48 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who had sufficient PK data to derive at least 1 PK parameter. |
| Arm/Group Title | Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: E7820 50 mg Fasted |
|---|---|---|
| Arm/Group Description | Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase. | Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase. |
| Measure Participants | 14 | 15 |
| Mean (Standard Deviation) [ng*hr/mL] |
11200
(3680)
|
10500
(3460)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Phase Part A: E7820 50 mg Fed, Treatment Phase Part A: E7820 50 mg Fasted |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Log-transformed pharmacokinetic parameters were fit using a mixed effects model with sequence, treatment, period and sequence as fixed effects and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed to obtain the treatment estimates. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
| Estimated Value | 1.11 | |
| Confidence Interval |
(2-Sided) 90% 1.02 to 1.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Treatment Phase Part A: Cmax: Maximum Observed Plasma Concentration for E7820 |
|---|---|
| Description | |
| Time Frame | Day 1 or 8: 0.5-48 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set included all participants who had sufficient PK data to derive at least 1 PK parameter. |
| Arm/Group Title | Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: E7820 50 mg Fasted |
|---|---|---|
| Arm/Group Description | Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase. | Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase. |
| Measure Participants | 14 | 15 |
| Mean (Standard Deviation) [nanogram per milliliter (ng/mL)] |
1030
(311)
|
901
(242)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Phase Part A: E7820 50 mg Fed, Treatment Phase Part A: E7820 50 mg Fasted |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Equivalence | |
| Comments | Log-transformed pharmacokinetic parameters were fit using a mixed effects model with sequence, treatment, period and sequence as fixed effects and participant as a random effect. Geometric LS means and geometric LS mean ratio were back-transformed to obtain the treatment estimates. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
| Estimated Value | 1.13 | |
| Confidence Interval |
(2-Sided) 90% 1 to 1.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Treatment Phase Part B: Maximum Tolerated Dose (MTD) of E7820 BID Dosing Schedule |
|---|---|
| Description | MTD defined as the highest dose level at which no more than 1 of 6 participants experienced a dose-limiting toxicity(DLT), with the next higher dose having at least 2 of 3 or 2 of 6 participants experiencing DLTs. DLTs were defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events(CTCAE) Version 4.03 as: Neutropenia less than(<) 0.5*10^9/liter(L) for greater than(>) 5 days; neutropenia <1*10^9/L with fever; thrombocytopenia <25*10^9/L accompanied by bleeding or thrombocytopenia <10*10^9/L; any Grade 3 or 4 nonhematological toxicity for which the study drug could not be excluded as a cause (other than nausea, vomiting or diarrhea in the absence of appropriate prophylaxis) with the following clarification: Grade 3 or 4 nonhematological laboratory abnormalities for which there was no expected clinical correlation would not be considered DLTs; treatment delay of >14 days required to recover from E7820-related toxicities. |
| Time Frame | Up to Cycle 6 (Cycle length =28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| MTD was assessed in safety analysis set. The safety analysis set included all participants who received at least 1 dose of study drug. |
| Arm/Group Title | Treatment Phase Part B: All Participants |
|---|---|
| Arm/Group Description | Participants received E7820 50 mg or 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. |
| Measure Participants | 26 |
| Number [mg] |
50
|
| Title | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) |
|---|---|
| Description | BOR based on RECIST 1.1 for target and non-target lesions is complete response (CR) or partial response (PR) for >4 weeks or stable disease (SD) for >5 weeks from first dose. CR: disappearance of target and non-target lesions, normalization of tumor marker level, all lymph nodes must be non- pathological in size (<10 millimeter [mm] short axis). PR: at least 30% decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Time Frame | From first dose of study drug (Baseline) up to approximately 6.6 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The efficacy evaluable analysis set: all participants with a completed tumor assessment at Baseline (Chest, Abdomen and Pelvis scans) and at least 1 complete posttreatment tumor assessment (as per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). Overall number of participants analyzed signifies participants evaluable for this measure. |
| Arm/Group Title | Extension Phase Part A: E7820 100 mg | Treatment and Extension Phase Part B: E7820 50 mg | Treatment and Extension Phase Part B: E7820 60 mg |
|---|---|---|---|
| Arm/Group Description | Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 100 mg, once daily, tablet, orally, under fasted condition, during 28-day cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. |
| Measure Participants | 13 | 18 | 5 |
| Complete response |
0
0%
|
0
0%
|
0
0%
|
| Partial response |
0
0%
|
0
0%
|
0
0%
|
| Stable disease |
3
42.9%
|
12
150%
|
2
10.5%
|
| Title | Extension Phase Part A, and Treatment and Extension Phase Part B: Duration of Response |
|---|---|
| Description | Duration of response based on RECIST 1.1 for target and non-target lesions is the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever came first. CR: disappearance of target and non-target lesions,normalization of tumor marker level,all lymph nodes must be non-pathological in size(<10 mm short axis). PR: at least 30% decrease in SOD of target lesions,taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD:at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions,taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Time Frame | From date of first documented confirmed CR/PR until date of first documentation of PD or death (approximately up to 6.6 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Duration of response was not analyzed since no participants had best overall response of CR or PR in the study. |
| Arm/Group Title | Extension Phase Part A: E7820 100 mg | Treatment and Extension Phase Part B: E7820 50 mg | Treatment and Extension Phase Part B: E7820 60 mg |
|---|---|---|---|
| Arm/Group Description | Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 100 mg, once daily, tablet, orally, under fasted condition, during 28-day cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. |
| Measure Participants | 0 | 0 | 0 |
| Title | Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) |
|---|---|
| Description | PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions. For PD: participants with best response of PD have been reported. For Death: participants with death known to have died at any point have been reported. |
| Time Frame | From first dose date to the date of the first documentation of confirmed PD or death (approximately up to 6.6 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The efficacy evaluable set. Due to lack of available summarized data, data has been presented only descriptively in terms of number of participants who were known to have died and number of who had PD. |
| Arm/Group Title | Extension Phase Part A: E7820 100 mg | Treatment and Extension Phase Part B: E7820 50 mg | Treatment and Extension Phase Part B: E7820 60 mg |
|---|---|---|---|
| Arm/Group Description | Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 100 mg, once daily, tablet, orally, under fasted condition, during 28-day cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. |
| Measure Participants | 13 | 18 | 7 |
| Death |
11
157.1%
|
14
175%
|
5
26.3%
|
| PD |
9
128.6%
|
6
75%
|
2
10.5%
|
| Title | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; physical examinations; and regular measurement of vital signs, ECG, and multiple-gated acquisition (MUGA) scans or echocardiograms. |
| Time Frame | From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all participants who received at least 1 dose of study drug. |
| Arm/Group Title | Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: E7820 50 mg Fasted | Extension Phase Part A: E7820 100 mg | Treatment and Extension Phase Part B: E7820 50 mg | Treatment and Extension Phase Part B: E7820 60 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase. | Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase. | Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 100 mg, once daily, tablet, orally, under fasted condition, during 28-day cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. |
| Measure Participants | 15 | 15 | 15 | 19 | 7 |
| TEAEs |
7
100%
|
7
87.5%
|
15
78.9%
|
19
271.4%
|
7
17.1%
|
| SAEs |
0
0%
|
1
12.5%
|
5
26.3%
|
10
142.9%
|
6
14.6%
|
Adverse Events
| Time Frame | From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: E7820 50 mg Fasted | Extension Phase Part A: E7820 100 mg | Treatment and Extension Phase Part B: E7820 50 mg | Treatment and Extension Phase Part B: E7820 60 mg | |||||
| Arm/Group Description | Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase. | Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase. | Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 100 mg, once daily, tablet, orally, under fasted condition, during 28-day cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development. | |||||
All Cause Mortality |
||||||||||
| Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: E7820 50 mg Fasted | Extension Phase Part A: E7820 100 mg | Treatment and Extension Phase Part B: E7820 50 mg | Treatment and Extension Phase Part B: E7820 60 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/15 (73.3%) | 11/15 (73.3%) | 11/15 (73.3%) | 14/19 (73.7%) | 5/7 (71.4%) | |||||
Serious Adverse Events |
||||||||||
| Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: E7820 50 mg Fasted | Extension Phase Part A: E7820 100 mg | Treatment and Extension Phase Part B: E7820 50 mg | Treatment and Extension Phase Part B: E7820 60 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 1/15 (6.7%) | 5/15 (33.3%) | 10/19 (52.6%) | 6/7 (85.7%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Leukopenia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Neutropenia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Thrombocytopenia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Cardiac disorders | ||||||||||
| Pericardial effusion | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Ear and labyrinth disorders | ||||||||||
| Tinnitus | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Endocrine disorders | ||||||||||
| Inappropriate antidiuretic hormone secretion | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 1 |
| Constipation | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Duodenal ulcer haemorrhage | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Dysphagia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Nausea | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 2/7 (28.6%) | 2 |
| Oesophageal ulcer | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Pancreatic enzyme abnormality | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Small intestinal obstruction | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Upper gastrointestinal haemorrhage | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Vomiting | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 2/7 (28.6%) | 2 |
| General disorders | ||||||||||
| Malaise | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Pyrexia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 2/19 (10.5%) | 3 | 0/7 (0%) | 0 |
| Immune system disorders | ||||||||||
| Food allergy | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Infections and infestations | ||||||||||
| Bronchitis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Clostridium difficile infection | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Neutropenic sepsis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Urosepsis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Muscle abscess | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Investigations | ||||||||||
| Hepatic enzyme abnormal | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Aspartate aminotransferase increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 3 | 0/7 (0%) | 0 |
| Alanine aminotransferase increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 4 | 0/7 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Tumour haemorrhage | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Headache | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Spinal cord compression | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Dyspnoea | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 2 | 0/7 (0%) | 0 |
| Epistaxis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Haemoptysis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Pulmonary embolism | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Pruritus | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Rash | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Vascular disorders | ||||||||||
| Orthostatic hypotension | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Treatment Phase Part A: E7820 50 mg Fed | Treatment Phase Part A: E7820 50 mg Fasted | Extension Phase Part A: E7820 100 mg | Treatment and Extension Phase Part B: E7820 50 mg | Treatment and Extension Phase Part B: E7820 60 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/15 (46.7%) | 6/15 (40%) | 14/15 (93.3%) | 19/19 (100%) | 7/7 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 8/19 (42.1%) | 19 | 0/7 (0%) | 0 |
| Leukopenia | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 1/15 (6.7%) | 4 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Lymphopenia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Neutropenia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 2 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Thrombocytopenia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 2 | 1/19 (5.3%) | 2 | 2/7 (28.6%) | 4 |
| Cardiac disorders | ||||||||||
| Atrioventricular block | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Tachycardia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 3 | 0/7 (0%) | 0 |
| Endocrine disorders | ||||||||||
| Hyperthyroidism | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Hypothyroidism | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Eye disorders | ||||||||||
| Conjunctivitis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Myopia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Ocular hyperaemia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||
| Abdominal discomfort | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 2 | 0/7 (0%) | 0 |
| Abdominal distension | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Abdominal mass | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Abdominal pain | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 2/15 (13.3%) | 2 | 6/19 (31.6%) | 7 | 2/7 (28.6%) | 3 |
| Abdominal pain upper | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Ascites | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 4 | 0/7 (0%) | 0 |
| Constipation | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 4/15 (26.7%) | 4 | 7/19 (36.8%) | 11 | 4/7 (57.1%) | 5 |
| Diarrhoea | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/15 (13.3%) | 2 | 10/19 (52.6%) | 12 | 1/7 (14.3%) | 1 |
| Dyspepsia | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 3/15 (20%) | 4 | 2/19 (10.5%) | 2 | 2/7 (28.6%) | 3 |
| Dysphagia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Haematemesis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Haemorrhoids | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Mouth ulceration | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Nausea | 2/15 (13.3%) | 2 | 1/15 (6.7%) | 1 | 2/15 (13.3%) | 4 | 5/19 (26.3%) | 8 | 3/7 (42.9%) | 4 |
| Pancreatitis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Retching | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Stomatitis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/15 (13.3%) | 2 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Tongue ulceration | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Vomiting | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/15 (13.3%) | 3 | 5/19 (26.3%) | 6 | 2/7 (28.6%) | 7 |
| General disorders | ||||||||||
| Asthenia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Axillary pain | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Chest discomfort | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Chills | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Facial pain | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Fatigue | 0/15 (0%) | 0 | 1/15 (6.7%) | 2 | 5/15 (33.3%) | 7 | 10/19 (52.6%) | 19 | 4/7 (57.1%) | 5 |
| Feeling cold | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Influenza like illness | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 2 | 0/7 (0%) | 0 |
| Local swelling | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 2 | 0/7 (0%) | 0 |
| Malaise | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Necrosis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Oedema peripheral | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/15 (13.3%) | 2 | 3/19 (15.8%) | 4 | 1/7 (14.3%) | 1 |
| Pyrexia | 1/15 (6.7%) | 1 | 1/15 (6.7%) | 1 | 2/15 (13.3%) | 2 | 4/19 (21.1%) | 6 | 0/7 (0%) | 0 |
| Thirst | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Infections and infestations | ||||||||||
| Erysipelas | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Escherichia urinary tract infection | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Gastroenteritis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 2 | 0/7 (0%) | 0 |
| Localised infection | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Lower respiratory tract infection | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 3 | 0/7 (0%) | 0 |
| Nail infection | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Nasopharyngitis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/15 (13.3%) | 3 | 2/19 (10.5%) | 3 | 1/7 (14.3%) | 1 |
| Oesophageal candidiasis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Oral candidiasis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 2/7 (28.6%) | 2 |
| Oral herpes | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Osteomyelitis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Otitis media | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Rash pustular | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Rhinitis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 2 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Skin infection | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Upper respiratory tract infection | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/15 (13.3%) | 2 | 2/19 (10.5%) | 4 | 2/7 (28.6%) | 2 |
| Urinary tract infection | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 2/19 (10.5%) | 2 | 0/7 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Contusion | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Fall | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 2 | 0/7 (0%) | 0 |
| Procedural hypotension | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Wound haemorrhage | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 2 | 0/7 (0%) | 0 |
| Investigations | ||||||||||
| Alanine aminotransferase increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 4/15 (26.7%) | 9 | 3/19 (15.8%) | 3 | 2/7 (28.6%) | 4 |
| Aspartate aminotransferase increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/15 (13.3%) | 7 | 2/19 (10.5%) | 5 | 1/7 (14.3%) | 2 |
| Blood albumin decreased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 2 | 0/7 (0%) | 0 |
| Blood alkaline phosphatase increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/15 (13.3%) | 5 | 3/19 (15.8%) | 4 | 2/7 (28.6%) | 2 |
| Blood bilirubin increased | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 5/15 (33.3%) | 7 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Blood cholesterol increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Blood creatine phosphokinase increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 2 |
| Blood creatinine increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Blood glucose increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 2 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Blood lactate dehydrogenase increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 2 |
| Blood magnesium decreased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Blood phosphorus decreased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 2 | 0/7 (0%) | 0 |
| Blood potassium decreased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 3 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Blood thyroid stimulating hormone increased | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Gamma-glutamyltransferase increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Lipase increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 2 |
| Neutrophil count increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Platelet count decreased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Protein total decreased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Vitamin D decreased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Weight decreased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 5/19 (26.3%) | 7 | 0/7 (0%) | 0 |
| White blood cell count increased | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 4/15 (26.7%) | 4 | 7/19 (36.8%) | 7 | 1/7 (14.3%) | 1 |
| Dehydration | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Hyperglycaemia | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 2/15 (13.3%) | 6 | 3/19 (15.8%) | 4 | 1/7 (14.3%) | 1 |
| Hypocalcaemia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Hypokalaemia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 2 | 1/7 (14.3%) | 1 |
| Hypomagnesaemia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 2 | 0/7 (0%) | 0 |
| Hyponatraemia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/15 (13.3%) | 2 | 2/19 (10.5%) | 4 | 1/7 (14.3%) | 2 |
| Type 2 diabetes mellitus | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 3 | 1/7 (14.3%) | 1 |
| Arthritis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Back pain | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 1/15 (6.7%) | 2 | 4/19 (21.1%) | 5 | 1/7 (14.3%) | 1 |
| Bone pain | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Bursitis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 1 |
| Flank pain | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Joint swelling | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Muscle spasms | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/15 (13.3%) | 2 | 2/19 (10.5%) | 2 | 1/7 (14.3%) | 1 |
| Musculoskeletal chest pain | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 3/19 (15.8%) | 3 | 0/7 (0%) | 0 |
| Musculoskeletal pain | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 1 |
| Myalgia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 2/19 (10.5%) | 2 | 1/7 (14.3%) | 1 |
| Myopathy | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Pain in extremity | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Trismus | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Cognitive disorder | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Dizziness | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 6/19 (31.6%) | 7 | 0/7 (0%) | 0 |
| Dizziness postural | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Headache | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 2 | 3/19 (15.8%) | 3 | 1/7 (14.3%) | 1 |
| Lethargy | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 2/15 (13.3%) | 4 | 7/19 (36.8%) | 7 | 1/7 (14.3%) | 1 |
| Neuralgia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Paraesthesia | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 1 |
| Psychiatric disorders | ||||||||||
| Affect lability | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Anxiety | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Depressed mood | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Insomnia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 6/19 (31.6%) | 8 | 1/7 (14.3%) | 1 |
| Renal and urinary disorders | ||||||||||
| Bladder spasm | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Haematuria | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 1 |
| Nocturia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||
| Nipple pain | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 3/15 (20%) | 5 | 3/19 (15.8%) | 5 | 2/7 (28.6%) | 3 |
| Dry throat | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Dysphonia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Dyspnoea | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 2/19 (10.5%) | 5 | 1/7 (14.3%) | 1 |
| Dyspnoea exertional | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Epistaxis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 2/19 (10.5%) | 4 | 0/7 (0%) | 0 |
| Haemoptysis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Oropharyngeal pain | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Painful respiration | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Pleural effusion | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Pleuritic pain | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Rhinorrhoea | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Sneezing | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Wheezing | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Alopecia | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Decubitus ulcer | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 2 | 0/7 (0%) | 0 |
| Dry skin | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 3/15 (20%) | 3 | 3/19 (15.8%) | 3 | 0/7 (0%) | 0 |
| Erythema | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Hair colour changes | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Hyperhidrosis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Nail disorder | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Night sweats | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Onychomadesis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Palmar-plantar erythrodysaesthesia syndrome | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Pruritus | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 3/15 (20%) | 3 | 0/19 (0%) | 0 | 0/7 (0%) | 0 |
| Rash | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 3/19 (15.8%) | 3 | 1/7 (14.3%) | 1 |
| Scab | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Skin fissures | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Skin lesion | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Vascular disorders | ||||||||||
| Haematoma | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 |
| Haemorrhage | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Hypertension | 1/15 (6.7%) | 1 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 2/19 (10.5%) | 2 | 2/7 (28.6%) | 3 |
| Hypotension | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Orthostatic hypotension | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
| Phlebitis | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 0/15 (0%) | 0 | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
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
| Name/Title | Eisai Medical Information |
|---|---|
| Organization | Eisai, Inc. |
| Phone | +1-888-274-2378 |
| esi_oncmedinfo@eisai.com |
Responsible Party:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01773421
Other Study ID Numbers:
- E7820-E044-110
- 2010-023655-28
First Posted:
Jan 23, 2013
Last Update Posted:
Jan 18, 2020
Last Verified:
Feb 1, 2018