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Varlitinib in Combination With Capecitabine for Advanced or Metastatic Biliary Tract Cancer (TreeTopp)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03093870
Recruitment Status : Completed
First Posted : March 28, 2017
Results First Posted : August 3, 2021
Last Update Posted : August 3, 2021
Sponsor:
Collaborators:
bioRASI, LLC
CMIC Co, Ltd. Japan
Syneos Health
Information provided by (Responsible Party):
ASLAN Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Biliary Tract Cancer
Interventions Drug: Varlitinib
Drug: Capecitabine
Drug: Placebo (for Varlitinib)
Enrollment 151
Recruitment Details Period 1: Safety lead-in, N=24. Period 2: Part 1, N=127
Pre-assignment Details Period 1: Safety lead-in phase had only 1 arm (Varlitinib and Capecitabine). Period 2: Part 1 phase had 2 arms (Varlitinib and Capecitabine vs Placebo and Capecitabine)
Arm/Group Title Varlitinib and Capecitabine - Safety Lead-In Varlitinib and Capecitabine - Part 1 Placebo and Capecitabine - Part 1
Hide Arm/Group Description

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Period Title: Overall Study
Started 24 64 63
Completed 0 23 22
Not Completed 24 41 41
Reason Not Completed
Withdrawal by Subject             2             6             5
Death             1             35             35
Radiographic disease progression             10             0             0
Clinical disease progression             1             0             0
Physician Decision             2             0             0
Adverse Event             7             0             0
Patient withdrew from treatment voluntarily due to intermittent constipation and anorexia             1             0             0
Lost to Follow-up             0             0             1
Arm/Group Title Varlitinib and Capecitabine - Safety Lead-In Varlitinib and Capecitabine - Part 1 Placebo and Capecitabine - Part 1 Total
Hide Arm/Group Description

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Total of all reporting groups
Overall Number of Baseline Participants 24 64 63 151
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Safety Lead-In Number Analyzed 24 participants 0 participants 0 participants 24 participants
58.5  (9.68) 58.5  (9.68)
Part 1 Number Analyzed 0 participants 64 participants 63 participants 127 participants
61.6  (10.39) 62.7  (11.19) 62.1  (10.76)
[1]
Measure Analysis Population Description: The study consists of Safety Lead-In (24 patients in Varlitinib + Capecitabine group) and Part 1 (64 patients in Varlitinib + Capecitabine group, 63 patients in Placebo + Capecitabine group)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Safety Lead-In Number Analyzed 24 participants 0 participants 0 participants 24 participants
Female
13
  54.2%
13
  54.2%
Male
11
  45.8%
11
  45.8%
Part 1 Number Analyzed 0 participants 64 participants 63 participants 127 participants
Female
20
  31.3%
30
  47.6%
50
  39.4%
Male
44
  68.8%
33
  52.4%
77
  60.6%
[1]
Measure Analysis Population Description: The study consists of Safety Lead-In (24 patients in Varlitinib + Capecitabine group) and Part 1 (64 patients in Varlitinib + Capecitabine group, 63 patients in Placebo + Capecitabine group)
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Overall Study Number Analyzed 24 participants 64 participants 63 participants 151 participants
Hispanic or Latino
4
  16.7%
1
   1.6%
1
   1.6%
6
   4.0%
Not Hispanic or Latino
20
  83.3%
63
  98.4%
62
  98.4%
145
  96.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Overall Study Number Analyzed 24 participants 64 participants 63 participants 151 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
9
  37.5%
42
  65.6%
47
  74.6%
98
  64.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   1.6%
0
   0.0%
1
   0.7%
White
12
  50.0%
21
  32.8%
16
  25.4%
49
  32.5%
More than one race
2
   8.3%
0
   0.0%
0
   0.0%
2
   1.3%
Unknown or Not Reported
1
   4.2%
0
   0.0%
0
   0.0%
1
   0.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
South Korea Number Analyzed 24 participants 64 participants 63 participants 151 participants
4
  16.7%
23
  35.9%
26
  41.3%
53
  35.1%
Hungary Number Analyzed 24 participants 64 participants 63 participants 151 participants
0
   0.0%
1
   1.6%
3
   4.8%
4
   2.6%
United States Number Analyzed 24 participants 64 participants 63 participants 151 participants
14
  58.3%
7
  10.9%
6
   9.5%
27
  17.9%
Japan Number Analyzed 24 participants 64 participants 63 participants 151 participants
0
   0.0%
15
  23.4%
13
  20.6%
28
  18.5%
Taiwan Number Analyzed 24 participants 64 participants 63 participants 151 participants
0
   0.0%
3
   4.7%
7
  11.1%
10
   6.6%
Poland Number Analyzed 24 participants 64 participants 63 participants 151 participants
0
   0.0%
3
   4.7%
1
   1.6%
4
   2.6%
Australia Number Analyzed 24 participants 64 participants 63 participants 151 participants
0
   0.0%
5
   7.8%
2
   3.2%
7
   4.6%
Spain Number Analyzed 24 participants 64 participants 63 participants 151 participants
0
   0.0%
7
  10.9%
5
   7.9%
12
   7.9%
Singapore Number Analyzed 24 participants 64 participants 63 participants 151 participants
6
  25.0%
0
   0.0%
0
   0.0%
6
   4.0%
BMI   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
BMI - Safety Lead-in Number Analyzed 24 participants 0 participants 0 participants 24 participants
36.85  (58.381) 36.85  (58.381)
BMI - Part 1 Number Analyzed 0 participants 64 participants 63 participants 127 participants
24.6  (4.69) 23.8  (4.52) 24.2  (4.60)
[1]
Measure Analysis Population Description: The study consists of Safety Lead-In (24 patients in Varlitinib + Capecitabine group) and Part 1 (64 patients in Varlitinib + Capecitabine group, 63 patients in Placebo + Capecitabine group)
1.Primary Outcome
Title Objective Response Rate (ORR) - Part 1
Hide Description Part 1: The ORR was defined as the number (%) of subjects with ≥ 1 visit response of complete response (CR) or partial response (PR). Data obtained up until progression, or until last evaluable assessment in the absence of progression, was included in the assessment of ORR, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression. Best overall RECIST Response (BOR) was calculated based on the overall visit responses from each RECIST assessment, i.e. the best response a subject had following randomization and prior to RECIST progression or the last evaluable assessment in the absence of RECIST progression. Categorization of BOR was based on the RECIST criteria using the following response categories: CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE).
Time Frame Data obtained up until progression, or until last evaluable assessment in the absence of progression, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression, up to 2 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib and Capecitabine Placebo and Capecitabine
Hide Arm/Group Description:

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Overall Number of Participants Analyzed 64 63
Measure Type: Count of Participants
Unit of Measure: Participants
Responders - CR
0
   0.0%
0
   0.0%
Responders - PR
6
   9.4%
3
   4.8%
Non-Responders - SD
29
  45.3%
34
  54.0%
Non-Responders - PD
24
  37.5%
24
  38.1%
Non-Responders - NE
5
   7.8%
2
   3.2%
2.Primary Outcome
Title Progression-free Survival (PFS) - Part 1
Hide Description Part 1: Progression-free survival (PFS) was defined as the time from randomization (or starting treatment for the Safety Lead-in) until the date of objective disease progression or death (by any cause in the absence of disease progression) regardless of whether the subject withdrew from randomized therapy or received another antitumor therapy prior to disease progression. Subjects who did not experience disease progression or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. However, if the patient progressed or died after ≥ 2 missed visits (12 weeks ± 5 days maximum), the subject was censored at the time of the latest evaluable RECIST assessment. The PFS time was based on the scan/assessment dates rather than visit dates.
Time Frame Time from randomization until date of objective disease progression or death (by any cause in absence of disease progression) regardless of whether subject withdrew from randomized therapy or received another antitumor therapy prior to PD, up to 2 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib and Capecitabine Placebo and Capecitabine
Hide Arm/Group Description:

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Overall Number of Participants Analyzed 49 47
Median (Inter-Quartile Range)
Unit of Measure: Months
2.83
(1.48 to 5.62)
2.79
(1.41 to 4.24)
3.Secondary Outcome
Title Object Response Rates (ORR) - Safety Lead-In
Hide Description The ORR rate was defined as the number (%) of subjects with ≥ 1 visit response of complete response (CR) or partial response (PR). Data obtained up until progression, or until last evaluable assessment in the absence of progression, was included in the assessment of ORR, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression. In all study parts, the primary assessment of ORR was based on the Full Analysis Set (FAS).
Time Frame Data obtained up until progression, or until last evaluable assessment in absence of progression, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression, up to 2 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib + Capecitabine
Hide Arm/Group Description:
This part of the study was a single arm, open-label design to assess the safety of varlitinib (300 mg administered BID every day) plus capecitabine (1000 mg/m2 administered BID every day for 14 days, followed by a 7-day rest period) in a small set of subjects (12 to 20 subjects) with 12 subjects completing the PK and ECG evaluations. Treatment was continued until disease progression, development of unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
Responders - CR
0
   0.0%
Responders - PR
1
   4.2%
Non-Responders - SD
5
  20.8%
Non-Responders - PD
9
  37.5%
Non-Responders - NE
9
  37.5%
4.Secondary Outcome
Title Overall Survival (OS) - Part 1
Hide Description Part 1: Overall survival (OS) was defined as the time from the date of randomization until death due to any cause. Any subject not known to have died at the time of the data cut-off was censored based on the last recorded date on which the subject was known to be alive.
Time Frame Time from the date of randomization until death due to any cause, up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib and Capecitabine Placebo and Capecitabine
Hide Arm/Group Description:

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Overall Number of Participants Analyzed 35 35
Median (Inter-Quartile Range)
Unit of Measure: Months
7.8
(4.5 to 11.5)
7.5 [1] 
(5.3 to NA)
[1]
The 75th percentile is Not Evaluable (NE), because the 75th percentile has not been reached yet (i.e. the data are too immature for that arm)
5.Secondary Outcome
Title Overall Survival (OS) - Safety Lead-In
Hide Description Part 1: Overall survival (OS) was defined as the time from the date of randomization until death due to any cause. Any subject not known to have died at the time of the data cut-off was censored based on the last recorded date on which the subject was known to be alive.
Time Frame Time from the date of randomization until death due to any cause, up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib + Capecitabine
Hide Arm/Group Description:
This part of the study was a single arm, open-label design to assess the safety of varlitinib (300 mg administered BID every day) plus capecitabine (1000 mg/m2 administered BID every day for 14 days, followed by a 7-day rest period) in a small set of subjects (12 to 20 subjects) with 12 subjects completing the PK and ECG evaluations. Treatment was continued until disease progression, development of unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
Alive
17
  70.8%
Withdrew Consent
2
   8.3%
Dead
4
  16.7%
Withdrew due to AE
1
   4.2%
6.Secondary Outcome
Title Duration of Response (DoR) - Part 1
Hide Description

Part 1: Duration of response (DoR) was defined as the time from the date of first documented response until the date of documented PD or death in the absence of disease progression. The end of the response should have coincided with the date of disease progression or death from any cause used for the PFS endpoint.

For Part 1, DoR was calculated based on data from the ICR of radiological data.

Time Frame Time from the date of first documented response until the date of documented PD or death in the absence of disease progression, up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Kaplan Meier median is presented for DoR. At the time of reporting, there were 3 censored observations in the V+C arm, none in the P+C arm. The observed number of responders in the trial was much lower than anticipated; 9 responders in total, 6 for varlitinib and 3 for placebo. Based on results of the primary endpoints, the follow-up analysis to provide more long-term efficacy data planned for when 70% of patients had experienced an OS event was not undertaken based on pre-specified criteria.
Arm/Group Title Varlitinib and Capecitabine Placebo and Capecitabine
Hide Arm/Group Description:

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Overall Number of Participants Analyzed 6 3
Median (Full Range)
Unit of Measure: Days
158
(43 to 158)
90
(48 to 246)
7.Secondary Outcome
Title Disease Control Rate DCR - Part 1
Hide Description

Part 1: DCR rate was defined as the number (%) of subjects with ≥ 1 visit response of CR or PR, or with SD for a minimum of 12 weeks (± 5 days) from randomization. Data obtained up until progression, or until last evaluable assessment in the absence of progression, were included in the assessment of DCR, regardless of whether subjects discontinued treatment or received a subsequent therapy prior to progression. For all study parts, the primary assessment of DCR was based on the FAS.

For Part 1, DCR was calculated based on data from the ICR

Time Frame Number (%) of subjects with ≥ 1 visit response of CR or PR, or with SD for a minimum of 12 weeks (± 5 days) from randomization.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib and Capecitabine Placebo and Capecitabine
Hide Arm/Group Description:

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Overall Number of Participants Analyzed 64 63
Measure Type: Count of Participants
Unit of Measure: Participants
Disease Control - CR
0
   0.0%
0
   0.0%
Disease Control - PR
6
   9.4%
3
   4.8%
Disease Control - SD for 12 weeks
12
  18.8%
16
  25.4%
No Disease Control - SD < 12 weeks
17
  26.6%
18
  28.6%
No Disease Control - PD
24
  37.5%
24
  38.1%
No Disease Control - NE
5
   7.8%
2
   3.2%
8.Secondary Outcome
Title Tumor Size - Part 1
Hide Description Part 1: The percentage change from baseline in tumor size at Week 12 (%ΔTSWk12) was a secondary endpoint for Part 1 and was used to present waterfall plots of the target lesion data in the Evaluable for Response (EFR) Population
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib and Capecitabine Placebo and Capecitabine
Hide Arm/Group Description:

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Overall Number of Participants Analyzed 51 51
Mean (Standard Deviation)
Unit of Measure: Percentage change from Baseline
18.1  (39.46) 22.6  (36.11)
9.Secondary Outcome
Title Number of Participants With Clinically Significant Laboratory Tests- Safety Lead-in
Hide Description Clinical laboratory tests (hematology, clinical chemistry, urinalysis) - Number of Participants with Clinically Significant Laboratory Tests.
Time Frame Subject screening visit to 28 days post last study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
No subjects reported with any CS values across majority of the hematologic, clinical chemistry, urinalysis parameters during the Safety Lead-In of the study
Arm/Group Title Varlitinib + Capecitabine
Hide Arm/Group Description:
This part of the study was a single arm, open-label design to assess the safety of varlitinib (300 mg administered BID every day) plus capecitabine (1000 mg/m2 administered BID every day for 14 days, followed by a 7-day rest period) in a small set of subjects (12 to 20 subjects) with 12 subjects completing the PK and ECG evaluations. Treatment was continued until disease progression, development of unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
10.Secondary Outcome
Title Number of Participants With Clinically Significant Laboratory Tests - Part 1
Hide Description Clinical laboratory tests (hematology, clinical chemistry, urinalysis) - Number of Participants with Clinically Significant Laboratory Tests.
Time Frame Subject screening visit to 28 days post last study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
No subjects reported with any CS values across majority of the hematologic, clinical chemistry and urinalysis parameters at the end of treatment.
Arm/Group Title Varlitinib and Capecitabine Placebo and Capecitabine
Hide Arm/Group Description:

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Overall Number of Participants Analyzed 64 63
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
11.Secondary Outcome
Title Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Safety Lead-In
Hide Description Number of participants with clinically significant change in vital signs (blood pressure [diastolic and systolic], heart rate, respiratory rate, body temperature) and physical examination.
Time Frame Subject screening visit to 28 days post last study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib + Capecitabine
Hide Arm/Group Description:
This part of the study was a single arm, open-label design to assess the safety of varlitinib (300 mg administered BID every day) plus capecitabine (1000 mg/m2 administered BID every day for 14 days, followed by a 7-day rest period) in a small set of subjects (12 to 20 subjects) with 12 subjects completing the PK and ECG evaluations. Treatment was continued until disease progression, development of unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
12.Secondary Outcome
Title Number of Participants With Clinically Significant Change in Vital Signs and Physical Examinations - Part 1
Hide Description Number of participants with clinically significant change in vital signs (blood pressure [diastolic and systolic], heart rate, respiratory rate, body temperature) and physical examination.
Time Frame Subject screening visit to 28 days post last study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib and Capecitabine Placebo and Capecitabine
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Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Overall Number of Participants Analyzed 64 63
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
13.Secondary Outcome
Title Number of Participants With ECG Parameters of Interest - Safety Lead-In
Hide Description Number of participants with ECG parameters of interest: Max. on-treatment QTcF Value: >450 to 480 msec, max. on-treatment QTcF Value: >480 to 500 msec, max. on-treatment QTcF Value: >500 msec, max. on-treatment QTcB Value: >450 to 480 msec, max. on-treatment QTcB Value: >480 to 500 msec, max. on-treatment QTcB Value: >500 msec, max. QTcF CFB Value: >30 to 60 msec, max. QTcF CFB Value: >60 msec, max. QTcB CFB Value: >30 to 60 msec, max. QTcB CFB Value: >60 msec.
Time Frame Subject screening visit to 28 days post last study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib + Capecitabine
Hide Arm/Group Description:
This part of the study was a single arm, open-label design to assess the safety of varlitinib (300 mg administered BID every day) plus capecitabine (1000 mg/m2 administered BID every day for 14 days, followed by a 7-day rest period) in a small set of subjects (12 to 20 subjects) with 12 subjects completing the PK and ECG evaluations. Treatment was continued until disease progression, development of unacceptable toxicity, withdrawal of consent, or death.
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
Maximum on-treatment QTcF Value: >450 to 480 msec 8
Maximum on-treatment QTcF Value: >480 to 500 msec 0
Maximum on-treatment QTcF Value: >500 msec 0
Maximum on-treatment QTcB Value: >450 to 480 msec 10
Maximum on-treatment QTcB Value: >480 to 500 msec 2
Maximum on-treatment QTcB Value: >500 msec 0
Maximum QTcF CFB Value: >30 to 60 msec 8
Maximum QTcF CFB Value: >60 msec 1
Maximum QTcB CFB Value: >30 to 60 msec 6
Maximum QTcB CFB Value: >60 msec 1
14.Secondary Outcome
Title Number of Participants With ECG Parameters of Interest - Part 1
Hide Description Number of participants with ECG parameters of interest: Max. on-treatment QTcF Value: <=450 msec, max. on-treatment QTcF Value: >450 to 480 msec, max. on-treatment QTcF Value: >480 to 500 msec, max. on-treatment QTcF Value: >500 msec, max. on-treatment QTcB Value: <=450 msec, max. on-treatment QTcB Value: >450 to 480 msec, max. on-treatment QTcB Value: >480 to 500 msec, max. on-treatment QTcB Value: >500 msec, max. QTcF CFB Value: <=30 msec, max. QTcF CFB Value: >30 to 60 msec, max. QTcF CFB Value: >60 msec, max. QTcB CFB Value: <=30 msec, max. QTcB CFB Value: >30 to 60 msec, max. QTcB CFB Value: >60 msec.
Time Frame Subject screening visit to 28 days post last study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Varlitinib and Capecitabine Placebo and Capecitabine
Hide Arm/Group Description:

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Overall Number of Participants Analyzed 64 63
Measure Type: Number
Unit of Measure: Participants
Maximum on-treatment QTcF Value: <=450 msec 53 57
Maximum on-treatment QTcF Value: >450 to 480 msec 10 6
Maximum on-treatment QTcF Value: >480 to 500 msec 0 0
Maximum on-treatment QTcF Value: >500 msec 1 0
Maximum on-treatment QTcB Value: <=450 msec 42 40
Maximum on-treatment QTcB Value: >450 to 480 msec 21 22
Maximum on-treatment QTcB Value: >480 to 500 msec 0 1
Maximum on-treatment QTcB Value: >500 msec 1 0
Maximum QTcF CFB Value: <=30 msec 56 57
Maximum QTcF CFB Value: >30 to 60 msec 7 4
Maximum QTcF CFB Value: >60 msec 0 1
Maximum QTcB CFB Value: <=30 msec 55 54
Maximum QTcB CFB Value: >30 to 60 msec 8 7
Maximum QTcB CFB Value: >60 msec 0 1
15.Secondary Outcome
Title ECOG Performance Status - Part 1
Hide Description

Eastern Cooperative Oncology Group (ECOG) Performance was clinically graded based on the following:

Grade 0 = Normal activity. Fully active, able to carry on all pre-disease performance without restriction.

Grade 1 = Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work).

Grade 2 = In bed < 50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.

Grade 3 = In bed > 50% of the time. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.

Grade 4 = 100% bedridden. Completely disabled. Cannot carry on any self- care. Totally confined to bed or chair.

Grade 5 = Death

Time Frame Subject screening visit to 28 days post last study drug administration
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Hide Analysis Population Description

For the Varlitinib 300 mg BID + Capecitabine treatment group, ECOG Performance Status scores ranged from 0 to 3 at EOT.

For the Placebo + Capecitabine treatment group, ECOG Performance Status scores ranged from 0 to 3 at EOT.

Arm/Group Title Varlitinib and Capecitabine Placebo and Capecitabine
Hide Arm/Group Description:

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Overall Number of Participants Analyzed 64 63
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Value Grade 0 - EOT Value Grade 0
16
  25.0%
11
  17.5%
Baseline Value Grade 0 - EOT Value Grade 1
13
  20.3%
10
  15.9%
Baseline Value Grade 0 - EOT Value Grade 2
0
   0.0%
2
   3.2%
Baseline Value Grade 0 - EOT Value Grade 3
4
   6.3%
1
   1.6%
Baseline Value Grade 0 - EOT Value Not done
4
   6.3%
2
   3.2%
Baseline Value Grade 1 - EOT Value Grade 0
1
   1.6%
5
   7.9%
Baseline Value Grade 1 - EOT Value Grade 1
10
  15.6%
25
  39.7%
Baseline Value Grade 1 - EOT Value Grade 2
5
   7.8%
2
   3.2%
Baseline Value Grade 1 - EOT Value Grade 3
0
   0.0%
0
   0.0%
Baseline Value Grade 1 - EOT Value Not done
11
  17.2%
5
   7.9%
Time Frame Subject screening visit to 28 days post last study drug administration, up to 2 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Varlitinib and Capecitabine - Safety Lead-In Varlitinib and Capecitabine - Part 1 Placebo and Capecitabine - Part 1
Hide Arm/Group Description

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Varlitinib: Varlitinib:300mg, oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Placebo (for Varlitinib): oral tablets, twice daily. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Capecitabine: 1000mg/m2, oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles. Number of cycles: until disease progression, unacceptable toxicity, withdrawal of consent, or death.

All-Cause Mortality
Varlitinib and Capecitabine - Safety Lead-In Varlitinib and Capecitabine - Part 1 Placebo and Capecitabine - Part 1
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/24 (8.33%)      35/64 (54.69%)      35/63 (55.56%)    
Hide Serious Adverse Events
Varlitinib and Capecitabine - Safety Lead-In Varlitinib and Capecitabine - Part 1 Placebo and Capecitabine - Part 1
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/24 (54.17%)      25/64 (39.06%)      27/63 (42.86%)    
Blood and lymphatic system disorders       
Anemia   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Embolism   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Blood culture positive   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Cardiac disorders       
Cardiac arrest   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Gastrointestinal disorders       
Enterocolitis   2/24 (8.33%)  0/64 (0.00%)  0/63 (0.00%) 
Abdominal Pain   1/24 (4.17%)  1/64 (1.56%)  2/63 (3.17%) 
Constipation   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Diarrhoea   1/24 (4.17%)  1/64 (1.56%)  0/63 (0.00%) 
Haematemesis   1/24 (4.17%)  0/64 (0.00%)  1/63 (1.59%) 
Nausea   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Small intestinal obstruction   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Vomiting   1/24 (4.17%)  4/64 (6.25%)  2/63 (3.17%) 
Haemorrhoidal haemorrhage   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Intestinal obstruction   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Small intestinal haemorrhage   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Abdominal pain upper   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Inguinal hernia   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
General disorders       
Asthenia   1/24 (4.17%)  1/64 (1.56%)  2/63 (3.17%) 
Pyrexia   1/24 (4.17%)  3/64 (4.69%)  0/63 (0.00%) 
Disease progression   0/24 (0.00%)  2/64 (3.13%)  2/63 (3.17%) 
Oedema peripheral   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
General physical health deterioration   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Pain   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Hepatobiliary disorders       
Bile duct obstruction   2/24 (8.33%)  2/64 (3.13%)  0/63 (0.00%) 
Cholangitis   1/24 (4.17%)  4/64 (6.25%)  4/63 (6.35%) 
Hyperbilirubinaemia   1/24 (4.17%)  4/64 (6.25%)  0/63 (0.00%) 
Hemobilia   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Bile duct stenosis   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Biliary dilatation   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Biliary sepsis   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Jaundice   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Biloma   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Cholangiolitis   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Cholecystitis   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Jaundice cholestatic   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Infections and infestations       
Lung Infection   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Septic shock   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Pneumonia   0/24 (0.00%)  2/64 (3.13%)  1/63 (1.59%) 
Hepatobiliary infection   0/24 (0.00%)  1/64 (1.56%)  1/63 (1.59%) 
Biliary tract infection   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Liver abscess   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Peritonitis bacterial   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Injury, poisoning and procedural complications       
Procedural complication   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Investigations       
Blood bilirubin increased   0/24 (0.00%)  5/64 (7.81%)  5/63 (7.94%) 
Blood creatinine increased   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Metabolism and nutrition disorders       
Dehydration   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Hypercalcaemia   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Hyponatremia   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Metabolic acidosis   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Decreased appetite   0/24 (0.00%)  1/64 (1.56%)  1/63 (1.59%) 
Nervous system disorders       
Hypoxic-ischaemic encephalopathy   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Ischaemic stroke   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Spinal cord compression   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Toxic leukoencephalopathy   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Cerebrovascular accident   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Dyspnoea   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Renal and urinary disorders       
Acute kidney injury   2/24 (8.33%)  2/64 (3.13%)  1/63 (1.59%) 
Hematuria   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Hernia   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Respiratory, thoracic and mediastinal disorders       
Aspiration   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Respiratory Failure   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Acute respiratory failure   0/24 (0.00%)  0/64 (0.00%)  1/63 (1.59%) 
Skin and subcutaneous tissue disorders       
Rash generalized   1/24 (4.17%)  0/64 (0.00%)  0/63 (0.00%) 
Erythema multiforme   0/24 (0.00%)  1/64 (1.56%)  0/63 (0.00%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Varlitinib and Capecitabine - Safety Lead-In Varlitinib and Capecitabine - Part 1 Placebo and Capecitabine - Part 1
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/24 (100.00%)      64/64 (100.00%)      59/63 (93.65%)    
Blood and lymphatic system disorders       
Anaemia   6/24 (25.00%)  7 13/64 (20.31%)  30 14/63 (22.22%)  27
Gastrointestinal disorders       
Nausea   15/24 (62.50%)  29 33/64 (51.56%)  58 14/63 (22.22%)  19
Diarrhoea   13/24 (54.17%)  31 26/64 (40.63%)  43 16/63 (25.40%)  19
Vomiting   11/24 (45.83%)  27 22/64 (34.38%)  30 11/63 (17.46%)  18
Abdominal Pain   9/24 (37.50%)  12 16/64 (25.00%)  27 12/63 (19.05%)  20
Constipation   8/24 (33.33%)  19 9/64 (14.06%)  9 9/63 (14.29%)  9
Stomatitis   6/24 (25.00%)  9 7/64 (10.94%)  8 8/63 (12.70%)  8
Dyspepsia   5/24 (20.83%)  8 7/64 (10.94%)  9 4/63 (6.35%)  4
Ascites   4/24 (16.67%)  4 3/64 (4.69%)  3 4/63 (6.35%)  4
Abdominal Distension   7/24 (29.17%)  13 4/64 (6.25%)  5 2/63 (3.17%)  2
Abdominal Pain Upper   3/24 (12.50%)  3 3/64 (4.69%)  3 2/63 (3.17%)  2
Gastrooesophageal Reflux Disease   2/24 (8.33%)  2 3/64 (4.69%)  4 2/63 (3.17%)  2
Dry mouth   3/24 (12.50%)  3 1/64 (1.56%)  1 0/63 (0.00%)  0
Enterocolitis   2/24 (8.33%)  8 0/64 (0.00%)  0 1/63 (1.59%)  1
Faeces discolored   2/24 (8.33%)  4 0/64 (0.00%)  0 0/63 (0.00%)  0
Hematemesis   2/24 (8.33%)  5 0/64 (0.00%)  0 2/63 (3.17%)  2
Oral pain   2/24 (8.33%)  2 1/64 (1.56%)  1 0/63 (0.00%)  0
General disorders       
Fatigue   14/24 (58.33%)  35 16/64 (25.00%)  33 12/63 (19.05%)  17
Pyrexia   10/24 (41.67%)  18 15/64 (23.44%)  23 11/63 (17.46%)  13
Asthenia   5/24 (20.83%)  9 11/64 (17.19%)  20 7/63 (11.11%)  9
Malaise   2/24 (8.33%)  2 8/64 (12.50%)  14 4/63 (6.35%)  4
Chills   5/24 (20.83%)  7 6/64 (9.38%)  7 2/63 (3.17%)  2
Mucosal Inflammation   0/24 (0.00%)  0 5/64 (7.81%)  8 2/63 (3.17%)  2
Oedema Peripheral   7/24 (29.17%)  12 4/64 (6.25%)  5 3/63 (4.76%)  3
Early satiety   2/24 (8.33%)  2 0/64 (0.00%)  0 0/63 (0.00%)  0
Influenza like illness   2/24 (8.33%)  3 0/64 (0.00%)  0 0/63 (0.00%)  0
Hepatobiliary disorders       
Cholangitis   2/24 (8.33%)  5 5/64 (7.81%)  10 5/63 (7.94%)  8
Hyperbilirubinaemia   3/24 (12.50%)  8 7/64 (10.94%)  16 1/63 (1.59%)  7
Bile duct obstruction   2/24 (8.33%)  8 2/64 (3.13%)  4 0/63 (0.00%)  0
Infections and infestations       
Pneumonia   0/24 (0.00%)  0 5/64 (7.81%)  5 1/63 (1.59%)  1
Urinary tract infection   3/24 (12.50%)  3 1/64 (1.56%)  1 1/63 (1.59%)  1
Investigations       
Blood Bilirubin Increased   8/24 (33.33%)  17 28/64 (43.75%)  71 14/63 (22.22%)  30
Blood Creatinine Increased   3/24 (12.50%)  5 15/64 (23.44%)  26 3/63 (4.76%)  3
Aspartate Aminotransferase Increased   5/24 (20.83%)  10 9/64 (14.06%)  19 7/63 (11.11%)  11
Platelet Count Decreased   4/24 (16.67%)  16 8/64 (12.50%)  13 8/63 (12.70%)  11
Alanine Aminotransferase Increased   4/24 (16.67%)  7 10/64 (15.63%)  22 5/63 (7.94%)  8
Neutrophil Count Decreased   2/24 (8.33%)  5 3/64 (4.69%)  7 5/63 (7.94%)  21
Weight Decreased   3/24 (12.50%)  4 3/64 (4.69%)  3 1/63 (1.59%)  1
Blood alkaline phosphatase increased   2/24 (8.33%)  2 2/64 (3.13%)  3 3/63 (4.76%)  3
Gamma-glutamyltransferase increased   2/24 (8.33%)  2 1/64 (1.56%)  2 4/63 (6.35%)  4
International normalised ratio increased   2/24 (8.33%)  3 1/64 (1.56%)  3 0/63 (0.00%)  0
Metabolism and nutrition disorders       
Decreased Appetite   12/24 (50.00%)  33 25/64 (39.06%)  49 11/63 (17.46%)  15
Hypoalbuminaemia   3/24 (12.50%)  3 6/64 (9.38%)  11 5/63 (7.94%)  7
Hypokalaemia   10/24 (41.67%)  20 2/64 (3.13%)  6 2/63 (3.17%)  2
Hyponatraemia   7/24 (29.17%)  10 4/64 (6.25%)  5 0/63 (0.00%)  0
Hypoglycemia   2/24 (8.33%)  2 3/64 (4.69%)  4 0/63 (0.00%)  0
Dehydration   6/24 (25.00%)  11 0/64 (0.00%)  0 0/63 (0.00%)  0
Hypomagnesaemia   3/24 (12.50%)  5 1/64 (1.56%)  1 0/63 (0.00%)  0
Hyperkalaemia   2/24 (8.33%)  2 2/64 (3.13%)  2 1/63 (1.59%)  2
Hypocalcaemia   2/24 (8.33%)  2 2/64 (3.13%)  2 1/63 (1.59%)  1
Musculoskeletal and connective tissue disorders       
Back Pain   7/24 (29.17%)  7 4/64 (6.25%)  5 4/63 (6.35%)  6
Myalgia   2/24 (8.33%)  2 3/64 (4.69%)  3 0/63 (0.00%)  0
Muscular weakness   3/24 (12.50%)  4 1/64 (1.56%)  2 0/63 (0.00%)  0
Bursitis   2/24 (8.33%)  2 0/64 (0.00%)  0 0/63 (0.00%)  0
Musculoskeletal pain   2/24 (8.33%)  2 2/64 (3.13%)  2 1/63 (1.59%)  1
Nervous system disorders       
Peripheral Sensory Neuropathy   1/24 (4.17%)  2 5/64 (7.81%)  8 2/63 (3.17%)  2
Dizziness   7/24 (29.17%)  11 4/64 (6.25%)  5 2/63 (3.17%)  2
Dysgeusia   2/24 (8.33%)  4 5/64 (7.81%)  6 1/63 (1.59%)  1
Hypoaesthesia   2/24 (8.33%)  2 0/64 (0.00%)  0 0/63 (0.00%)  0
Paraesthesia   2/24 (8.33%)  3 1/64 (1.56%)  1 0/63 (0.00%)  0
Psychiatric disorders       
Insomnia   2/24 (8.33%)  4 3/64 (4.69%)  4 3/63 (4.76%)  3
Anxiety   2/24 (8.33%)  2 1/64 (1.56%)  1 2/63 (3.17%)  2
Depression   2/24 (8.33%)  2 0/64 (0.00%)  0 0/63 (0.00%)  0
Renal and urinary disorders       
Acute Kidney Injury   2/24 (8.33%)  9 5/64 (7.81%)  6 1/63 (1.59%)  1
Proteinuria   5/24 (20.83%)  6 3/64 (4.69%)  6 2/63 (3.17%)  2
Respiratory, thoracic and mediastinal disorders       
Dyspnoea   5/24 (20.83%)  16 5/64 (7.81%)  5 4/63 (6.35%)  4
Cough   3/24 (12.50%)  4 4/64 (6.25%)  4 3/63 (4.76%)  3
Dyspnoea exertional   3/24 (12.50%)  4 1/64 (1.56%)  1 0/63 (0.00%)  0
Dysphonia   2/24 (8.33%)  2 0/64 (0.00%)  0 0/63 (0.00%)  0
Epistaxis   2/24 (8.33%)  4 2/64 (3.13%)  2 0/63 (0.00%)  0
Rhinitis allergic   2/24 (8.33%)  2 0/64 (0.00%)  0 0/63 (0.00%)  0
Skin and subcutaneous tissue disorders       
Palmar-plantar Erythrodysaethesia Syndrome   6/24 (25.00%)  18 20/64 (31.25%)  32 19/63 (30.16%)  37
Pruritus   0/24 (0.00%)  0 11/64 (17.19%)  13 5/63 (7.94%)  5
Rash   4/24 (16.67%)  7 8/64 (12.50%)  10 4/63 (6.35%)  7
Skin Hyperpigmentation   0/24 (0.00%)  0 5/64 (7.81%)  5 1/63 (1.59%)  1
Vascular disorders       
Hypotension   6/24 (25.00%)  8 4/64 (6.25%)  4 0/63 (0.00%)  0
Indicates events were collected by systematic assessment
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
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Name/Title: Study Director
Organization: ASLAN Pharmaceuticals
Phone: +65 6222 4235
EMail: contact@aslanpharma.com
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Responsible Party: ASLAN Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03093870    
Other Study ID Numbers: ASLAN001-009
First Submitted: March 16, 2017
First Posted: March 28, 2017
Results First Submitted: May 17, 2021
Results First Posted: August 3, 2021
Last Update Posted: August 3, 2021