Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of Oxycodone/Naloxone Compared to OxyContin in Korean Cancer Patients (NCT NCT01313780)

NCT ID: NCT01313780

Last Updated: 2017-12-22

Results Overview

Change of pain intensity from 0(No pain) to 10(worst pain imaginable) after 4 weeks treatment .

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

128 participants

Primary outcome timeframe

4weeks

Results posted on

2017-12-22

Participant Flow

ITT set(Safety analysis) was 128(64:64) patients, but Missing primary efficacy data: 7 patients, Violation of inclusion/exclusion criteria: 4. So, FAS(Efficacy analysis) set population was 117(oxycodone/naloxone group: 58: Oxycodone: 59).

Participant milestones

Participant milestones
Measure	Oxycodone and Naloxone Trade name is TARGIN. Daily dose can be titrated up to 40mg B.I.D.	Oxycodone Trade name is Oxycontin. Daily dose can be titrated up to 40mg B.I.D.
Overall Study STARTED	58	59
Overall Study COMPLETED	33	31
Overall Study NOT COMPLETED	25	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Oxycodone and Naloxone Trade name is TARGIN. Daily dose can be titrated up to 40mg B.I.D.	Oxycodone Trade name is Oxycontin. Daily dose can be titrated up to 40mg B.I.D.
Overall Study Lack of Efficacy	4	2
Overall Study Adverse Event	6	11
Overall Study Withdrawal by Subject	2	8
Overall Study Protocol Violation	10	4
Overall Study missing data	3	3

Baseline Characteristics

A Study to Evaluate Efficacy and Safety of Oxycodone/Naloxone Compared to OxyContin in Korean Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oxycodone and Naloxone n=58 Participants Trade name is TARGIN. Daily dose can be titrated up to 40mg B.I.D.	Oxycodone n=59 Participants Trade name is Oxycontin. Daily dose can be titrated up to 40mg B.I.D.	Total n=117 Participants Total of all reporting groups
Age, Customized <39years	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Age, Customized 40~49years	7 participants n=5 Participants	5 participants n=7 Participants	12 participants n=5 Participants
Age, Customized 50~59years	19 participants n=5 Participants	17 participants n=7 Participants	36 participants n=5 Participants
Age, Customized 60~69 years	14 participants n=5 Participants	23 participants n=7 Participants	37 participants n=5 Participants
Age, Customized 70~79 years	17 participants n=5 Participants	11 participants n=7 Participants	28 participants n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	20 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	39 Participants n=7 Participants	82 Participants n=5 Participants
Region of Enrollment Korea, Republic of	58 participants n=5 Participants	59 participants n=7 Participants	117 participants n=5 Participants

PRIMARY outcome

Timeframe: 4weeks

Population: Analysis of FAS: 117.

Change of pain intensity from 0(No pain) to 10(worst pain imaginable) after 4 weeks treatment .

Outcome measures

Outcome measures
Measure	Oxycodone and Naloxone n=58 Participants Trade name is TARGIN. Daily dose can be titrated up to 40mg B.I.D.	Oxycodone n=59 Participants Trade name is Oxycontin. Daily dose can be titrated up to 40mg B.I.D.
Change of Pain Intensity From Baseline(visit1) to 4weeks.(visit3)	1.586 units on a scale Standard Deviation 2.217	1.559 units on a scale Standard Deviation 2.215

SECONDARY outcome

Timeframe: 4 weeks

Population: FAS analysis, but Oxycodone/naloxone group was missed 15 patients data and Oxycodone group was missed 23 patients data.

The change of bowel habits from baseline (Visit 1) in bowel habits at Week 4 was investigated, and was categorized as 'improved', 'unchanged', and 'worsened'.

Outcome measures

Outcome measures
Measure	Oxycodone and Naloxone n=43 Participants Trade name is TARGIN. Daily dose can be titrated up to 40mg B.I.D.	Oxycodone n=36 Participants Trade name is Oxycontin. Daily dose can be titrated up to 40mg B.I.D.
Change in Bowel Habits. Unchanged	31 participants	20 participants
Change in Bowel Habits. worsened	7 participants	11 participants
Change in Bowel Habits. Improved	5 participants	5 participants

Adverse Events

Oxycodone and Naloxone

Serious events: 15 serious events

Other events: 55 other events

Deaths: 0 deaths

Oxycodone

Serious events: 28 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Taewon Kim

Seoul Asan Hospital

Phone: 82-2-3010-3910

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Oxycodone and Naloxone n=64 participants at risk Oxycodone and naloxone: Trade name is TARGIN.	Oxycodone n=64 participants at risk oxycodone : Trade name is Oxycontin
Immune system disorders anaphylactic shock	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Investigations leukocytosis	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Investigations neutropenia	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Investigations Thrombocytopenia	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders Fever	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders General condition worse	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders Sweating	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Endocrine disorders Disorder of adrenal gland	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders aggravated abdominal distension	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Anorexia	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders ascitis	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders colonic obstruction	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Distension/bloating, abdominal	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders protruding mass in oral cavity	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders rectal cancer progression	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Vomiting	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders worsening vomitting	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Hepatobiliary disorders cancer progression(gallbladder)	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Hepatobiliary disorders jaundice	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Hepatobiliary disorders progress of disease	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Infections and infestations pneumonia	3.1% 2/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Blood and lymphatic system disorders left neck neoplasm (lymph node)	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Blood and lymphatic system disorders leg edema	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Metabolism and nutrition disorders Elevation of ALT	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Metabolism and nutrition disorders Elevation of AST	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Metabolism and nutrition disorders Glucose, serum-low (hypoglycemia)	3.1% 2/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Metabolism and nutrition disorders Electro imbalance	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Musculoskeletal and connective tissue disorders lower extremity weakness	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Musculoskeletal and connective tissue disorders Rt. Clavicle metasis	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Nervous system disorders Anxiety	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Nervous system disorders both, limb numbness	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Nervous system disorders delirium	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Nervous system disorders Dizziness	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Nervous system disorders hand tremor	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Nervous system disorders HYPERALGESIA	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Nervous system disorders Seizure	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Nervous system disorders somnolence	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Nervous system disorders headache	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders Pain	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	3.1% 2/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.

Other adverse events
Measure	Oxycodone and Naloxone n=64 participants at risk Oxycodone and naloxone: Trade name is TARGIN.	Oxycodone n=64 participants at risk oxycodone : Trade name is Oxycontin
Immune system disorders anaphylactic shock	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Blood and lymphatic system disorders Anemia	1.6% 1/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Blood and lymphatic system disorders leukocytosis	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Blood and lymphatic system disorders Megablastic anemia	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Blood and lymphatic system disorders neutropenia	3.1% 2/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Cardiac disorders Hypotension	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders cold sweating	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders Fatigue	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders Fatigue (asthenia, lethargy, malaise)	4.7% 3/64 • Number of events 3 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	4.7% 3/64 • Number of events 3 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders Fever	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders General condition worse	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders General weakness	1.6% 1/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Nervous system disorders Insomnia	4.7% 3/64 • Number of events 3 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders night fever	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders Sweating	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders Sweating (diaphoresis)	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
General disorders Weight loss	1.6% 1/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Skin and subcutaneous tissue disorders itching sense(WB)	1.6% 1/64 • Number of events 2 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Skin and subcutaneous tissue disorders Pruritus/itching	3.1% 2/64 • Number of events 3 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	4.7% 3/64 • Number of events 5 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Skin and subcutaneous tissue disorders skin lesion on ear	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Skin and subcutaneous tissue disorders skin nodule	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Skin and subcutaneous tissue disorders whole body itching	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Endocrine disorders Disorder of adrenal gland	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Abdominal palpable mass	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders aggravated abdominal distension	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Anorexia	12.5% 8/64 • Number of events 14 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	6.2% 4/64 • Number of events 4 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders ascitis	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders colonic obstruction	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Constipation	46.9% 30/64 • Number of events 36 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	54.7% 35/64 • Number of events 37 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Diarrhea	6.2% 4/64 • Number of events 4 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Distension/bloating, abdominal	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders heartburn	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Heartburn/dyspepsia	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	4.7% 3/64 • Number of events 3 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders indigestion	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Nausea	15.6% 10/64 • Number of events 11 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	28.1% 18/64 • Number of events 19 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders protruding mass in oral cavity	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders rectal cancer progression	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders reducing oral intake	0.00% 0/64 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	1.6% 1/64 • Number of events 1 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.
Gastrointestinal disorders Vomiting	12.5% 8/64 • Number of events 9 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.	10.9% 7/64 • Number of events 7 • 4 weeks Subjects will be asked to voluntarily report adverse event information any time, and the information will be also checked at phone visits and regular visits during the treatment period through interviews and medical examination by the investigator.