Phase II Study of SyB D-0701 for Radiotherapy-Induced Nau... | NCT01700140

Label	Type	Intervention Names
SyB D-0701: high dose group	Experimental	Drug: SyB D-0701
SyB D-0701: low dose group	Experimental	Drug: SyB D-0701 Drug: Placebo
placebo group	Placebo Comparator	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
SyB D-0701	Drug	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch, High dose group (30.00 mg): SyB D-0701 15 cm2 patch + SyB D-0701 25 cm2 patch] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.

Measure	Description	Time Frame
Complete Control (no Signs of Emesis or Moderate to Severe Nausea and no Use of Rescue Medication) Rate From the Start of Radiotherapy Until 24 Hours After the Third Irradiation	The complete control rate was defined as the percentage of subjects who had no emesis and no moderate or more severe nausea and who used no rescue drugs during the period from the time of the first irradiation to 24 hours after the third irradiation.	72 hours

Measure	Description	Time Frame
Complete Response (no Signs of Emesis and no Use of Rescue Medication) Rate From the Start of Radiotherapy Until 24 Hours After the Third Irradiation	The complete response rate was defined as the percentage of subjects who had no emesis and who used no rescue drugs during the period from the time of the first irradiation to 24 hours after the third irradiation.	72 hours

Eligibility Module

Eligibility Criteria

Inclusion Criteria Patients must satisfy the following conditions listed below.

Patients with histologically verified malignant tumors
Patients receiving radiotherapy alone who are scheduled for at least 3 fractions, each at a radiation dose of 1.5 to 3.0 Gy
Cancer patients scheduled for radiotherapy over a field of at least 100 cm2 (50 cm2 or more in cases of irradiation of the vertebrae only) that includes the abdomen and pelvis (region with upper edge at the 11th thoracic vertebrae and lower edge at pelvic cavity)
Patients not scheduled to receive anti-tumor agents between the first and the fifth day of radiotherapy. If the patient has a history of anti-tumor agent therapy, however, at the time of the patient's registration, at least 5 days must have elapsed since drug administration was terminated, and the patient must not be scheduled to receive any anti-tumor agent from the first to the fifth day of radiotherapy
Male patients who are surgically sterilized, or who agree to practice adequate contraception during the study
Female patients of child-bearing potential who agree to practice adequate contraception during the study
Patients whose performance status (PS) of Eastern Cooperative Oncology Group (ECOG) is 0 to 2
Patients who were at least 20 years of age when their consent was obtained
Patients who have given consent in writing to participate in the study with full understanding of the explanatory documents

Exclusion Criteria Patients who satisfy any of the following conditions will not be enrolled in the study.

Patients with nausea and/or emesis; patients who also have intestinal obstruction, vestibular dysfunction (e.g., epilepsy), Meniere's syndrome, cerebral metastasis, electrolyte imbalance (hypercalcemia, hyperglycemia, hyponatremia), uremia, etc., and patients for whom it is judged that there is a high probability that their nausea or emesis arises from the aforementioned causes. Registration is possible, however, for patients with motion sickness (vehicle sickness) or patients with temporary nausea/emesis arising from routine activities.
Patients with primary or metastasized brain tumors who show signs of elevated intracranial pressure
Patients who previously received radiotherapy to the brain or to the region that includes the abdomen and pelvis (region with upper edge at the 11th thoracic vertebrae and lower edge at pelvic cavity)
Patients who take drugs that affect the evaluation of nausea or emesis (rescue medication and 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, neurokinin 1 (NK1) receptor antagonists, anxiolytics, psychotropic drug, opioid analgesics and corticosteroid [systemic administration] except for rescue medication)
Patients with abnormal findings (e.g., erythema, rash, wounds) at sites where the study drug has been applied
Patients with a history of hypersensitivity to study drug ingredients or to other 5-HT3 receptor antagonists
Patients with a history of allergy involving dermal symptoms
Patients with clear signs of infection (including viral infection)
Patients with complications from drug or alcohol dependence, or with a history of the same
Patients who have participated in some type of clinical study (including physician-initiated clinical studies or clinical research) within 3 months prior to their registration for the present study and who have been given a study drug (including drugs not yet approved). Patients can be registered for this study, however, if they have participated in a clinical study, etc., in which only drugs already approved have been used.
Patients with serious hepatic or renal damage [Grade 3 or above in the Common Terminology Criteria for Adverse Events (CTCAE) (ver. 4.0-JCOG)]
Patients with cardiac dysfunction
Patients who are pregnant, who might be pregnant or who are currently lactating
Other patients judged as unsuitable by the investigator or sub-investigators

Facility	Status	City	State	ZIP	Country	Contacts
Research site		Nagoya	Aichi-ken		Japan
Research site

ID	Title	Description
FG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Complete Control (no Signs of Emesis or Moderate to Severe Nausea and no Use of Rescue Medication) Rate From the Start of Radiotherapy Until 24 Hours After the Third Irradiation

The complete control rate was defined as the percentage of subjects who had no emesis and no moderate or more severe nausea and who used no rescue drugs during the period from the time of the first irradiation to 24 hours after the third irradiation.

Per protocol set:

Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.

Posted

Number

Percentage of participants

72 hours

ID	Title	Description
OG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG001	SyB D-0701: Low Dose Group	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG002	SyB D-0701: High Dose Group	Study drug patches [High dose group (30.00 mg): SyB D-0701 15 cm2 patch (11.25 mg) + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.

Units	Counts
Participants	OG00056 OG00159 OG00260

Title

Denominators

Categories

Title	Measurements
	OG00085.7 OG00184.7 OG00293.3

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact		1.0000						2-Sided							No	Superiority or Other
OG000 OG002		Fisher Exact		0.2284

Secondary

Complete Response (no Signs of Emesis and no Use of Rescue Medication) Rate From the Start of Radiotherapy Until 24 Hours After the Third Irradiation

The complete response rate was defined as the percentage of subjects who had no emesis and who used no rescue drugs during the period from the time of the first irradiation to 24 hours after the third irradiation.

Per protocol set:

Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.

Posted

Number

Percentage of participants

72 hours

ID	Title	Description
OG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG001	SyB D-0701: Low Dose Group	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG002	SyB D-0701: High Dose Group

Secondary

Time to First Emesis

Time from the start of radiotherapy to the onset of first emesis. The median (50% point) of time to first emesis was estimated.

Per protocol set:

Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.

Posted

Median

95% Confidence Interval

Hours

24-72 hours

ID	Title	Description
OG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG001	SyB D-0701: Low Dose Group	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG002	SyB D-0701: High Dose Group	Study drug patches [High dose group (30.00 mg): SyB D-0701 15 cm2 patch (11.25 mg) + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.

Secondary

Time to First Nausea

Time from the start of radiotherapy to the onset of first nausea. The median (50% point) of time to first nausea was estimated.

Per protocol set:

Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.

Posted

Median

95% Confidence Interval

Hours

24-72 hours

ID	Title	Description
OG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG001	SyB D-0701: Low Dose Group	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG002	SyB D-0701: High Dose Group	Study drug patches [High dose group (30.00 mg): SyB D-0701 15 cm2 patch (11.25 mg) + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.

Secondary

Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3

Complete control rate within 24 hours after each irradiation, from the first to the third fraction of radiotherapy.

The complete control rate was defined as the percentage of subjects who had no emesis and no moderate or more severe nausea and who used no rescue drugs.

Per protocol set:

Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.

Posted

Number

Percentage of participants

24-72 hours

ID	Title	Description
OG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG001	SyB D-0701: Low Dose Group	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG002	SyB D-0701: High Dose Group

Secondary

Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3

Complete response rate within 24 hours after each irradiation, from the first to the third fraction of radiotherapy.

The complete response rate was defined as the percentage of subjects who had no emesis and who used no rescue drugs.

Per protocol set:

Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.

Posted

Number

Percentage of participants

24-72 hours

ID	Title	Description
OG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG001	SyB D-0701: Low Dose Group	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG002	SyB D-0701: High Dose Group

Secondary

Adverse Events

Adverse event is any untoward medical occurrence experienced by a subject irrespective of causal relationship with the study drug, and includes the unexpected signs, clinically significant fluctuations of laboratory data, and aggravation of disease, symptoms or complications. Adverse events are coded using the preferred terms (PT) of Medical Dictionary for Regulatory Activities (MedDRA) version 15.0.

Safety population:

The safety population consisted of all subjects enrolled, except for subjects with Good Clinical Practice (GCP) non-compliance and those who failed to receive the study treatment.

Posted

Number

Participants

Up to 192 hours

ID	Title	Description
OG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG001	SyB D-0701: Low Dose Group	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.

Secondary

Severe (Grade 3 or More) Adverse Events

The severity of AEs were graded on a 5-point scale (Grade 1 to 5) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe or medically significant but not immediately life-threatening, Grade 4: Life-threatening consequences, Grade 5: Death related to AE

Safety population:

The safety population consisted of all subjects enrolled, except for subjects with GCP non-compliance and those who failed to receive the study treatment.

Posted

Number

Number of events

Up to 192 hours

ID	Title	Description
OG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG001	SyB D-0701: Low Dose Group	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
OG002

Secondary

Skin Manifestations at Study Drug Application Site

The investigator or sub-investigator recorded skin manifestations observed after removal of the study drug.

Skin manifestations were counted for each type of patches (placebo patch, SyB D-0701 15 cm2 patch, SyB D-0701 25 cm2 patch).

Skin manifestations were counted for each type of patch applied to the subjects in the safety population.

Placebo patch : 60-1+63+60=182 (One subject in placebo group did not applied 15 cm2 patch.)
SyB D-0701 15 cm2 patch : 62
SyB D-0701 25 cm2 patch : 62+63=125

Posted

Number

Number of events

Up to 192 hours

ID	Title	Description
OG000	Placebo Patch	Placebo 15 cm2 patch was applied to subjects in placebo group and low dose group. Placebo 25 cm2 patch was applied to subjects in placebo group.
OG001	SyB D-0701 15 cm2 Patch	SyB D-0701 15 cm2 patch (11.25 mg) was applied to subjects in high dose group.
OG002	SyB D-0701 25 cm2 Patch	SyB D-0701 25 cm2 patch (18.75 mg) was applied to subjects in low dose group and high dose group.

Other Adverse Events

Term	Organ System	Source Vocabulary	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0012 affected63 at risk EG0020 affected62 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0014 affected63 at risk EG0020 affected62 at risk
Palpitations	Cardiac disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Conjunctivitis	Eye disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0022 affected62 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA Ver 15.0	EG0003 affected60 at risk EG0013 affected63 at risk EG0021 affected62 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Constipation	Gastrointestinal disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG00114 affected63 at risk EG0027 affected62 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Ver 15.0	EG0009 affected60 at risk EG0016 affected63 at risk EG0023 affected62 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0012 affected63 at risk EG0020 affected62 at risk
Nausea	Gastrointestinal disorders	MedDRA Ver 15.0	EG00010 affected60 at risk EG0018 affected63 at risk EG0029 affected62 at risk
Vomiting	Gastrointestinal disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0012 affected63 at risk EG0020 affected62 at risk
Application site dermatitis	General disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Application site erythema	General disorders	MedDRA Ver 15.0	EG0006 affected60 at risk EG0019 affected63 at risk EG0029 affected62 at risk
Application site pruritus	General disorders	MedDRA Ver 15.0	EG0009 affected60 at risk EG0015 affected63 at risk EG00210 affected62 at risk
Application site rash	General disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Fatigue	General disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Malaise	General disorders	MedDRA Ver 15.0	EG0002 affected60 at risk EG0012 affected63 at risk EG0022 affected62 at risk
Oedema peripheral	General disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Pyrexia	General disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Application site vesicles	General disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Application site papules	General disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0011 affected63 at risk EG0022 affected62 at risk
Application site swelling	General disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Disease progression	General disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Cystitis	Infections and infestations	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Nasopharyngitis	Infections and infestations	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Urethritis	Infections and infestations	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Post procedural infection	Infections and infestations	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Gastroenteritis radiation	Injury, poisoning and procedural complications	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Radiation associated pain	Injury, poisoning and procedural complications	MedDRA Ver 15.0	EG0003 affected60 at risk EG0011 affected63 at risk EG0022 affected62 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Alanine aminotransferase increased	Investigations	MedDRA Ver 15.0	EG0001 affected60 at risk EG0013 affected63 at risk EG0020 affected62 at risk
Aspartate aminotransferase increased	Investigations	MedDRA Ver 15.0	EG0001 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Blood bilirubin increased	Investigations	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Blood creatinine increased	Investigations	MedDRA Ver 15.0	EG0001 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Blood potassium decreased	Investigations	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Blood uric acid increased	Investigations	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
C-reactive protein increased	Investigations	MedDRA Ver 15.0	EG0001 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Glucose urine present	Investigations	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Lymphocyte count decreased	Investigations	MedDRA Ver 15.0	EG00030 affected60 at risk EG00133 affected63 at risk EG00229 affected62 at risk
Neutrophil count decreased	Investigations	MedDRA Ver 15.0	EG0003 affected60 at risk EG0012 affected63 at risk EG0023 affected62 at risk
Neutrophil count increased	Investigations	MedDRA Ver 15.0	EG0002 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Platelet count decreased	Investigations	MedDRA Ver 15.0	EG0002 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Protein total decreased	Investigations	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Weight decreased	Investigations	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Weight increased	Investigations	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
White blood cell count decreased	Investigations	MedDRA Ver 15.0	EG00016 affected60 at risk EG00113 affected63 at risk EG00214 affected62 at risk
White blood cell count increased	Investigations	MedDRA Ver 15.0	EG0002 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Platelet count increased	Investigations	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0022 affected62 at risk
Blood pressure increased	Investigations	MedDRA Ver 15.0	EG0001 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA Ver 15.0	EG0002 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Ver 15.0	EG0002 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Periarthritis	Musculoskeletal and connective tissue disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Ver 15.0	EG0003 affected60 at risk EG0012 affected63 at risk EG0020 affected62 at risk
Dysgeusia	Nervous system disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Headache	Nervous system disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Insomnia	Psychiatric disorders	MedDRA Ver 15.0	EG0004 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Anxiety disorder	Psychiatric disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Dysuria	Renal and urinary disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Haematuria	Renal and urinary disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Pollakiuria	Renal and urinary disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Proteinuria	Renal and urinary disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0012 affected63 at risk EG0021 affected62 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Laryngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Eczema asteatotic	Skin and subcutaneous tissue disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0010 affected63 at risk EG0021 affected62 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0010 affected63 at risk EG0020 affected62 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA Ver 15.0	EG0001 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Ver 15.0	EG0000 affected60 at risk EG0011 affected63 at risk EG0020 affected62 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Ver 15.0	EG0006 affected60 at risk EG0014 affected63 at risk EG0023 affected62 at risk

ID	Term
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
BG001	SyB D-0701: Low Dose Group	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
BG002	SyB D-0701: High Dose Group	Study drug patches [High dose group (30.00 mg): SyB D-0701 15 cm2 patch (11.25 mg) + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo Group	Study drug patches (Placebo group: SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 placebo patch) assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.	1	60	51	60
EG001	SyB D-0701: Low Dose Group	Study drug patches [Low dose group (18.75 mg): SyB D-0701 15 cm2 placebo patch + SyB D-0701 25 cm2 patch (18.75mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.	0	63	55	63
EG002	SyB D-0701: High Dose Group	Study drug patches [High dose group (30.00 mg): SyB D-0701 15 cm2 patch (11.25 mg) + SyB D-0701 25 cm2 patch (18.75 mg)] assigned at the Case Registration Center are applied to either the right or left upper arm at 12 to 24 hours prior to the start of radiotherapy and left as is until 24 hours after completion of the third irradiation.	0	62	45	62