Radiotherapy-induced Nausea and Vomiting (RINV)
Conditions
Brief summary
The purpose of this study is to explore the dose response of SyB D-0701 for preventing nausea and emesis associated with radiotherapy (fractionated/localized irradiation) in cancer patients scheduled to receive radiotherapy (fractionated/localized irradiation) alone.
Detailed description
Exploratory study of dose response of SyB D-0701 to preventing effects for nausea and emesis associated with radiotherapy (fractionated/localized irradiation)
Interventions
DRUGSyB D-0701
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.
DRUGPlacebo
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.
Sponsors
SymBio Pharmaceuticals
Study design
Intervention model
PARALLEL
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must satisfy the following conditions listed below. 1. Patients with histologically verified malignant tumors 2. Patients receiving radiotherapy alone who are scheduled for at least 3 fractions, each at a radiation dose of 1.5 to 3.0 Gy 3. 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) 4. 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 5. Male patients who are surgically sterilized, or who agree to practice adequate contraception during the study 6. Female patients of child-bearing potential who agree to practice adequate contraception during the study 7. Patients whose performance status (PS) of Eastern Cooperative Oncology Group (ECOG) is 0 to 2 8. Patients who were at least 20 years of age when their consent was obtained 9. 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. 1. 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. 2. Patients with primary or metastasized brain tumors who show signs of elevated intracranial pressure 3. 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) 4. 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) 5. Patients with abnormal findings (e.g., erythema, rash, wounds) at sites where the study drug has been applied 6. Patients with a history of hypersensitivity to study drug ingredients or to other 5-HT3 receptor antagonists 7. Patients with a history of allergy involving dermal symptoms 8. Patients with clear signs of infection (including viral infection) 9. Patients with complications from drug or alcohol dependence, or with a history of the same 10. 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. 11. Patients with serious hepatic or renal damage \[Grade 3 or above in the Common Terminology Criteria for Adverse Events (CTCAE) (ver. 4.0-JCOG)\] 12. Patients with cardiac dysfunction 13. Patients who are pregnant, who might be pregnant or who are currently lactating 14. Other patients judged as unsuitable by the investigator or sub-investigators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 72 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Emesis | 24-72 hours | Time from the start of radiotherapy to the onset of first emesis. The median (50% point) of time to first emesis was estimated. |
| Time to First Nausea | 24-72 hours | Time from the start of radiotherapy to the onset of first nausea. The median (50% point) of time to first nausea was estimated. |
| Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | 24-72 hours | 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. |
| 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 | 72 hours | 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. |
| Adverse Events | Up to 192 hours | 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. |
| Severe (Grade 3 or More) Adverse Events | Up to 192 hours | 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 |
| Skin Manifestations at Study Drug Application Site | Up to 192 hours | 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). |
| Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | 24-72 hours | 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 56 |
| 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. | 59 |
| 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. | 60 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Aggravation of symptoms | 1 | 0 | 0 |
| Overall Study | Discontinuation of radiotherapy | 1 | 0 | 0 |
| Overall Study | Inclusion/exclusion criteria deviation | 1 | 4 | 0 |
| Overall Study | Use of chemotherapy or surgical therapy | 0 | 1 | 0 |
| Overall Study | Use of rescue drugs | 3 | 3 | 1 |
Baseline characteristics
| Characteristic | SyB D-0701: Low Dose Group | Total | Placebo Group | SyB D-0701: High Dose Group |
|---|---|---|---|---|
| Age, Customized 20-40 years | 7 Participants | 13 Participants | 3 Participants | 3 Participants |
| Age, Customized 40-50 years | 8 Participants | 26 Participants | 11 Participants | 7 Participants |
| Age, Customized 50-60 years | 13 Participants | 41 Participants | 11 Participants | 17 Participants |
| Age, Customized 60-70 years | 14 Participants | 40 Participants | 14 Participants | 12 Participants |
| Age, Customized 70≤ years | 17 Participants | 55 Participants | 17 Participants | 21 Participants |
| Alcohol consumption history Absent | 32 Participants | 108 Participants | 36 Participants | 40 Participants |
| Alcohol consumption history Present | 27 Participants | 67 Participants | 20 Participants | 20 Participants |
| Complication Absent | 11 Participants | 23 Participants | 2 Participants | 10 Participants |
| Complication Present | 48 Participants | 152 Participants | 54 Participants | 50 Participants |
| Diseases in the past 5 years Absent | 29 Participants | 74 Participants | 23 Participants | 22 Participants |
| Diseases in the past 5 years Present | 30 Participants | 101 Participants | 33 Participants | 38 Participants |
| History of radiotherapy Absent | 54 Participants | 167 Participants | 53 Participants | 60 Participants |
| History of radiotherapy Present | 5 Participants | 8 Participants | 3 Participants | 0 Participants |
| History of recent chemotherapy Absent | 36 Participants | 111 Participants | 37 Participants | 38 Participants |
| History of recent chemotherapy Present | 23 Participants | 64 Participants | 19 Participants | 22 Participants |
| History of smoking habit Absent | 31 Participants | 99 Participants | 29 Participants | 39 Participants |
| History of smoking habit Present | 28 Participants | 76 Participants | 27 Participants | 21 Participants |
| Metastasis Absent | 24 Participants | 92 Participants | 32 Participants | 36 Participants |
| Metastasis Present | 35 Participants | 83 Participants | 24 Participants | 24 Participants |
| Motion sickness (vehicle sickness) Absent | 57 Participants | 166 Participants | 54 Participants | 55 Participants |
| Motion sickness (vehicle sickness) Present | 2 Participants | 9 Participants | 2 Participants | 5 Participants |
| Nausea/emesis Absent | 59 Participants | 175 Participants | 56 Participants | 60 Participants |
| Nausea/emesis Present | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Performance status 0 | 41 Participants | 130 Participants | 39 Participants | 50 Participants |
| Performance status 1 | 16 Participants | 38 Participants | 14 Participants | 8 Participants |
| Performance status 2 | 2 Participants | 7 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 35 Participants | 108 Participants | 38 Participants | 35 Participants |
| Sex: Female, Male Male | 24 Participants | 67 Participants | 18 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 51 / 60 | 55 / 63 | 45 / 62 |
| serious Total, serious adverse events | 1 / 60 | 0 / 63 | 0 / 62 |
Outcome results
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.
Time frame: 72 hours
Population: Per protocol set:~Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Group | 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 | 85.7 Percentage of participants |
| SyB D-0701: Low Dose Group | 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 | 84.7 Percentage of participants |
| SyB D-0701: High Dose Group | 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 | 93.3 Percentage of participants |
p-value: 1Fisher Exact
p-value: 0.2284Fisher Exact
p-value: 0.2549Cochran-Armitage test
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.
Time frame: Up to 192 hours
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Group | Adverse Events | Number of subjects with any adverse event | 51 Participants |
| Placebo Group | Adverse Events | Number of subjects with adverse drug reaction | 14 Participants |
| Placebo Group | Adverse Events | Number of subjects with SAE | 1 Participants |
| Placebo Group | Adverse Events | Number of death | 0 Participants |
| SyB D-0701: Low Dose Group | Adverse Events | Number of death | 0 Participants |
| SyB D-0701: Low Dose Group | Adverse Events | Number of subjects with any adverse event | 55 Participants |
| SyB D-0701: Low Dose Group | Adverse Events | Number of subjects with SAE | 0 Participants |
| SyB D-0701: Low Dose Group | Adverse Events | Number of subjects with adverse drug reaction | 17 Participants |
| SyB D-0701: High Dose Group | Adverse Events | Number of death | 0 Participants |
| SyB D-0701: High Dose Group | Adverse Events | Number of subjects with adverse drug reaction | 16 Participants |
| SyB D-0701: High Dose Group | Adverse Events | Number of subjects with SAE | 0 Participants |
| SyB D-0701: High Dose Group | Adverse Events | Number of subjects with any adverse event | 45 Participants |
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.
Time frame: 24-72 hours
Population: Per protocol set:~Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Group | Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Second irradiation | 90.9 Percentage of participants |
| Placebo Group | Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | First irradiation | 91.1 Percentage of participants |
| Placebo Group | Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Third irradiation | 89.1 Percentage of participants |
| SyB D-0701: Low Dose Group | Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Second irradiation | 94.7 Percentage of participants |
| SyB D-0701: Low Dose Group | Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | First irradiation | 89.8 Percentage of participants |
| SyB D-0701: Low Dose Group | Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Third irradiation | 96.4 Percentage of participants |
| SyB D-0701: High Dose Group | Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | First irradiation | 98.3 Percentage of participants |
| SyB D-0701: High Dose Group | Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Third irradiation | 94.9 Percentage of participants |
| SyB D-0701: High Dose Group | Complete Control Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Second irradiation | 98.3 Percentage of participants |
Comparison: Statistical analysis for complete control rate after the first irradiationp-value: 1Fisher Exact
Comparison: Statistical analysis for complete control rate after the first irradiationp-value: 0.1051Fisher Exact
Comparison: Statistical analysis for complete control rate after the second irradiationp-value: 0.4856Fisher Exact
Comparison: Statistical analysis for complete control rate after the second irradiationp-value: 0.1047Fisher Exact
Comparison: Statistical analysis for complete control rate after the third irradiationp-value: 0.1617Fisher Exact
Comparison: Statistical analysis for complete control rate after the third irradiationp-value: 0.3099Fisher Exact
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.
Time frame: 72 hours
Population: Per protocol set:~Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Group | 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 | 89.3 Percentage of participants |
| SyB D-0701: Low Dose Group | 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 | 88.1 Percentage of participants |
| SyB D-0701: High Dose Group | 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 | 96.7 Percentage of participants |
p-value: 1Fisher Exact
p-value: 0.1527Fisher Exact
p-value: 0.1864Cochran-Armitage test
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.
Time frame: 24-72 hours
Population: Per protocol set:~Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Group | Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Second irradiation | 94.5 Percentage of participants |
| Placebo Group | Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | First irraditation | 91.1 Percentage of participants |
| Placebo Group | Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Third irradiation | 92.7 Percentage of participants |
| SyB D-0701: Low Dose Group | Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Second irradiation | 96.5 Percentage of participants |
| SyB D-0701: Low Dose Group | Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | First irraditation | 91.5 Percentage of participants |
| SyB D-0701: Low Dose Group | Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Third irradiation | 98.2 Percentage of participants |
| SyB D-0701: High Dose Group | Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | First irraditation | 98.3 Percentage of participants |
| SyB D-0701: High Dose Group | Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Third irradiation | 100.0 Percentage of participants |
| SyB D-0701: High Dose Group | Complete Response Rate Within 24 Hours After Each Irradiation From Sessions 1 to 3 | Second irradiation | 98.3 Percentage of participants |
Comparison: Statistical analysis for complete response rate after the first irradiationp-value: 1Fisher Exact
Comparison: Statistical analysis for complete response rate after the first irradiationp-value: 0.1051Fisher Exact
Comparison: Statistical analysis for complete response rate after the second irradiationp-value: 0.6761Fisher Exact
Comparison: Statistical analysis for complete response rate after the second irradiationp-value: 0.3513Fisher Exact
Comparison: Statistical analysis for complete response rate after the third irradiationp-value: 0.206Fisher Exact
Comparison: Statistical analysis for complete response rate after the third irradiationp-value: 0.0511Fisher Exact
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
Time frame: Up to 192 hours
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : hyponatraemia | 0 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : C-reactive protein increased | 1 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : urethritis | 0 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : blood alkaline phosphatase increased | 0 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : lymphocyte count decreased | 3 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : nausea | 2 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : white blood cell count decreased | 3 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : neutrophil count increased | 1 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : decreased appetite | 1 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : lymph node abscess | 1 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 4 : lymphocyte count decreased | 1 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : lymphopenia | 0 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : blood pressure increased | 0 Number of events |
| Placebo Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : rash maculo-papular | 0 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : hyponatraemia | 1 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : lymphopenia | 1 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : nausea | 0 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : urethritis | 1 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : lymph node abscess | 0 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : blood pressure increased | 1 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : C-reactive protein increased | 0 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : lymphocyte count decreased | 7 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : neutrophil count increased | 0 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : white blood cell count decreased | 0 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : blood alkaline phosphatase increased | 0 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : decreased appetite | 0 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : rash maculo-papular | 1 Number of events |
| SyB D-0701: Low Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 4 : lymphocyte count decreased | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : rash maculo-papular | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : blood alkaline phosphatase increased | 1 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : blood pressure increased | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : lymph node abscess | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : hyponatraemia | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : urethritis | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : lymphopenia | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : decreased appetite | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : nausea | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : neutrophil count increased | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : lymphocyte count decreased | 3 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 4 : lymphocyte count decreased | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : white blood cell count decreased | 0 Number of events |
| SyB D-0701: High Dose Group | Severe (Grade 3 or More) Adverse Events | Grade 3 : C-reactive protein increased | 0 Number of events |
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).
Time frame: Up to 192 hours
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Group | Skin Manifestations at Study Drug Application Site | Erythema + papules | 3 Number of events |
| Placebo Group | Skin Manifestations at Study Drug Application Site | Skin manifestations: reacted | 15 Number of events |
| Placebo Group | Skin Manifestations at Study Drug Application Site | Erythema + papules + small blisters | 0 Number of events |
| Placebo Group | Skin Manifestations at Study Drug Application Site | Clearly identifiable erythema | 12 Number of events |
| SyB D-0701: Low Dose Group | Skin Manifestations at Study Drug Application Site | Erythema + papules | 2 Number of events |
| SyB D-0701: Low Dose Group | Skin Manifestations at Study Drug Application Site | Clearly identifiable erythema | 5 Number of events |
| SyB D-0701: Low Dose Group | Skin Manifestations at Study Drug Application Site | Skin manifestations: reacted | 7 Number of events |
| SyB D-0701: Low Dose Group | Skin Manifestations at Study Drug Application Site | Erythema + papules + small blisters | 0 Number of events |
| SyB D-0701: High Dose Group | Skin Manifestations at Study Drug Application Site | Clearly identifiable erythema | 12 Number of events |
| SyB D-0701: High Dose Group | Skin Manifestations at Study Drug Application Site | Skin manifestations: reacted | 14 Number of events |
| SyB D-0701: High Dose Group | Skin Manifestations at Study Drug Application Site | Erythema + papules + small blisters | 0 Number of events |
| SyB D-0701: High Dose Group | Skin Manifestations at Study Drug Application Site | Erythema + papules | 2 Number of events |
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.
Time frame: 24-72 hours
Population: Per protocol set:~Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Group | Time to First Emesis | NA Hours |
| SyB D-0701: Low Dose Group | Time to First Emesis | NA Hours |
| SyB D-0701: High Dose Group | Time to First Emesis | NA Hours |
p-value: 0.836195% CI: [0.266, 3.172]Generalized Wilcoxon test
p-value: 0.072495% CI: [0.144, 1.237]Generalized Wilcoxon test
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.
Time frame: 24-72 hours
Population: Per protocol set:~Of all the randomized subjects, those who were compliant with the protocol were included in the per protocol set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Group | Time to First Nausea | NA Hours |
| SyB D-0701: Low Dose Group | Time to First Nausea | NA Hours |
| SyB D-0701: High Dose Group | Time to First Nausea | NA Hours |
p-value: 0.646695% CI: [0.616, 2.388]Generalized Wilcoxon test
p-value: 0.270195% CI: [0.566, 1.21]Generalized Wilcoxon test