Trial Outcomes & Findings for A Phase 2 Trial of Rebamipide Liquid to Determine the Effective Dose for Prevention of Chemoradiotherapy-induced Oral Mucositis in Patients With Head and Neck Cancer (NCT NCT02085460)

NCT ID: NCT02085460

Last Updated: 2021-10-18

Results Overview

Investigators who had undergone specific training assessed the severity of oral mucositis twice every week. To evaluate the severity of oral mucositis objectively, the clinical findings of the oral mucosa as well as functional disorders and symptomatic aspects were recorded in the Oral Mucositis Assessment Sheet by each investigator. Photographic documentation of the oral mucosa was also submitted by each investigator, 3 days before or 57 days after initiation of chemoradiotherapy, or at the time of withdrawal. The Oral Mucositis Assessment Sheets and photographic documentation were then reviewed by the Oral Mucositis Evaluation Committee to grade the severity of oral mucositis according to the CTCAE 3.0.z

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 94 participants
• Primary outcome timeframe: 77 days
• Results posted on: 2021-10-18

Participant Flow

Participant milestones

Measure	2% Rebamipide Liquid 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	4% Rebamipide Liquid 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	Placebo 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)
Overall Study STARTED	31	32	31
Overall Study COMPLETED	17	24	21
Overall Study NOT COMPLETED	14	8	10

Reasons for withdrawal

Measure	2% Rebamipide Liquid 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	4% Rebamipide Liquid 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	Placebo 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)
Overall Study Adverse Event	2	2	1
Overall Study Physician Decision	1	1	2
Overall Study Withdrawal by Subject	11	5	7

Baseline Characteristics

A Phase 2 Trial of Rebamipide Liquid to Determine the Effective Dose for Prevention of Chemoradiotherapy-induced Oral Mucositis in Patients With Head and Neck Cancer

Baseline characteristics by cohort

Measure	2% Rebamipide Liquid n=31 Participants 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	4% Rebamipide Liquid n=32 Participants 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	Placebo n=31 Participants 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	Total n=94 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants	19 Participants n=7 Participants	19 Participants n=5 Participants	55 Participants n=4 Participants
Age, Categorical >=65 years	14 Participants n=5 Participants	13 Participants n=7 Participants	12 Participants n=5 Participants	39 Participants n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	26 Participants n=7 Participants	25 Participants n=5 Participants	77 Participants n=4 Participants
Race/Ethnicity, Customized Asian	31 Participants n=5 Participants	32 Participants n=7 Participants	31 Participants n=5 Participants	94 Participants n=4 Participants
Region of Enrollment Japan	31 Participants n=5 Participants	32 Participants n=7 Participants	31 Participants n=5 Participants	94 Participants n=4 Participants

PRIMARY outcome

Timeframe: 77 days

Population: Full analysis set comprised patients who received the study drug or placebo at least once and whose efficacy data were collected immediately after beginning the treatment.

Investigators who had undergone specific training assessed the severity of oral mucositis twice every week. To evaluate the severity of oral mucositis objectively, the clinical findings of the oral mucosa as well as functional disorders and symptomatic aspects were recorded in the Oral Mucositis Assessment Sheet by each investigator. Photographic documentation of the oral mucosa was also submitted by each investigator, 3 days before or 57 days after initiation of chemoradiotherapy, or at the time of withdrawal. The Oral Mucositis Assessment Sheets and photographic documentation were then reviewed by the Oral Mucositis Evaluation Committee to grade the severity of oral mucositis according to the CTCAE 3.0.z

Outcome measures

Measure	2% Rebamipide Liquid n=31 Participants 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	4% Rebamipide Liquid n=32 Participants 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	Placebo n=31 Participants 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)
Incidence of Grade ≥3 Oral Mucositis Determined by Clinical Examination and Assessed by Central Review According to the Common Terminology Criteria of Adverse Events (CTCAE) Version 3.0.	29.0 percentage of participants	25.0 percentage of participants	38.7 percentage of participants

SECONDARY outcome

Timeframe: Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 77

Population: Full analysis set comprised patients who received the study drug or placebo at least once and whose efficacy data were collected immediately after beginning the treatment.

Day 1 was defined as the start of chemotherapy.

Outcome measures

Measure	2% Rebamipide Liquid n=31 Participants 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	4% Rebamipide Liquid n=32 Participants 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	Placebo n=31 Participants 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 1	31 participants	31 participants	31 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 29	23 participants	25 participants	23 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 36	20 participants	20 participants	19 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 43	18 participants	18 participants	16 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 50	17 participants	18 participants	15 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 77	6 participants	11 participants	8 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 8	29 participants	31 participants	30 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 15	27 participants	30 participants	29 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 22	25 participants	29 participants	23 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 57	12 participants	16 participants	13 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 64	11 participants	15 participants	11 participants
Number of Subjects Who Did Not Developed Grade ≥3 Mucositis Day 71	8 participants	13 participants	8 participants

Adverse Events

2% Rebamipide Liquid

Serious events: 5 serious events

Other events: 31 other events

Deaths: 0 deaths

4% Rebamipide Liquid

Serious events: 5 serious events

Other events: 32 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	2% Rebamipide Liquid n=31 participants at risk 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	4% Rebamipide Liquid n=32 participants at risk 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	Placebo n=31 participants at risk 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)
Cardiac disorders Sinus node dysfunction	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Dysphagia	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Nausea	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Alanine aminotransferase increased	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Blood creatinine increased	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pharyngeal cancer metastatic	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Renal and urinary disorders Renal impairment	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.4% 3/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.

Other adverse events

Measure	2% Rebamipide Liquid n=31 participants at risk 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	4% Rebamipide Liquid n=32 participants at risk 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)	Placebo n=31 participants at risk 6 times daily (The treatment started 3 days prior to the initiation of chemoradiotherapy and continued for another 77 days.)
Infections and infestations Rhinitis	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Infections and infestations Lung infection	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Blood and lymphatic system disorders Anaemia	22.6% 7/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	28.1% 9/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	32.3% 10/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Blood and lymphatic system disorders Leukopenia	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Blood and lymphatic system disorders Neutropenia	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Ear and labyrinth disorders Tinnitus	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Ear and labyrinth disorders Hearing impaired	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Stomatitis	87.1% 27/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	93.8% 30/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	96.8% 30/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Nausea	80.6% 25/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	75.0% 24/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	80.6% 25/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Constipation	67.7% 21/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	78.1% 25/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	77.4% 24/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Dry mouth	64.5% 20/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	75.0% 24/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	61.3% 19/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Vomiting	29.0% 9/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	40.6% 13/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	38.7% 12/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Diarrhoea	25.8% 8/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.5% 4/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	32.3% 10/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Dysphagia	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	15.6% 5/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	19.4% 6/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Cheilitis	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Dyspepsia	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Oral pain	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Abdominal discomfort	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Toothache	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Gastrointestinal disorders Odynophagia	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
General disorders Malaise	45.2% 14/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	37.5% 12/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	45.2% 14/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
General disorders Fatigue	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	18.8% 6/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
General disorders Oedema peripheral	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	15.6% 5/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
General disorders Pyrexia	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.5% 4/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
General disorders Face oedema	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
General disorders Infusion site extravasation	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.4% 3/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
General disorders Thirst	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
General disorders Vessel puncture site inflammation	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Hepatobiliary disorders Hepatic function abnormal	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
General disorders Hypersensitivity	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Infections and infestations Oral candidiasis	19.4% 6/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	37.5% 12/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	22.6% 7/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Infections and infestations Pharyngitis	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.4% 3/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Infections and infestations Device related infection	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Infections and infestations Influenza	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Infections and infestations Otitis externa	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Infections and infestations Staphylococcal infection	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Injury, poisoning and procedural complications Radiation skin injury	71.0% 22/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	81.2% 26/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	64.5% 20/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Injury, poisoning and procedural complications Wound complication	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Weight decreased	48.4% 15/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	37.5% 12/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	58.1% 18/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations White blood cell count decreased	38.7% 12/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	37.5% 12/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	38.7% 12/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Neutrophil count decreased	29.0% 9/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	25.0% 8/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	29.0% 9/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Lymphocyte count decreased	29.0% 9/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	28.1% 9/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	19.4% 6/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Blood creatinine increased	16.1% 5/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.5% 4/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Platelet count decreased	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.5% 4/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Alanine aminotransferase increased	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Weight increased	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Aspartate aminotransferase increased	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations C-reactive protein increased	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Investigations Gamma-glutamyltransferase increased	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Decreased appetite	67.7% 21/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	68.8% 22/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	74.2% 23/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Hyponatraemia	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.5% 4/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	22.6% 7/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Hyperkalaemia	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	15.6% 5/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	16.1% 5/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Hypokalaemia	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	16.1% 5/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Dehydration	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.4% 3/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Hypoalbuminaemia	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.5% 4/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Hypomagnesaemia	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.5% 4/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Hyperglycaemia	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Hypertriglyceridaemia	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.4% 3/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Hyperuricaemia	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Metabolism and nutrition disorders Diabetes mellitus	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Nervous system disorders Dysgeusia	71.0% 22/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	81.2% 26/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	80.6% 25/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Nervous system disorders Headache	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.1% 1/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Nervous system disorders Somnolence	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Psychiatric disorders Insomnia	19.4% 6/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	18.8% 6/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Renal and urinary disorders Renal impairment	16.1% 5/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	15.6% 5/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Respiratory, thoracic and mediastinal disorders Hiccups	35.5% 11/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	46.9% 15/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	32.3% 10/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	25.8% 8/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	28.1% 9/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	32.3% 10/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	28.1% 9/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	29.0% 9/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Respiratory, thoracic and mediastinal disorders Dysphonia	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	15.6% 5/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Respiratory, thoracic and mediastinal disorders Laryngeal pain	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	9.7% 3/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Respiratory, thoracic and mediastinal disorders Cough	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Skin and subcutaneous tissue disorders Alopecia	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	21.9% 7/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	22.6% 7/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Skin and subcutaneous tissue disorders Dermatitis	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.2% 2/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Skin and subcutaneous tissue disorders Rash	12.9% 4/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	3.2% 1/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.
Vascular disorders Hypertension	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	0.00% 0/32 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.	6.5% 2/31 • Treatment-emergent adverse events were collected from start of the study drug administration up to Day 85 Safety set comprised those who received the study drug or placebo at least once and whose safety data were collected at least once after beginning the treatment.

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: CL_OPCJ_RDA_Team@otsuka.jp

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place