Trial Outcomes & Findings for Manuka Honey in Preventing Esophagitis-Related Pain in Patients Receiving Chemotherapy and Radiation Therapy For Lung Cancer (NCT NCT01262560)

Last Updated: 2017-08-31

Results Overview

Esophagitis-related pain was measured using patient-reported pain on swallowing as assessed by the Numerical Rating Pain Scale (NRPS), an 11-point scale (0-10) in which 0 indicates no pain and 10 indicates the worst pain imaginable. Generally, scores of 1-4 indicate mild pain, scores of 5-6 indicate moderate pain, and scores of 7-10 indicate severe pain. Change was calculated by subtracting the baseline value from the 4-week value. The experimental arms (honey) were compared to the standard arm (supportive care).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

163 participants

Primary outcome timeframe

Baseline and 4 weeks from the start of treatment

Results posted on

2017-08-31

Participant Flow

Participant milestones

Participant milestones
Measure	Supportive Care Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Overall Study STARTED	53	54	56
Overall Study COMPLETED	53	53	54
Overall Study NOT COMPLETED	0	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Supportive Care Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Overall Study Protocol Violation	0	1	2

Baseline Characteristics

Manuka Honey in Preventing Esophagitis-Related Pain in Patients Receiving Chemotherapy and Radiation Therapy For Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Supportive Care n=53 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=53 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=54 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.	Total n=160 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	66 years n=7 Participants	65 years n=5 Participants	65 years n=4 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	24 Participants n=7 Participants	23 Participants n=5 Participants	74 Participants n=4 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	29 Participants n=7 Participants	31 Participants n=5 Participants	86 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 4 weeks from the start of treatment

Population: Randomized eligible patients with NRPS score at both baseline and 4 weeks.

Outcome measures

Outcome measures
Measure	Supportive Care n=40 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=41 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=38 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Change in Radiation Esophagitis-related Pain at 4 Weeks as Measured by the Numerical Rating Pain Scale for Pain on Swallowing (NRPS)	1 units on a scale Interval 0.0 to 4.0	1 units on a scale Interval 0.0 to 4.0	1 units on a scale Interval 0.0 to 4.0

SECONDARY outcome

Timeframe: Baseline, weekly during treatment, and 12 weeks from the start of treatment

Population: Eligible patients who started protocol treatment with at least 1 NRPS score completed across all time points

Esophagitis-related pain was measured using patient-reported pain on swallowing as assessed by the Numerical Rating Pain Scale (NRPS), an 11-point scale (0-10) in which 0 indicates no pain and 10 indicates the worst pain imaginable. Generally, scores of 1-4 indicate mild pain, scores of 5-6 indicate moderate pain, and scores of 7-10 indicate severe pain. Change was calculated by subtracting the baseline value from values at the later time points. The experimental arms (honey) were compared to the standard arm (supportive care).

Outcome measures

Outcome measures
Measure	Supportive Care n=49 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=50 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=51 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Radiation Esophagitis-related Pain During Treatment as Measured During Treatment and 12 Weeks by the Numerical Rating Pain Scale (NRPS) Baseline	0 units on a scale Interval 0.0 to 0.0	0 units on a scale Interval 0.0 to 0.0	0 units on a scale Interval 0.0 to 0.0
Radiation Esophagitis-related Pain During Treatment as Measured During Treatment and 12 Weeks by the Numerical Rating Pain Scale (NRPS) Week 1	0 units on a scale Interval 0.0 to 1.0	0 units on a scale Interval 0.0 to 1.0	0 units on a scale Interval 0.0 to 0.0
Radiation Esophagitis-related Pain During Treatment as Measured During Treatment and 12 Weeks by the Numerical Rating Pain Scale (NRPS) Week 2	0 units on a scale Interval 0.0 to 2.0	0 units on a scale Interval 0.0 to 1.0	0 units on a scale Interval 0.0 to 3.0
Radiation Esophagitis-related Pain During Treatment as Measured During Treatment and 12 Weeks by the Numerical Rating Pain Scale (NRPS) Week 3	0 units on a scale Interval 0.0 to 4.0	1 units on a scale Interval 0.0 to 4.0	1 units on a scale Interval 0.0 to 3.0
Radiation Esophagitis-related Pain During Treatment as Measured During Treatment and 12 Weeks by the Numerical Rating Pain Scale (NRPS) 4 weeks	1 units on a scale Interval 0.0 to 4.0	1 units on a scale Interval 0.0 to 4.0	2 units on a scale Interval 0.0 to 5.0
Radiation Esophagitis-related Pain During Treatment as Measured During Treatment and 12 Weeks by the Numerical Rating Pain Scale (NRPS) Week 5	2.5 units on a scale Interval 0.0 to 4.5	2 units on a scale Interval 0.0 to 5.0	3 units on a scale Interval 0.0 to 6.0
Radiation Esophagitis-related Pain During Treatment as Measured During Treatment and 12 Weeks by the Numerical Rating Pain Scale (NRPS) End of RT	3 units on a scale Interval 0.0 to 5.5	3 units on a scale Interval 0.0 to 6.0	4 units on a scale Interval 0.0 to 6.0
Radiation Esophagitis-related Pain During Treatment as Measured During Treatment and 12 Weeks by the Numerical Rating Pain Scale (NRPS) Week 12	0 units on a scale Interval 0.0 to 2.0	0 units on a scale Interval 0.0 to 2.5	0 units on a scale Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: Weekly during treatment and 12 weeks from the start of treatment

Population: Randomized eligible patients who received protocol treatment with at least one dysphagia score completed across all time points.

Dysphagia, as reported by the patient, was measured by the patient swallowing diary. Swallowing score has increasing severity 1-5, where 1 = "none" and 5 = "cannot swallow liquids".

Outcome measures

Outcome measures
Measure	Supportive Care n=46 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=50 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=59 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Dysphagia Via Daily Patient Log Baseline	1 units on a scale Interval 1.0 to 1.0	1 units on a scale Interval 1.0 to 1.0	1 units on a scale Interval 1.0 to 1.0
Dysphagia Via Daily Patient Log Week 1	1 units on a scale Interval 1.0 to 1.14	1 units on a scale Interval 1.0 to 1.0	1 units on a scale Interval 1.0 to 1.29
Dysphagia Via Daily Patient Log Week 2	1 units on a scale Interval 1.0 to 1.57	1 units on a scale Interval 1.0 to 1.43	1.07 units on a scale Interval 1.0 to 2.0
Dysphagia Via Daily Patient Log Week 3	1.36 units on a scale Interval 1.0 to 2.43	2 units on a scale Interval 1.0 to 2.14	1.86 units on a scale Interval 1.0 to 2.86
Dysphagia Via Daily Patient Log Week 4	1.86 units on a scale Interval 1.0 to 2.86	2 units on a scale Interval 1.0 to 2.57	2.07 units on a scale Interval 1.15 to 3.0
Dysphagia Via Daily Patient Log Week 5	2.5 units on a scale Interval 1.07 to 3.0	2 units on a scale Interval 1.0 to 3.0	2.71 units on a scale Interval 2.0 to 3.0
Dysphagia Via Daily Patient Log End of RT	2 units on a scale Interval 1.0 to 3.0	2.86 units on a scale Interval 1.71 to 3.0	3 units on a scale Interval 2.86 to 3.71
Dysphagia Via Daily Patient Log Week 12	1 units on a scale Interval 1.0 to 2.0	1 units on a scale Interval 1.0 to 3.0	1 units on a scale Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: Baseline, 4 and 12 weeks from the start of treatment

Population: Randomized eligible patients who received protocol treatment with at least 1 EORTC score completed across all time points.

The pain symptom subscale (2 items) evaluated pain and the global score (30 items) evaluated quality of life. Each ranges from 0-100 with lower scores indicating lesser burden and improved symptoms or quality of life.

Outcome measures

Outcome measures
Measure	Supportive Care n=48 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=50 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=52 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Quality of Life and Pain, as Measured by the EORTC QLQ-30 Global QOL Score and Pain Symptom Subscale at 4 and 12 Weeks Baseline - Global health status	66.67 units on a scale Interval 54.17 to 83.33	66.67 units on a scale Interval 50.0 to 83.33	66.67 units on a scale Interval 50.0 to 83.33
Quality of Life and Pain, as Measured by the EORTC QLQ-30 Global QOL Score and Pain Symptom Subscale at 4 and 12 Weeks Baseline - Pain	16.67 units on a scale Interval 0.0 to 41.67	16.67 units on a scale Interval 0.0 to 33.33	16.67 units on a scale Interval 0.0 to 50.0
Quality of Life and Pain, as Measured by the EORTC QLQ-30 Global QOL Score and Pain Symptom Subscale at 4 and 12 Weeks Week 4 - Global health status	66.67 units on a scale Interval 50.0 to 75.0	62.50 units on a scale Interval 45.83 to 75.0	66.67 units on a scale Interval 50.0 to 75.0
Quality of Life and Pain, as Measured by the EORTC QLQ-30 Global QOL Score and Pain Symptom Subscale at 4 and 12 Weeks Week 4 - Pain	25.00 units on a scale Interval 0.0 to 33.33	16.67 units on a scale Interval 0.0 to 50.0	33.33 units on a scale Interval 0.0 to 50.0
Quality of Life and Pain, as Measured by the EORTC QLQ-30 Global QOL Score and Pain Symptom Subscale at 4 and 12 Weeks Week 12 - Global health status	66.67 units on a scale Interval 50.0 to 83.33	58.33 units on a scale Interval 41.67 to 83.33	66.67 units on a scale Interval 41.67 to 83.33
Quality of Life and Pain, as Measured by the EORTC QLQ-30 Global QOL Score and Pain Symptom Subscale at 4 and 12 Weeks Week 12 - Pain	0.00 units on a scale Interval 0.0 to 33.33	16.67 units on a scale Interval 0.0 to 33.33	16.67 units on a scale Interval 0.0 to 33.33

SECONDARY outcome

Timeframe: Up to 12 weeks from the start of treatment

Population: Randomized eligible patients who started protocol treatment

Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. For esophagitis specifically, Grade 3 criteria includes severely altered eating/swallowing, tube feeding, total parenteral nutrition (TPN) or hospitalization indicated. Grade 4 criteria include life-threatening consequences, urgent operative intervention indicated.

Outcome measures

Outcome measures
Measure	Supportive Care n=48 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=50 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=50 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Percentage of Participants With Radiation Esophagitis Grade 3-4 (CTCAE v. 4)	12.5 percentage of participants Interval 3.1 to 21.9	2.0 percentage of participants Interval 0.0 to 5.9	6.0 percentage of participants Interval 0.0 to 12.6

SECONDARY outcome

Timeframe: Baseline and 4 weeks from the start of treatment

Population: Randomized eligible patients with weight at both baseline and 4 weeks.

Outcome measures

Outcome measures
Measure	Supportive Care n=50 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=51 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=51 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Percent Change in Weight From Baseline to 4 Weeks	-2.22 percentage of baseline value Interval -7.26 to 14.79	-0.62 percentage of baseline value Interval -1.57 to 2.83	-2.64 percentage of baseline value Interval -4.53 to 5.64

SECONDARY outcome

Timeframe: Baseline and 4 weeks from the start of treatment

Population: Randomized eligible patients with serum prealbumin at baseline and 4 weeks.

Outcome measures

Outcome measures
Measure	Supportive Care n=50 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=51 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=51 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Nutritional Status (Change in Serum Prealbumin Levels From Baseline to 4 Weeks)	-3.34 mg/dl Interval -9.46 to 17.98	5.25 mg/dl Interval -6.42 to 34.7	0.17 mg/dl Interval -1.94 to 6.28

SECONDARY outcome

Timeframe: Baseline, 4 weeks, end of radiation treatment, and 12 weeks from the start of treatment

Population: Randomized eligible patients with opioid use information at at least one time point.

The percentage of patients using opioid analgesics is reported. Use of opioid analgesics was assessed for a 24-hour period before completing the assessment. Patients with at least one reported administration of opioid analgesic were considered to have received opioid analgesics.

Outcome measures

Outcome measures
Measure	Supportive Care n=53 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=53 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=54 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Percentage of Patients Using Opioids Week 12	32.6 percentage of participants	17.4 percentage of participants	18.2 percentage of participants
Percentage of Patients Using Opioids Baseline	13.2 percentage of participants	9.4 percentage of participants	13.0 percentage of participants
Percentage of Patients Using Opioids Week 4	37.0 percentage of participants	14.3 percentage of participants	29.2 percentage of participants
Percentage of Patients Using Opioids End of RT	46.5 percentage of participants	36.2 percentage of participants	43.2 percentage of participants

SECONDARY outcome

Timeframe: Until 12 weeks from the start of treatment

Population: Randomized eligible patients who started protocol treatment.

Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

Outcome measures

Outcome measures
Measure	Supportive Care n=48 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=50 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=50 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Adverse Events Associated With Manuka Honey Using CTCAE v4.0 Grade 3	10.4 percentage of patients	8.0 percentage of patients	8.0 percentage of patients
Adverse Events Associated With Manuka Honey Using CTCAE v4.0 Grade 1	6.3 percentage of patients	16.0 percentage of patients	12.0 percentage of patients
Adverse Events Associated With Manuka Honey Using CTCAE v4.0 Grade 2	20.8 percentage of patients	26.0 percentage of patients	18.0 percentage of patients
Adverse Events Associated With Manuka Honey Using CTCAE v4.0 Grade 4	2.1 percentage of patients	0.0 percentage of patients	2.0 percentage of patients
Adverse Events Associated With Manuka Honey Using CTCAE v4.0 Grade 5	0.0 percentage of patients	0.0 percentage of patients	0.0 percentage of patients

SECONDARY outcome

Timeframe: Baseline and 4 weeks from the start of treatment

Population: Randomized eligible patients who started treatment with measure at both baseline and 4 weeks.

Change from baseline to four weeks in patient-reported difficulty in swallowing via the PRO-CTCAE. PRO-CTCAE is an item bank consisting of individual items to assess adverse symptom events from the patient perspective. There are 78 symptoms included in the survey but the primary item of interest assesses difficulty swallowing. For each AE in the PRO-CTCAE, between 1 and 3 items are included to assess the frequency, severity, and/or interference with activities related to that AE. Frequency questions have responses ranging from never, which is scored as a 0, to almost constantly, which is scored as a 4. Severity questions have responses ranging from none, which is scored as a 0, to very severe, which is scored as a 4. Interference questions have responses ranging from not at all, which is scored as a 0, to very much, which is scored as a 4. Difficulty in swallowing only has a severity question.

Outcome measures

Outcome measures
Measure	Supportive Care n=36 Participants Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=33 Participants Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=35 Participants Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Patient Reported Difficulty in Swallowing Associated With Manuka Honey Using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	1 units on a scale Interval 0.0 to 2.0	1 units on a scale Interval 0.0 to 2.0	1 units on a scale Interval 0.0 to 2.0

Adverse Events

Supportive Care

Serious events: 16 serious events

Other events: 37 other events

Deaths: 0 deaths

Liquid Manuka Honey

Serious events: 13 serious events

Other events: 46 other events

Deaths: 0 deaths

Lozenge Manuka Honey

Serious events: 9 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	Supportive Care n=48 participants at risk Standard supportive care for esophagitis-related pain as needed during concurrent chemotherapy and radiation treatment.	Liquid Manuka Honey n=50 participants at risk Manuka honey in liquid form during concurrent chemotherapy and radiation treatment.	Lozenge Manuka Honey n=50 participants at risk Manuka honey in lozenge form during concurrent chemotherapy and radiation treatment.
Blood and lymphatic system disorders Anemia	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.0% 2/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Blood and lymphatic system disorders Febrile neutropenia	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	6.0% 3/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Cardiac disorders Atrial fibrillation	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Cardiac disorders Cardiac arrest	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Cardiac disorders Myocardial infarction	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Abdominal pain	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Colonic perforation	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Diarrhea	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Dysphagia	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Esophagitis	10.4% 5/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.0% 2/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Gastrointestinal disorders - Other	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Nausea	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Small intestinal obstruction	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Gastrointestinal disorders Vomiting	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Fatigue	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
General disorders Infusion related reaction	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Infections and infestations Lung infection	4.2% 2/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.0% 2/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Infections and infestations Sepsis	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Infections and infestations Skin infection	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Infections and infestations Urinary tract infection	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.0% 2/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Aspartate aminotransferase increased	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Neutrophil count decreased	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.0% 2/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.0% 2/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Platelet count decreased	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.0% 2/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations Weight loss	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Investigations White blood cell decreased	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.0% 2/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.0% 2/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Metabolism and nutrition disorders Anorexia	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Metabolism and nutrition disorders Dehydration	6.2% 3/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	4.0% 2/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Metabolism and nutrition disorders Hypokalemia	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Nervous system disorders Nervous system disorders - Other	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Psychiatric disorders Anxiety	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Renal and urinary disorders Acute kidney injury	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Cough	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	6.0% 3/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Respiratory, thoracic and mediastinal disorders Laryngeal stenosis	0.00% 0/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Vascular disorders Hypotension	2.1% 1/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	2.0% 1/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Vascular disorders Thromboembolic event	4.2% 2/48 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.	0.00% 0/50 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.