Trial Outcomes & Findings for CHAIROS Study A Study of MabThera/Rituxan (Rituximab) Maintenance Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL) Naive to Chemotherapy (NCT NCT02013817)

NCT ID: NCT02013817

Last Updated: 2017-08-18

Results Overview

Best clinical response was determined according to the National Cancer Institute (NCI) Clinical and Clinical plus (+) Radiological evaluations by central response assessment. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of chronic lymphocytic lymphoma (CLL) with additional computerized tomography (CT) scan evaluation of lymphadenopathy. Per NCI guidelines, CR requires all of the following criteria at least 2 months after the last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/constitutional symptoms; neutrophils greater than (\>)1500 per microliter (/µL), platelets (PL) \>100,000/µL, hemoglobin (Hb) \>11.0 grams per deciliter (g/dL), lymphocytes (LC) (less than) \<4000/µL, bone marrow (BM) sample must be normocellular for age, \<30% LC.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

Weeks 1, 5, 9, 12, 13, 17, 21 and 24

Results posted on

2017-08-18

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab, Fludarabine, Cyclophosphamide Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 milligrams per square meter (mg/m\^2) intravenously (IV) and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Overall Study STARTED	43
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab, Fludarabine, Cyclophosphamide Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 milligrams per square meter (mg/m\^2) intravenously (IV) and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Overall Study Adverse Event	12
Overall Study Withdrawal by Subject	4
Overall Study Death	2
Overall Study Other	9

Baseline Characteristics

CHAIROS Study A Study of MabThera/Rituxan (Rituximab) Maintenance Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL) Naive to Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab, Fludarabine, Cyclophosphamide n=43 Participants Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Age, Continuous	61.0 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: Weeks 1, 5, 9, 12, 13, 17, 21 and 24

Population: ITT Population

Outcome measures

Outcome measures
Measure	Rituximab, Fludarabine, Cyclophosphamide n=38 Participants Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Percentage of Participants With a Best Clinical Response of Clinical Remission (CR) NCI Clinical	73.7 percentage of participants Interval 56.9 to 86.6
Percentage of Participants With a Best Clinical Response of Clinical Remission (CR) NCI Clinical (including CRu, CRi)	94.7 percentage of participants Interval 82.3 to 99.4
Percentage of Participants With a Best Clinical Response of Clinical Remission (CR) NCI Clinical + Radiological	63.2 percentage of participants Interval 46.0 to 78.2
Percentage of Participants With a Best Clinical Response of Clinical Remission (CR) NCI Clinical + Radiological (including CRu, CRi)	78.9 percentage of participants Interval 62.7 to 90.4

SECONDARY outcome

Timeframe: Weeks 12 and 24 and at Final Staging (Week 4 after last maintenance dose)

Population: ITT Population

Best clinical response was determined according to the NCI clinical evaluation and through radiological assessment. CR, CRi, CRu, partial remission (PR), partial remission with toxicity associated (PRTox), progressive disease (PD), and stable disease (SD) were evaluated. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of CLL with additional CT scan evaluation of lymphadenopathy during the treatment period (Radiological). Response assessment for interim (Week 12), end of induction (Week 24) and at Final Staging (4 weeks after last maintenance dose). Last observation carried forward (LOCF) method was used for missing data. Percentages are based on the number of nonmissing observations within each stratum.

Outcome measures

Outcome measures
Measure	Rituximab, Fludarabine, Cyclophosphamide n=43 Participants Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) CR, Week 12	41.9 percentage of participants Interval 27.0 to 57.9
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) CRu, Week 12	16.3 percentage of participants Interval 6.8 to 30.7
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) CRi, Week 12	16.3 percentage of participants Interval 6.8 to 30.7
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) PR, Week 12	11.6 percentage of participants Interval 3.9 to 25.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) PRTox, Week 12	2.3 percentage of participants Interval 0.1 to 12.3
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) SD, Week 12	0.0 percentage of participants Interval 0.0 to 8.2
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) PD, Week 12	0.0 percentage of participants Interval 0.0 to 8.2
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) Not evaluable, Week 12	11.6 percentage of participants Interval 3.9 to 25.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) CR, Week 24	30.2 percentage of participants Interval 17.2 to 46.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) CRu, Week 24	11.6 percentage of participants Interval 3.9 to 25.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) CRi, Week 24	37.2 percentage of participants Interval 23.0 to 53.3
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) PR, Week 24	9.3 percentage of participants Interval 2.6 to 22.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) PRTox, Week 24	0.0 percentage of participants Interval 0.0 to 8.2
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) SD, Week 24	0.0 percentage of participants Interval 0.0 to 8.2
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) PD, Week 24	0.0 percentage of participants Interval 0.0 to 8.2
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) Not evaluable, Week 24	11.6 percentage of participants Interval 3.9 to 25.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) CR, Final staging	60.5 percentage of participants Interval 44.4 to 75.0
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) CRu, Final staging	7.0 percentage of participants Interval 1.5 to 19.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) CRi, Final staging	11.6 percentage of participants Interval 3.9 to 25.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) PR, Final staging	7.0 percentage of participants Interval 1.5 to 19.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) PRTox, Final staging	0.0 percentage of participants Interval 0.0 to 8.2
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) SD, Final staging	0.0 percentage of participants Interval 0.0 to 8.2
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) PD, Final staging	2.3 percentage of participants Interval 0.1 to 12.3
Percentage of Participants With the Best Clinical Response by Visit (Clinical Assessment) Not evaluable, Final staging	11.6 percentage of participants Interval 3.9 to 25.1

SECONDARY outcome

Timeframe: Weeks 12 and 24 and at Final Staging (Week 4 after last maintenance dose)

Population: ITT Population

Best clinical response was determined according to the NCI clinical evaluation and through radiological assessment. CR, CRi, CRu, PR, PRTox, PD, and SD were evaluated. Assessment of response was performed according to the NCI revised guidelines for the diagnosis and treatment of CLL with additional CT scan evaluation of lymphadenopathy during the treatment period (Radiological). Response assessment for interim (Week 12), end of induction (Week 24) and at Final Staging (4 weeks after last maintenance dose). LOCF method was used for missing data. Percentages are based on the number of nonmissing observations within each stratum.

Outcome measures

Outcome measures
Measure	Rituximab, Fludarabine, Cyclophosphamide n=43 Participants Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) CR, Week 12	30.2 percentage of participants Interval 17.2 to 46.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) CRu, Week 12	4.7 percentage of participants Interval 0.6 to 15.8
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) CRi, Week 12	7.0 percentage of participants Interval 1.5 to 19.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) PR, Week 12	30.2 percentage of participants Interval 17.2 to 46.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) PRTox, Week 12	9.3 percentage of participants Interval 2.6 to 22.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) SD, Week 124	7.0 percentage of participants Interval 1.5 to 19.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) PD, Week 12	0.0 percentage of participants Interval 0.0 to 8.2
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) Not evaluable, Week 12	11.6 percentage of participants Interval 3.9 to 25.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) CR, Week 24	23.3 percentage of participants Interval 11.8 to 38.6
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) CRu, Week 24	7.0 percentage of participants Interval 1.5 to 19.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) CRi, Week 24	30.2 percentage of participants Interval 17.2 to 46.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) PR, Week 24	14.0 percentage of participants Interval 5.3 to 27.9
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) PRTox, Week 24	7.0 percentage of participants Interval 1.5 to 19.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) SD, Week 24	7.0 percentage of participants Interval 1.5 to 19.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) PD, Week 24	0.0 percentage of participants Interval 0.0 to 8.2
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) Not evaluable, Week 24	11.6 percentage of participants Interval 3.9 to 25.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) CR, Final staging	48.8 percentage of participants Interval 33.3 to 64.5
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) CRu, Final staging	7.0 percentage of participants Interval 1.5 to 19.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) CRi, Final staging	7.0 percentage of participants Interval 1.5 to 19.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) PR, Final staging	11.6 percentage of participants Interval 3.9 to 25.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) PRTox, Final staging	2.3 percentage of participants Interval 0.1 to 12.3
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) SD, Final staging	2.3 percentage of participants Interval 0.1 to 12.3
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) PD, Final staging	9.3 percentage of participants Interval 2.6 to 22.1
Percentage of Participants With the Best Clinical Response by Visit (Clinical + Radiological Assessment) Not evaluable, Final staging	11.6 percentage of participants Interval 3.9 to 25.1

SECONDARY outcome

Timeframe: Weeks 1, 5, 9, 12, 13, 17, 21 and 24 and every 8 weeks for 64 Weeks and every 6 months

Time to next treatment was calculated as the number of days from either discontinuation of the study drug or the administration of the last dose, until the participants needed next treatment.

Outcome measures

Outcome measures
Measure	Rituximab, Fludarabine, Cyclophosphamide n=43 Participants Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Time to Next Treatment - Percentage of Participants With an Event	37.2 percentage of participants

SECONDARY outcome

Timeframe: Weeks 1, 5, 9, 12, 13, 17, 21 and 24 and every 8 weeks for 64 Weeks and every 6 months

Time to next treatment was calculated as the number of days from either discontinuation of the study drug or the administration of the last dose, until the participants needed next treatment.

Outcome measures

Outcome measures
Measure	Rituximab, Fludarabine, Cyclophosphamide n=43 Participants Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Time to Next Treatment - Time to Event	423.3 days Standard Deviation 398.5

SECONDARY outcome

Timeframe: Day 1 of Cycles 1, 2, 3, 4, 5, and 6 to 28 days after the last trial medication.

Population: ITT population

AEs were recorded from the date of first medication administration until 28 days after the last trial medication.

Outcome measures

Outcome measures
Measure	Rituximab, Fludarabine, Cyclophosphamide n=43 Participants Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Percentage of Participants With Adverse Events (AEs) Severe AE	76.7 percentage of participants
Percentage of Participants With Adverse Events (AEs) Any AE	100 percentage of participants
Percentage of Participants With Adverse Events (AEs) Related AE	93.0 percentage of participants
Percentage of Participants With Adverse Events (AEs) SAE	62.8 percentage of participants
Percentage of Participants With Adverse Events (AEs) Pregnancy	0.0 percentage of participants

Adverse Events

Rituximab, Fludarabine, Cyclophosphamide

Serious events: 30 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab, Fludarabine, Cyclophosphamide n=43 participants at risk Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Infections and infestations Bronchitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Cytomegalovirus infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Pharyngitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Pneumonia	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Pneumonia primary atypical	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Postoperative infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Psoas abscess	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Respiratory tract infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Urninary tract infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Viral infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Pyrexia	11.6% 5/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Chest pain	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Drug intolerance	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders General physical health deterioration	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Abdominal pain	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Aphthous stomatitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Colonic polyp	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Diarrhoea	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Stomatitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Blood and lymphatic system disorders Leukopenia	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Blood and lymphatic system disorders Anaemia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Blood and lymphatic system disorders Febrile neutropenia	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Arthralgia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Back pain	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Vascular disorders Capillary leak syndrome	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Osteitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Injury, poisoning and procedural complications Extradural haematoma	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Injury, poisoning and procedural complications Femoral neck fracture	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Injury, poisoning and procedural complications Skull fracture	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour lysis syndrome	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Cerebrovascular accident	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Subarachnoid haemorrhage	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Renal and urinary disorders Renal colic	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Renal and urinary disorders Urinary retention	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Actinic keratosis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Drug eruption	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Respiratory, thoracic and mediastinal disorders Bronchospasm	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Surgical and medical procedures Cataract operation	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Surgical and medical procedures Prostatic operation	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Hepatobiliary disorders Bile duct stone	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Immune system disorders Anaphylactic reaction	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Investigations Ateriogram coronary	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Metabolism and nutrition disorders Hyperglycaemia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Encephalitis herpes	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Febrile infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Sepsis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Tuberculosis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.

Other adverse events

Other adverse events
Measure	Rituximab, Fludarabine, Cyclophosphamide n=43 participants at risk Induction Phase Cycle 1 (4-week cycle): Participants received fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 and rituximab 375 mg/m\^2 IV on Day 4. Induction Phase Cycles 2 and 3 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV and cyclophosphamide 250 mg/m\^2 IV on Days 1-3 Induction Phase Cycles 4 to 6 (4-week cycles): Participants received rituximab 500 mg/m\^2 IV on Day 1 and fludarabine 25 mg/m\^2 IV on Days 1-5. Maintenance Phase (Cycles 1-8; 12-week cycles): 8 weeks after the end of the last induction cycle, participants received maintenance therapy with rituximab 375 mg/m\^2, IV once every 12 weeks for a total of 8 infusions (maximum 2 years).
Blood and lymphatic system disorders Leukopenia	46.5% 20/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Blood and lymphatic system disorders Neutropenia	53.5% 23/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Blood and lymphatic system disorders Thrombocytopenia	41.9% 18/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Blood and lymphatic system disorders Anaemia	30.2% 13/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Blood and lymphatic system disorders Lymphopenia	32.6% 14/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Blood and lymphatic system disorders Haemolysis	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Blood and lymphatic system disorders Febrile neutropenia	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Blood and lymphatic system disorders Pancytopenia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Nasopharyngitis	18.6% 8/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Rhinitis	14.0% 6/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Urinary tract infection	9.3% 4/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Influenza	9.3% 4/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Herpes simplex	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Respiratory tract infection	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Sinusitis	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Fungal infection	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Infection	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Oral candidiasis	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Bronchitis bacterial	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Febrile infection	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Fungal rash	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Gastroenteritis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Gastrointestinal infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Herpes virus infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Herpes zoster	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Laryngitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Localised infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Lymphangitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Omphalitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Oral fungal infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Perianal abscess	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Postoperative infection	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Tooth abscess	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Viral pharyngitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Pyrexia	16.3% 7/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Fatigue	18.6% 8/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Oedema peripheral	9.3% 4/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Chest pain	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Chills	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Influenza like illness	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Pain	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Mucosal inflammation	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
General disorders Oedema	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Nausea	32.6% 14/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Diarrhoea	23.3% 10/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Abdominal pain	9.3% 4/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Constipation	9.3% 4/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Abdominal pain upper	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Vomiting	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Gastritis	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Abdominal distension	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Bowel movement irregularity	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Dyspepsia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Flatulence	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Paraesthesia oral	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Proctalgia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Subileus	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Arthralgia	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Back pain	9.3% 4/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Bone pain	9.3% 4/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Neck pain	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Arthritis	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Muscle spasms	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Osteoporosis	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Pain in extremity	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Exostosis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Myalgia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Osteoarthritis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Musculoskeletal and connective tissue disorders Pain in jaw	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Respiratory, thoracic and mediastinal disorders Cough	32.6% 14/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Respiratory, thoracic and mediastinal disorders Dysphonia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Respiratory, thoracic and mediastinal disorders Dysphonia exertional	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Respiratory, thoracic and mediastinal disorders Lung disorder	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Ear and labyrinth disorders Vertigo	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Ear and labyrinth disorders Hypoacusis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Ear and labyrinth disorders Tinnitus	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Hepatobiliary disorders Hepatitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Hepatobiliary disorders Hyperbilirubinaemia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Reproductive system and breast disorders Menopausal symptoms	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Reproductive system and breast disorders Oedema genital	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Reproductive system and breast disorders Testicular pain	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Cardiac disorders Angina pectoris	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Cardiac disorders Arteriosclerosis coronary artery	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Cardiac disorders Palpitations	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Endocrine disorders Hyperthyroidism	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Endocrine disorders Hypothyroidism	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Eye disorders Visual acuity reduced	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Psychiatric disorders Burnout syndrome	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Rash	16.3% 7/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Actinic keratosis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Hyperkeratosis	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Rash maculo-papular	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Rash pruritic	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Alopecia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Dermatitis acneiform	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Eczema	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Erythema	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Night sweats	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Pemphigoid	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Subcutaneous nodule	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Skin and subcutaneous tissue disorders Urticaria	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Dizziness	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Headache	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Sciatica	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Carotid artery stenosis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Carpal tunnel syndrome	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Convulsions local	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Dysaesthesia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Neuropathy	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Polyneuropathy	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Nervous system disorders Sensory loss	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Vascular disorders Hypertension	7.0% 3/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Vascular disorders Circulatory collapse	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Vascular disorders Hot flush	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Vascular disorders Hypotension	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Vascular disorders Vein pain	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Vascular disorders Venous insufficiency	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Metabolism and nutrition disorders Hypokalaemia	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Metabolism and nutrition disorders Anorexia	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Metabolism and nutrition disorders Iron deficiency	4.7% 2/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Metabolism and nutrition disorders Lactose intolerance	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Immune system disorders Drug hypersensitivity	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Immune system disorders Food allergy	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Immune system disorders Hypersensitivity	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Injury, poisoning and procedural complications Neck injury	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Injury, poisoning and procedural complications Thermal burn	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Injury, poisoning and procedural complications Thoracic vertebral fracture	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Investigations C-reactive protein increased	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Investigations Neutrophil count decreased	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Investigations Weight decreased	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Investigations White blood cell count decreased	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Renal and urinary disorders Dysuria	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Renal and urinary disorders Renal pain	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Renal and urinary disorders Urinary tract pain	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Gastrointestinal disorders Abdominal discomfort	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Renal and urinary disorders Micturition disorder	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Psychiatric disorders Depression	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Bronchitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.
Infections and infestations Pharyngitis	2.3% 1/43 • Adverse events (AEs) were recorded from the date of first medication administration until 28 days after the last trial medication. Number and percentage of subjects with at least one AE/SAE starting during study until within 28 days after the last trial medication by stem organ class and preferred term.

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER