Trial Outcomes & Findings for Subcutaneous Alemtuzumab (CAMPATH®, MabCampath®) in Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia (NCT NCT00328198)

NCT ID: NCT00328198

Last Updated: 2014-03-13

Results Overview

Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The best response observed during the study is summarized. Response categories include Complete Response (CR) with normal physical exam, marrow cells and blood values, Partial Response (PR) with a \>= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam, Stable Disease (SD) without significant progression from baseline, or Progressive Disease (PD) with increased size/number of nodes, size of liver or spleen, increase in lymphocytes, aggressive histology.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 86 participants
• Primary outcome timeframe: up to 44 weeks
• Results posted on: 2014-03-13

Participant Flow

109 patients screened and 86 enrolled and treated.

Participant milestones

Measure	Alemtuzumab 30mg Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Treatment STARTED	86
Treatment COMPLETED	48
Treatment NOT COMPLETED	38
Follow-up STARTED	78
Follow-up COMPLETED	43
Follow-up NOT COMPLETED	35

Reasons for withdrawal

Measure	Alemtuzumab 30mg Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Treatment Adverse Event	21
Treatment Death	1
Treatment Physician Decision	5
Treatment Withdrawal by Subject	5
Treatment Evidence of disease progression	2
Treatment Non-compliance	1
Treatment Confirmed complete response, MRD -	3
Follow-up Lost to Follow-up	4
Follow-up Death	31

Baseline Characteristics

Subcutaneous Alemtuzumab (CAMPATH®, MabCampath®) in Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Measure	Alemtuzumab 30mg n=86 Participants Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Age, Continuous	65.32 years STANDARD_DEVIATION 9.035 • n=93 Participants
Sex: Female, Male Female	29 Participants n=93 Participants
Sex: Female, Male Male	57 Participants n=93 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=93 Participants
Race/Ethnicity, Customized Asian	1 participants n=93 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=93 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=93 Participants
Race/Ethnicity, Customized White	82 participants n=93 Participants
Race/Ethnicity, Customized Other	1 participants n=93 Participants
Current Rai Stage Rai Stage 0	7 participants n=93 Participants
Current Rai Stage Rai Stage I	10 participants n=93 Participants
Current Rai Stage Rai Stage II	22 participants n=93 Participants
Current Rai Stage Rai Stage III	7 participants n=93 Participants
Current Rai Stage Rai Stage IV	40 participants n=93 Participants
Current Binet Stage Stage A	20 participants n=93 Participants
Current Binet Stage Stage B	22 participants n=93 Participants
Current Binet Stage Stage C	44 participants n=93 Participants
World Health Organization (WHO) Performance 0	55 participants n=93 Participants
World Health Organization (WHO) Performance 1	28 participants n=93 Participants
World Health Organization (WHO) Performance 2	3 participants n=93 Participants

PRIMARY outcome

Timeframe: up to 44 weeks

Population: Full analysis set

Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The best response observed during the study is summarized. Response categories include Complete Response (CR) with normal physical exam, marrow cells and blood values, Partial Response (PR) with a >= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam, Stable Disease (SD) without significant progression from baseline, or Progressive Disease (PD) with increased size/number of nodes, size of liver or spleen, increase in lymphocytes, aggressive histology.

Outcome measures

Measure	Alemtuzumab 30mg n=86 Participants Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP) Overall response (CR+PR)	37 participants
Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP) Complete response (CR)	5 participants
Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP) Partial response (PR)	32 participants
Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP) Stable disease (SD)	24 participants
Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP) Progressive disease (PD)	4 participants
Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP) Not Evaluable (NE)	21 participants

PRIMARY outcome

Timeframe: up to 44 weeks

Population: Full analysis set. 95% confidence interval calculated using exact binomial method.

Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The percentage of participants whose best response observed during the study was either a Complete Response (CR) or a Partial Response (PR). Overall Response (OR) = CR + PR. A Complete Response (CR) exhibits a normal physical exam, marrow cells and blood values. A Partial Response (PR) has a >= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam.

Outcome measures

Measure	Alemtuzumab 30mg n=86 Participants Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Percentage of Participants Who Had an Overall Response (OR) as Determined by the Independent Response Review Panel (IRRP)	43.0 percentage of participants Interval 32.4 to 54.2

SECONDARY outcome

Timeframe: up to 5 years

Population: Full analysis set

Progression-free survival was defined as the number of days from the date of first treatment to the date of first objective documentation of progressive disease (PD) as determined by the IRRP, or death due to any cause. Results are expressed in months.

Progressive Disease (PD) was defined as an increase in size/number of nodes, size of liver or spleen, increase in lymphocytes, or aggressive histology.

Outcome measures

Measure	Alemtuzumab 30mg n=86 Participants Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Kaplan-Meier Estimates of Progression Free Survival as Determined by the Independent Response Review Panel (IRRP)	12.43 months Interval 9.934 to 14.375

SECONDARY outcome

Timeframe: up to 5 years

Population: Participants who had a complete response or a partial response

Duration of response was analyzed for participants who achieved a complete response (CR) or partial response (PR) and was defined as the number of days from the first date of documented response to the date of progressive disease (PD) as determined by IRRP or death due to any cause. Results are stated in months.

Progressive Disease (PD) was defined as an increase in size/number of nodes, size of liver or spleen, increase in lymphocytes, or aggressive histology.

Outcome measures

Measure	Alemtuzumab 30mg n=37 Participants Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Kaplan-Meier Estimates of Duration of Response as Determined by the Independent Response Review Panel (IRRP)	11.09 months Interval 9.013 to 14.572

SECONDARY outcome

Timeframe: up to 5 years

Population: Full analysis set

Overall survival was defined as the time in days from the date of first treatment to the date of death due to any cause for all participants. Results are stated in months.

Outcome measures

Measure	Alemtuzumab 30mg n=86 Participants Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Kaplan-Meier Estimates of Overall Survival	38.29 months Interval 30.099 to values were not calculable since there were not enough events for the statistical estimation, ie, few participants died

SECONDARY outcome

Timeframe: 44 weeks

Population: Full analysis set

MRD negativity represents a very positive response outcome. MRD negativity in this report was defined by the absence of tumor cells in bone marrow, using 4-color flow cytometry. All patients are evaluated for treatment response based on National Cancer Institute Working Group (NCIWG) criteria. Of patients who have achieved a clinical complete response (CR) or partial response (PR) that met National Cancer Institute Working Group (NCIWG) criteria of CR except blood recovery, a bone marrow sample was taken for flow cytometry measure of MRD negativity.

Outcome measures

Measure	Alemtuzumab 30mg n=86 Participants Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Participants With a Minimal Residual Disease (MRD) Status of Negative	4 participants

SECONDARY outcome

Timeframe: up to 18 weeks of treatment plus 45 days

Population: Full analysis set

Number of participants with treatment-emergent adverse events (TEAEs). AEs were graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and were assessed for relatedness to study treatment (5 point scale from 'not related' to 'definitely related') and severity (5 point scale with grade 5 being most severe). Categories reported include participant counts for treatment-emergent AEs, injection site reactions, AEs for infections, serious AEs, AEs causing discontinuation of study drug(s), deaths and severity.

Outcome measures

Measure	Alemtuzumab 30mg n=86 Participants Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 injection site reaction	49 participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 infection	49 participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 infection related to drug	35 participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 serious AE	46 participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 serious AE related to drug	39 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Discontinued study drug due to AE	21 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Deaths	12 participants
Participants With Treatment-Emergent Adverse Events (TEAE) TEAE with worst severity grade 4	45 participants
Participants With Treatment-Emergent Adverse Events (TEAE) TEAE with worst severity grade 5	8 participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 TEAE	82 participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 TEAE related to drug	80 participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 injection site reaction related to drug	48 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Discontinued study drug due to related AE	20 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Deaths within 30 days of last dose	3 participants
Participants With Treatment-Emergent Adverse Events (TEAE) TEAE with worst severity grade 1	3 participants
Participants With Treatment-Emergent Adverse Events (TEAE) TEAE with worst severity grade 2	8 participants
Participants With Treatment-Emergent Adverse Events (TEAE) TEAE with worst severity grade 3	18 participants

Adverse Events

Alemtuzumab 30mg

Serious events: 46 serious events

Other events: 81 other events

Deaths: 0 deaths

Serious adverse events

Measure	Alemtuzumab 30mg n=86 participants at risk Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Blood and lymphatic system disorders Bone marrow failure	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Febrile neutropenia	7.0% 6/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Idiopathic thrombocytopenic purpura	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Neutropenia	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Pancytopenia	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Thrombocytopenia	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Cardiac disorders Angina unstable	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Cardiac disorders Atrial fibrillation	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Cardiac disorders Left ventricular failure	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Large intestine perforation	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Peritonitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Rectal haemorrhage	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Asthenia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Chills	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Device dislocation	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Localised oedema	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Oedema peripheral	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Pyrexia	7.0% 6/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Hepatobiliary disorders Bile duct obstruction	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Hepatobiliary disorders Cholangitis acute	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Hepatobiliary disorders Hepatorenal syndrome	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Immune system disorders Hypersensitivity	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Abscess neck	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Aspergillosis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Bacteraemia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Bronchitis	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Bronchopneumonia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Bronchopulmonary aspergillosis	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Cellulitis	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Cytomegalovirus infection	10.5% 9/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Ear infection	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Escherichia bacteraemia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Herpes zoster	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Infection	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Lower respiratory tract infection	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Meningitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Parainfluenzae virus infection	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Pneumonia	5.8% 5/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Pneumonia fungal	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Septic shock	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Upper respiratory tract infection	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Urinary tract infection	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Injury, poisoning and procedural complications Fractured ischium	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Cytomegalovirus test positive	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Liver function test abnormal	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Decreased appetite	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Diabetes mellitus	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Hypercalcaemia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Muscular weakness	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Polymyositis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ear neoplasm	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Richter's syndrome	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Cerebrovascular accident	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Encephalitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Headache	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Hypoglycaemic coma	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Sciatica	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Renal and urinary disorders Nephrolithiasis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Renal and urinary disorders Renal failure acute	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Reproductive system and breast disorders Oedema genital	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Pleurisy	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Leukocytoclastic vasculitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Vascular disorders Orthostatic hypotension	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Vascular disorders Shock haemorrhagic	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Vascular disorders Venous thrombosis limb	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.

Other adverse events

Measure	Alemtuzumab 30mg n=86 participants at risk Participants received a target dose of alemtuzumab 30mg by subcutaneous injection three times a week for up to 18 weeks. Some participants started in the Escalation subpopulation and started at a lower dose and escalated from 3mg to 10 mg to the target 30 mg dose in the first 1-2 weeks.
Blood and lymphatic system disorders Anaemia	32.6% 28/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Anaemia haemolytic autoimmune	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Febrile neutropenia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Haemolysis	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Idiopathic thrombocytopenic purpura	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Leukocytosis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Leukopenia	31.4% 27/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Lymphopenia	16.3% 14/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Neutropenia	50.0% 43/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Blood and lymphatic system disorders Thrombocytopenia	19.8% 17/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Cardiac disorders Angina pectoris	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Cardiac disorders Angina unstable	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Cardiac disorders Atrial flutter	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Cardiac disorders Bradycardia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Cardiac disorders Palpitations	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Cardiac disorders Sinus tachycardia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Cardiac disorders Tachycardia	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Ear and labyrinth disorders Ear pain	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Ear and labyrinth disorders Vertigo	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Endocrine disorders Hypothyroidism	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Eye disorders Conjunctivitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Eye disorders Dry eye	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Eye disorders Erythema of eyelid	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Eye disorders Eye haemorrhage	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Eye disorders Eye irritation	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Eye disorders Eye pain	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Eye disorders Lacrimation increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Abdominal distension	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Abdominal pain	8.1% 7/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Abdominal pain upper	5.8% 5/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Aphthous stomatitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Ascites	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Constipation	5.8% 5/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Diarrhoea	17.4% 15/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Dry mouth	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Dyspepsia	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Epigastric discomfort	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Flatulence	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Gastritis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Gastrointestinal disorder	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Gastrooesophageal reflux disease	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Gingival pain	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Haematochezia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Hiatus hernia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Ileus	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Inguinal hernia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Melaena	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Mouth haemorrhage	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Mouth ulceration	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Nausea	19.8% 17/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Odynophagia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Peptic ulcer	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Retching	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Stomatitis	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Tongue coated	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Toothache	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Gastrointestinal disorders Vomiting	16.3% 14/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Asthenia	7.0% 6/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Axillary pain	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Catheter site haematoma	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Chills	23.3% 20/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Fatigue	29.1% 25/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Hypothermia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Influenza like illness	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Injection site erythema	33.7% 29/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Injection site haematoma	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Injection site pain	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Injection site pruritus	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Injection site rash	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Injection site reaction	16.3% 14/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Injection site swelling	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Malaise	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Oedema peripheral	9.3% 8/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Pain	7.0% 6/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
General disorders Pyrexia	34.9% 30/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Hepatobiliary disorders Hepatic function abnormal	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Hepatobiliary disorders Hyperbilirubinaemia	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Immune system disorders Drug hypersensitivity	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Immune system disorders Hypersensitivity	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Immune system disorders Seasonal allergy	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Acute sinusitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Balanitis candida	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Bronchitis	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Cellulitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Clostridial infection	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Cytomegalovirus infection	7.0% 6/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Escherichia urinary tract infection	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Eye infection	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Folliculitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Influenza	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Lower respiratory tract infection	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Nasopharyngitis	8.1% 7/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Oesophageal candidiasis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Oral candidiasis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Oral fungal infection	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Oral herpes	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Oropharyngeal candidiasis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Pneumonia	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Respiratory tract infection	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Rhinitis	7.0% 6/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Sinusitis	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Sinusitis aspergillus	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Systemic candida	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Tinea capitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Tinea infection	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Tracheitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Upper respiratory tract infection	5.8% 5/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Infections and infestations Urinary tract infection	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Injury, poisoning and procedural complications Arthropod bite	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Injury, poisoning and procedural complications Contusion	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Injury, poisoning and procedural complications Fall	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Injury, poisoning and procedural complications Fibula fracture	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Injury, poisoning and procedural complications Post procedural complication	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Injury, poisoning and procedural complications Procedural pain	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Injury, poisoning and procedural complications Thermal burn	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Alanine aminotransferase increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Aspartate aminotransferase increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Beta 2 microglobulin increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Blood alkaline phosphatase increased	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Blood bilirubin increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Blood creatinine increased	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Blood iron decreased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Blood potassium decreased	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Blood pressure increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Blood urea increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Body temperature increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations CD4 lymphocytes decreased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Cytomegalovirus test positive	15.1% 13/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Eosinophil count increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Gamma-glutamyltransferase increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations International normalised ratio increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Neutrophil count decreased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Protein total decreased	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Serum ferritin increased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations Weight decreased	9.3% 8/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Investigations White blood cell count decreased	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Decreased appetite	14.0% 12/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Fluid retention	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Hyperglycaemia	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Hyperkalaemia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Hyperuricaemia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Hypoalbuminaemia	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Hypocalcaemia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Hypokalaemia	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Hyponatraemia	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Increased appetite	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Malnutrition	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Metabolism and nutrition disorders Pseudohyperkalaemia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Arthralgia	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Back pain	5.8% 5/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Bone pain	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Joint effusion	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Joint swelling	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Muscle spasms	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Muscular weakness	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Myalgia	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Pain in extremity	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Polymyositis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Musculoskeletal and connective tissue disorders Spondylitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroma	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Ageusia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Dizziness	8.1% 7/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Dysarthria	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Dyskinesia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Headache	18.6% 16/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Hemiparesis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Hypoaesthesia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Lethargy	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Migraine	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Neuralgia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Paraesthesia	5.8% 5/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Peripheral sensory neuropathy	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Sciatica	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Somnolence	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Syncope	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Nervous system disorders Tremor	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Psychiatric disorders Agitation	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Psychiatric disorders Anxiety	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Psychiatric disorders Confusional state	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Psychiatric disorders Depression	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Psychiatric disorders Insomnia	10.5% 9/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Psychiatric disorders Mood altered	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Psychiatric disorders Neurosis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Psychiatric disorders Stress	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Renal and urinary disorders Dysuria	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Renal and urinary disorders Haematuria	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Renal and urinary disorders Nocturia	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Renal and urinary disorders Pollakiuria	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Renal and urinary disorders Renal failure	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Reproductive system and breast disorders Balanitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Reproductive system and breast disorders Breast oedema	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Cough	16.3% 14/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Dysphonia	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.3% 14/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Orthopnoea	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Pleurisy	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Productive cough	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Sinusitis noninfective	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Tachypnoea	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Throat tightness	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Tonsillar disorder	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Respiratory, thoracic and mediastinal disorders Vasomotor rhinitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Blister	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Dermatitis allergic	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Dry skin	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Ecchymosis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Eczema	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Erythema	10.5% 9/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Hyperhidrosis	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Night sweats	14.0% 12/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Petechiae	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Pityriasis rosea	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Pruritus	12.8% 11/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Pruritus generalised	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Rash	9.3% 8/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Rash generalised	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Rash maculo-papular	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Skin reaction	2.3% 2/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Skin and subcutaneous tissue disorders Urticaria	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Vascular disorders Haematoma	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Vascular disorders Hypertension	4.7% 4/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Vascular disorders Hypotension	7.0% 6/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Vascular disorders Orthostatic hypotension	3.5% 3/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.
Vascular disorders Phlebitis	1.2% 1/86 • Treatment-emergent AEs: up to 18 weeks of treatment plus 45 additional days In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Events are listed independent of relationship to treatment reported.

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Genzyme Medical Information

Genzyme Corporation

Phone: 1-800-745-4447

Results disclosure agreements

• Principal investigator is a sponsor employee In multi-site studies, PI can publish after an independent multi-investigator publication (in which the PI can participate) or 18 months after study completion. PI gives Genzyme a draft 60 days before publication. Genzyme can ask that confidential information be removed, and can defer publication another 60 days upon notifying PI that it will file a patent application on inventions contained in the draft.
• Publication restrictions are in place

Restriction type: OTHER