Trial Outcomes & Findings for Amphotericin Alone or in Combination With Fluconazole for AIDS-Associated Meningitis (NCT NCT00145249)

Last Updated: 2012-05-16

Results Overview

Events are reported by MedDRA Preferred Term. Grade 3 - Severe. Incapacitating; inability to perform usual activities and daily tasks; significantly affects clinical status; requires therapeutic intervention. Grade 4 - Life-threatening. AE is life-threatening. Grade 5 - Death. AE causes death.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

143 participants

Primary outcome timeframe

Day 100

Results posted on

2012-05-16

Participant Flow

Subjects were screened and enrolled at 10 sites in the US and 5 sites in Thailand.

Participant milestones

Participant milestones
Measure	AmphoB Standard Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Overall Study STARTED	47	48	48
Overall Study COMPLETED	36	33	31
Overall Study NOT COMPLETED	11	15	17

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Amphotericin Alone or in Combination With Fluconazole for AIDS-Associated Meningitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AmphoB Standard n=45 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=47 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=49 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.	Total n=141 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	45 Participants n=5 Participants	47 Participants n=7 Participants	47 Participants n=5 Participants	139 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Age Continuous	37.1 years STANDARD_DEVIATION 8.47 • n=5 Participants	36.5 years STANDARD_DEVIATION 8.21 • n=7 Participants	35.9 years STANDARD_DEVIATION 9.44 • n=5 Participants	36.5 years STANDARD_DEVIATION 8.69 • n=4 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	15 Participants n=7 Participants	18 Participants n=5 Participants	49 Participants n=4 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	32 Participants n=7 Participants	31 Participants n=5 Participants	92 Participants n=4 Participants
Region of Enrollment United States	14 participants n=5 Participants	14 participants n=7 Participants	14 participants n=5 Participants	42 participants n=4 Participants
Region of Enrollment Thailand	31 participants n=5 Participants	33 participants n=7 Participants	35 participants n=5 Participants	99 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 100

Population: The Regulatory Safety population includes all subjects who were randomized, who receive at least 1 dose of study drug, and who have any on-study data.

Outcome measures

Outcome measures
Measure	AmphoB Standard n=45 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=47 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=49 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Number of Grade 3-5 Adverse Experiences That Are Definitely or Probably Related to Study Drug Hypomagnesaemia	2 Events	1 Events	0 Events
Number of Grade 3-5 Adverse Experiences That Are Definitely or Probably Related to Study Drug Hypokalaemia	0 Events	0 Events	1 Events
Number of Grade 3-5 Adverse Experiences That Are Definitely or Probably Related to Study Drug Anaemia	1 Events	1 Events	0 Events
Number of Grade 3-5 Adverse Experiences That Are Definitely or Probably Related to Study Drug Drug intolerance	1 Events	0 Events	0 Events
Number of Grade 3-5 Adverse Experiences That Are Definitely or Probably Related to Study Drug Creatinine renal clearance increased	0 Events	0 Events	1 Events
Number of Grade 3-5 Adverse Experiences That Are Definitely or Probably Related to Study Drug Psychotic disorder	0 Events	0 Events	1 Events

PRIMARY outcome

Timeframe: Day 100

Population: The Regulatory Safety population includes all subjects who were randomized, who receive at least 1 dose of study drug, and who have any on-study data.

Events are reported by MedDRA Preferred Term. Dose limiting toxicities include events that resulted in study drug being adjusted, interrupted, or discontinued.

Outcome measures

Outcome measures
Measure	AmphoB Standard n=45 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=47 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=49 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Dehydration	0 Events	0 Events	1 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Respiratory failure	0 Events	0 Events	1 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Pneumonia	0 Events	0 Events	1 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens All Events	6 Events	7 Events	14 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Blood creatinine increased	4 Events	1 Events	1 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Creatinine renal clearance decreased	0 Events	1 Events	2 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Creatinine renal clearance increased	0 Events	0 Events	2 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Renal failure	0 Events	2 Events	0 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Renal failure acute	0 Events	1 Events	1 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Azotaemia	0 Events	0 Events	1 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Renal impairment	0 Events	0 Events	1 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Nausea	0 Events	0 Events	1 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Vomiting	0 Events	0 Events	1 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Drug intolerance	1 Events	1 Events	0 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Chills	0 Events	1 Events	0 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Neutropenia	0 Events	0 Events	1 Events
Number of Dose-limiting Toxicities Attributed to Treatment Regimens Hepatitis acute	1 Events	0 Events	0 Events

SECONDARY outcome

Timeframe: 14, 42, and 70 days

Population: The Regulatory Safety Population was used in this analysis, which includes all subjects who were randomized, who received at least 1 dose of study drug, and who have any on-study data.

Number of deaths occurring on study. Day = Day relative to the first dose of study drug.

Outcome measures

Outcome measures
Measure	AmphoB Standard n=45 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=47 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=49 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Number of Deaths Day 43-70	1 Subjects	2 Subjects	5 Subjects
Number of Deaths All Deaths	10 Subjects	8 Subjects	9 Subjects
Number of Deaths Day 1-14	3 Subjects	2 Subjects	1 Subjects
Number of Deaths Day 15-42	3 Subjects	2 Subjects	1 Subjects
Number of Deaths Day >70	3 Subjects	2 Subjects	2 Subjects

SECONDARY outcome

Timeframe: Baseline, 14, 42, and 70 days

Population: The modified Intent to Treat (mITT) population includes all subjects who are randomized to a treatment arm and receive any dose of study drug, who provide any outcome data, and who are determined to have met 2 key criteria for inclusion in the primary analysis - diagnosis of culture-proven cryptococcal meningitis and proven HIV infection.

Number of subjects that have a negative fungal culture at Baseline, Day 14, Day 42, and Day 70.

Outcome measures

Outcome measures
Measure	AmphoB Standard n=46 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=48 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=41 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Number of Subjects With Cerebrospinal Fluid (CSF) Culture Conversion at Multiple Time Points Day 14 - Negative	20 Subjects	13 Subjects	22 Subjects
Number of Subjects With Cerebrospinal Fluid (CSF) Culture Conversion at Multiple Time Points Baseline - Negative	0 Subjects	0 Subjects	0 Subjects
Number of Subjects With Cerebrospinal Fluid (CSF) Culture Conversion at Multiple Time Points Day 42 - Negative	35 Subjects	37 Subjects	36 Subjects
Number of Subjects With Cerebrospinal Fluid (CSF) Culture Conversion at Multiple Time Points Day 70 - Negative	36 Subjects	39 Subjects	38 Subjects

SECONDARY outcome

Timeframe: 14, 42, and 70 days

Population: The mITT population includes all subjects who are randomized to a treatment arm and receive any dose of study drug, who provide any outcome data, and who are determined to have met 2 key criteria for inclusion in the primary analysis - diagnosis of culture-proven cryptococcal meningitis and proven HIV infection.

Treatment success is defined as a composite of the 3 mycologic and clinical measures: CSF culture conversion; neurologically stable or improved; and alive

Outcome measures

Outcome measures
Measure	AmphoB Standard n=46 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=48 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=41 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Number of Subjects Meeting the Key Efficacy Endpoint of Treatment Success Day 14 - Success	19 Subjects	13 Subjects	22 Subjects
Number of Subjects Meeting the Key Efficacy Endpoint of Treatment Success Day 42 - Success	33 Subjects	35 Subjects	33 Subjects
Number of Subjects Meeting the Key Efficacy Endpoint of Treatment Success Day 70 - Success	33 Subjects	36 Subjects	32 Subjects

SECONDARY outcome

Timeframe: 14, 42, and 70 days

Population: The Regulatory Safety population includes all subjects who were randomized, who receive at least 1 dose of study drug, and who have any on-study data

Number of subjects reporting immune reconstitution inflammatory syndrome (IRIS) following treatment. Day = Day relative to first dose of study drug

Outcome measures

Outcome measures
Measure	AmphoB Standard n=45 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=47 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=49 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Number of Subjects Reporting Immune Reconstitution Inflammatory Syndrome (IRIS) Day 1 through 70	2 Subjects	0 Subjects	1 Subjects
Number of Subjects Reporting Immune Reconstitution Inflammatory Syndrome (IRIS) Day 1-14	0 Subjects	0 Subjects	0 Subjects
Number of Subjects Reporting Immune Reconstitution Inflammatory Syndrome (IRIS) Day 15-42	1 Subjects	0 Subjects	0 Subjects
Number of Subjects Reporting Immune Reconstitution Inflammatory Syndrome (IRIS) Day 43-70	1 Subjects	0 Subjects	1 Subjects

SECONDARY outcome

Timeframe: 7, 14, 42, and 70 days

Mean days of hospitalization. Includes days subject was hospitalized prior to study enrollment for current hospital stay.

Outcome measures

Outcome measures
Measure	AmphoB Standard n=46 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=48 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=41 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Mean Days of Hospitalization Day 7	8.9 Days Standard Deviation 1.61	8.8 Days Standard Deviation 2.39	8.1 Days Standard Deviation 2.53
Mean Days of Hospitalization Day 14	15.4 Days Standard Deviation 1.78	15.1 Days Standard Deviation 3.27	13.6 Days Standard Deviation 4.37
Mean Days of Hospitalization Day 42	16.3 Days Standard Deviation 4.22	17.4 Days Standard Deviation 5.91	16.5 Days Standard Deviation 7.03
Mean Days of Hospitalization Day 70	16.7 Days Standard Deviation 4.54	20.1 Days Standard Deviation 11.63	16.6 Days Standard Deviation 8.24

SECONDARY outcome

Timeframe: Days 14 and 70

Population: The study team has since determined that the assay that was to be utilized did not have sufficient sensitivity/specificity for its intended purpose and therefore these results will not be generated.

Isolates were collected at days 14 and 70 for assessment of antifungal susceptibility.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Day 14

Population: The number of subjects tested in the modified Intent to Treat (mITT) population includes all subjects who are randomized to a treatment arm \& receive any dose of study drug, who provide any outcome data, \& who are determined to have met 2 key criteria for inclusion in the primary analysis: diagnosis of cryptococcal meningitis \& HIV infection.

Neurological assessment by Mini-mental Status Exam (MMSE). This is collected as a continuous variable with values from 0-30; where lower scores indicate greater impairment.

Outcome measures

Outcome measures
Measure	AmphoB Standard n=40 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=43 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=40 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Mean Change in Neurological Exam Score From Baseline - Day 14	0.5 Scores on a scale Standard Deviation 4.07	2.1 Scores on a scale Standard Deviation 3.74	3.5 Scores on a scale Standard Deviation 6.25

SECONDARY outcome

Timeframe: Baseline and Day 42

Neurological assessment by Mini-mental Status Exam (MMSE). This is collected as a continuous variable with values from 0-30; where lower scores indicate greater impairment.

Outcome measures

Outcome measures
Measure	AmphoB Standard n=37 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=39 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=37 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Mean Change in Neurological Exam Score From Baseline - Day 42	1.6 Scores on a scale Standard Deviation 2.58	1.8 Scores on a scale Standard Deviation 4.42	3.3 Scores on a scale Standard Deviation 7.9

SECONDARY outcome

Timeframe: Baseline and Day 70

Neurological assessment by Mini-mental Status Exam (MMSE). This is collected as a continuous variable with values from 0-30; where lower scores indicate greater impairment.

Outcome measures

Outcome measures
Measure	AmphoB Standard n=37 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=34 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=30 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Mean Change in Neurological Exam Score From Baseline - Day 70	1.5 Scores on a scale Standard Deviation 3.28	2.2 Scores on a scale Standard Deviation 3.58	4.2 Scores on a scale Standard Deviation 6.84

SECONDARY outcome

Timeframe: Baseline and Day 168

Neurological assessment by Mini-mental Status Exam (MMSE). This is collected as a continuous variable with values from 0-30; where lower scores indicate greater impairment.

Outcome measures

Outcome measures
Measure	AmphoB Standard n=33 Participants Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=27 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=28 Participants Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Mean Change in Neurological Exam Score From Baseline - Day 168	2.0 Scores on a scale Standard Deviation 2.28	2.8 Scores on a scale Standard Deviation 3.92	4.4 Scores on a scale Standard Deviation 7.58

Adverse Events

AmphoB Standard

Serious events: 22 serious events

Other events: 44 other events

Deaths: 0 deaths

AmphoB+Fluc400

Serious events: 17 serious events

Other events: 47 other events

Deaths: 0 deaths

AmphoB + Fluc800

Serious events: 26 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Peter G. Pappas, MD

University of Alabama at Birmingham

Phone: 205-934-9951

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	AmphoB Standard n=45 participants at risk Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=47 participants at risk Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=49 participants at risk Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Infections and infestations Sepsis	8.9% 4/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.4% 3/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Meningitis cryptococcal	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Pneumocystis jiroveci pneumonia	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.3% 2/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Sinusitis	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.1% 2/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations AIDS related complication	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Arthritis bacterial	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations End stage AIDS	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Escherichia sepsis	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Herpes zoster	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Pneumonia	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Pseudomonal bacteraemia	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Sepsis syndrome	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Staphylococcal infection	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Toxoplasmosis	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Intracranial pressure increased	6.7% 3/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.3% 2/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.1% 2/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Convulsion	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.4% 3/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Headache	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Brain compression	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Cerebral haemorrhage	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Cerebral infarction	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Depressed level of consciousness	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Hemiparesis	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Hemiplegia	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Metabolism and nutrition disorders Dehydration	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.1% 3/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Metabolism and nutrition disorders Cachexia	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.1% 2/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Blood and lymphatic system disorders Neutropenia	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.1% 2/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Blood and lymphatic system disorders Anaemia	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Immune system disorders Immune reconstitution syndrome	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Immune system disorders Hypersensitivity	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Hepatobiliary disorders Cholangitis	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Hepatobiliary disorders Hepatitis	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Hepatobiliary disorders Hepatitis acute	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Cardiac disorders Cardiac failure congestive	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Cardiac disorders Congestive cardiomyopathy	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Gastrointestinal disorders Abdominal pain	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.

Other adverse events
Measure	AmphoB Standard n=45 participants at risk Amphotericin B 0.7 mg/kg for 14 day followed by fluconazole 400 mg daily for 8 weeks. For subjects in the standard therapy arm whose Amphotericin B dose is continued beyond 14 days, fluconazole initiation will be delayed.	AmphoB+Fluc400 n=47 participants at risk Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 400 mg/day for the first 14 days, then the randomized dose of fluconazole at 400 mg/day respectively for an additional 8 weeks.	AmphoB + Fluc800 n=49 participants at risk Amphotericin B 0.7 mg/kg and the randomized dose of fluconazole at 800 mg/day for the first 14 days, then the randomized dose of fluconazole at 800 mg/day respectively for an additional 8 weeks.
Metabolism and nutrition disorders Hypokalaemia	84.4% 38/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	80.9% 38/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	79.6% 39/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Metabolism and nutrition disorders Hypomagnesaemia	60.0% 27/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	70.2% 33/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	63.3% 31/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Metabolism and nutrition disorders Anorexia	26.7% 12/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	17.0% 8/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	14.3% 7/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Metabolism and nutrition disorders Hyponatraemia	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	14.9% 7/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	12.2% 6/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Metabolism and nutrition disorders Hyperkalaemia	11.1% 5/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.3% 2/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.1% 3/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Gastrointestinal disorders Vomiting	31.1% 14/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	29.8% 14/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	32.7% 16/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Gastrointestinal disorders Nausea	8.9% 4/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	29.8% 14/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	32.7% 16/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Gastrointestinal disorders Constipation	13.3% 6/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	18.4% 9/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Gastrointestinal disorders Diarrhoea	6.7% 3/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	12.8% 6/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	12.2% 6/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Blood and lymphatic system disorders Anaemia	46.7% 21/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	57.4% 27/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	49.0% 24/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Blood and lymphatic system disorders Thrombocytopenia	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.2% 4/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Sepsis	11.1% 5/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	14.9% 7/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	12.2% 6/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Herpes simplex	8.9% 4/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	10.2% 5/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Sinusitis	15.6% 7/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	12.2% 6/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Bacteraemia	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.4% 3/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	10.2% 5/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Herpes zoster	6.7% 3/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Oral candidiasis	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.3% 2/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.2% 4/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Pneumocystis jiroveci pneumonia	6.7% 3/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.4% 3/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Headache	22.2% 10/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	27.7% 13/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	28.6% 14/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Convulsion	11.1% 5/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	10.6% 5/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.1% 2/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Nervous system disorders Intracranial pressure increased	6.7% 3/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.3% 2/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.1% 2/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Vascular disorders Phlebitis	8.9% 4/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	10.6% 5/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	16.3% 8/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Vascular disorders Thrombophlebitis	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	12.2% 6/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Vascular disorders Hypotension	8.9% 4/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.3% 2/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.1% 2/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Skin and subcutaneous tissue disorders Rash papular	8.9% 4/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.1% 3/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Skin and subcutaneous tissue disorders Rash	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.3% 2/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	10.2% 5/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Psychiatric disorders Insomnia	24.4% 11/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	14.9% 7/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	22.4% 11/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
General disorders Pyrexia	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	12.2% 6/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
General disorders Chills	8.9% 4/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.1% 2/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Investigations Blood creatinine increased	8.9% 4/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.1% 2/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Musculoskeletal and connective tissue disorders Back pain	6.7% 3/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.0% 1/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Metabolism and nutrition disorders Dehydration	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.1% 3/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Gastrointestinal disorders Dyspepsia	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.5% 4/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Gastrointestinal disorders Abdominal Pain	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.4% 3/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Blood and lymphatic system disorders Neutropenia	4.4% 2/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	2.1% 1/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.1% 3/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Infections and infestations Upper respiratory tract infection	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	8.2% 4/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Vascular disorders Hypertension	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.4% 3/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.1% 2/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Skin and subcutaneous tissue disorders Pruritus	2.2% 1/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	4.3% 2/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.1% 3/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.4% 3/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.
Psychiatric disorders Depression	0.00% 0/45 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	0.00% 0/47 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.	6.1% 3/49 • Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 100. If a subject experienced more than 1 of a given AE, the subjects is counted only once for that AE. If a subject experienced more than one AE in a system organ class (SOC), the subject is counted only once in that SOC.