Trial Outcomes & Findings for A Study Of The Efficacy And Safety Of Anidulafungin Vs. Fluconazole In The Treatment Of Patients With Candidemia And/Or Other Forms Of Invasive Candidiasis (NCT NCT01176058)

Last Updated: 2015-10-28

Results Overview

Global response included clinical and microbiological success or failure. Success - clinical success (defined as the resolution or significant improvement in signs and symptoms of invasive candidiasis) and microbiological success (defined as the eradication of Candida species present at baseline, as determined on follow-up culture, or the presumed eradication, if culture data were not available \[N/A\] for a participant with a successful clinical response). Failure - Any case that did not meet the criteria for success.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

17 participants

Primary outcome timeframe

End of Intravenous Treatment (Up to Day 42)

Results posted on

2015-10-28

Participant Flow

Participant milestones

Participant milestones
Measure	Anidulafungin Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Overall Study STARTED	9	8
Overall Study COMPLETED	5	5
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Anidulafungin Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Overall Study Adverse Event	1	0
Overall Study Insufficient clinical response	2	2
Overall Study Insufficient mycological response	0	1
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

A Study Of The Efficacy And Safety Of Anidulafungin Vs. Fluconazole In The Treatment Of Patients With Candidemia And/Or Other Forms Of Invasive Candidiasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anidulafungin n=9 Participants Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=8 Participants IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Total n=17 Participants Total of all reporting groups
Age, Customized Between 18 and 44 years	1 participants n=99 Participants	4 participants n=107 Participants	5 participants n=206 Participants
Age, Customized Between 45 and 64 years	4 participants n=99 Participants	2 participants n=107 Participants	6 participants n=206 Participants
Age, Customized More than 65 years	4 participants n=99 Participants	2 participants n=107 Participants	6 participants n=206 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants
Sex: Female, Male Male	8 Participants n=99 Participants	5 Participants n=107 Participants	13 Participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Fever	7 participants n=99 Participants	7 participants n=107 Participants	14 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Hypothermia	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Tachycardia	3 participants n=99 Participants	2 participants n=107 Participants	5 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia White blood cell count decreased	2 participants n=99 Participants	0 participants n=107 Participants	2 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia White blood cell count increased	3 participants n=99 Participants	1 participants n=107 Participants	4 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia White blood cell morphology abnormal	0 participants n=99 Participants	1 participants n=107 Participants	1 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Respiratory rate increased	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Partial pressure of carbon dioxide (PCO2) decrease	0 participants n=99 Participants	1 participants n=107 Participants	1 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Mechanical ventilation	1 participants n=99 Participants	1 participants n=107 Participants	2 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Swelling	1 participants n=99 Participants	2 participants n=107 Participants	3 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Feeling hot	4 participants n=99 Participants	4 participants n=107 Participants	8 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Localized erythema	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Purulence	1 participants n=99 Participants	2 participants n=107 Participants	3 participants n=206 Participants
Presence of Signs and Symptoms of Candidemia Other	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants

PRIMARY outcome

Timeframe: End of Intravenous Treatment (Up to Day 42)

Population: Modified Intent-to-Treat (MITT) population: participants had confirmed diagnosis of candidemia or other forms of invasive candidiasis, received at least 1 dose of study medication treatment, had at least 1 post-baseline efficacy evaluation. N=number of participants with evaluable data; participants with missing or indeterminate data set to Failure.

Outcome measures

Outcome measures
Measure	Anidulafungin n=8 Participants Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=7 Participants IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Percentage of Participants With Global Response at End of Intravenous Treatment (EOIT) Success	62.50 percentage of participants Interval 29.0 to 96.0	71.43 percentage of participants Interval 38.0 to 100.0
Percentage of Participants With Global Response at End of Intravenous Treatment (EOIT) Failure	37.50 percentage of participants Interval 4.0 to 71.0	28.57 percentage of participants Interval 0.0 to 62.0

SECONDARY outcome

Timeframe: End of Treatment (Up to Day 42)

Population: MITT population. N=number of participants with evaluable data; participants with missing or indeterminate data set to Failure.

Global response included clinical and microbiological success or failure. Success - clinical success (defined as the resolution or significant improvement in signs and symptoms of invasive candidiasis) and microbiological success (defined as the eradication of Candida species present at baseline, as determined on follow-up culture, or the presumed eradication, if culture data were N/A for a participant with a successful clinical response). Failure - Any case that did not meet the criteria for success.

Outcome measures

Outcome measures
Measure	Anidulafungin n=8 Participants Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=7 Participants IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Percentage of Participants With Global Response at End of Treatment (EOT) Success	62.50 percentage of participants Interval 29.0 to 96.0	42.86 percentage of participants Interval 6.2 to 79.5
Percentage of Participants With Global Response at End of Treatment (EOT) Failure	37.50 percentage of participants Interval 4.0 to 71.0	57.14 percentage of participants Interval 20.5 to 93.8

SECONDARY outcome

Timeframe: End of Intravenous Treatment (Up to Day 42)

Population: MITT population. N=number of participants with evaluable data; participants with missing data set to Failure.

Clinical response included success and failure. Success included Cure (resolution of signs and symptoms of the Candida infection) and Improvement (significant, but incomplete resolution of signs and symptoms of Candida infection). Failure defined as No significant improvement in signs and symptoms or death due to Candida infection or circumstances prevented an evaluation from being made.

Outcome measures

Outcome measures
Measure	Anidulafungin n=8 Participants Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=7 Participants IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Percentage of Participants With Clinical Response at EOIT Success	75.00 percentage of participants Interval 45.0 to 100.0	71.43 percentage of participants Interval 38.0 to 100.0
Percentage of Participants With Clinical Response at EOIT Failure	25.00 percentage of participants Interval 0.0 to 55.0	28.57 percentage of participants Interval 0.0 to 62.0

SECONDARY outcome

Timeframe: End of Treatment (Up to Day 42)

Population: MITT population. N=number of participants with evaluable data; participants with missing data set to Failure.

Outcome measures

Outcome measures
Measure	Anidulafungin n=8 Participants Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=7 Participants IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Percentage of Participants With Clinical Response at EOT Success	75.00 percentage of participants Interval 45.0 to 100.0	57.14 percentage of participants Interval 20.5 to 93.8
Percentage of Participants With Clinical Response at EOT Failure	25.00 percentage of participants Interval 0.0 to 55.0	42.86 percentage of participants Interval 6.2 to 79.5

SECONDARY outcome

Timeframe: Post treatment follow-up visit (Up to Day 52)

Population: MITT population. N=number of participants with evaluable data; participants with missing data set to Failure.

Outcome measures

Outcome measures
Measure	Anidulafungin n=8 Participants Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=7 Participants IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Percentage of Participants With Clinical Response at Follow-Up Failure	25.00 percentage of participants Interval 0.0 to 55.0	42.86 percentage of participants Interval 6.2 to 79.5
Percentage of Participants With Clinical Response at Follow-Up Success	75.00 percentage of participants Interval 45.0 to 100.0	57.14 percentage of participants Interval 20.5 to 93.8

SECONDARY outcome

Timeframe: End of Intravenous Treatment (Up to Day 42)

Population: MITT population. N=number of participants with evaluable data; participants with missing or indeterminate data are set Failure.

Microbiological Success implies Eradication: culture negative for all Candida species present at baseline (documented), or culture data N/A (presumed). Microbiological Failure implies (1) Persistence: baseline Candida species present in repeat cultures (documented), or culture data N/A (presumed); (2) Recurrence: baseline Candida species isolated following eradication (documented), or culture data N/A (presumed); or (3) Indeterminate: culture data N/A (loss to follow-up or death that was not due to candidiasis or candidemia).

Outcome measures

Outcome measures
Measure	Anidulafungin n=8 Participants Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=7 Participants IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Percentage of Participants With Microbiological Response at EOIT Success	75.00 percentage of participants Interval 45.0 to 100.0	85.71 percentage of participants Interval 59.8 to 100.0
Percentage of Participants With Microbiological Response at EOIT Failure	25.00 percentage of participants Interval 0.0 to 55.0	14.29 percentage of participants Interval 0.0 to 40.2

SECONDARY outcome

Timeframe: End of Treatment (Up to Day 42)

Population: MITT population. N=number of participants with evaluable data; participants with missing or indeterminate data are set to Failure.

Outcome measures

Outcome measures
Measure	Anidulafungin n=8 Participants Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=7 Participants IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Percentage of Participants With Microbiological Response at EOT Success	75.00 percentage of participants Interval 45.0 to 100.0	57.14 percentage of participants Interval 20.5 to 93.8
Percentage of Participants With Microbiological Response at EOT Failure	25.00 percentage of participants Interval 0.0 to 55.0	42.86 percentage of participants Interval 6.2 to 79.5

SECONDARY outcome

Timeframe: Post treatment follow-up visit (Up to Day 52)

Population: MITT population. N=number of participants with evaluable data; participants with missing or indeterminate data are set to Failure.

Outcome measures

Outcome measures
Measure	Anidulafungin n=8 Participants Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=7 Participants IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Percentage of Participants With Microbiological Response at Follow-Up Success	62.50 percentage of participants Interval 29.0 to 96.0	57.14 percentage of participants Interval 20.5 to 93.8
Percentage of Participants With Microbiological Response at Follow-Up Failure	37.50 percentage of participants Interval 4.0 to 71.0	42.86 percentage of participants Interval 6.2 to 79.5

SECONDARY outcome

Timeframe: Baseline to Day 52

Population: Safety population: All participants who have received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Anidulafungin n=9 Participants Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=8 Participants IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Number of Participants Who Died	1 participants	0 participants

Adverse Events

Anidulafungin

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Fluconazole

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Anidulafungin n=9 participants at risk Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=8 participants at risk IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Respiratory, thoracic and mediastinal disorders Respiratory failure	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Disease progression	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

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Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Anidulafungin n=9 participants at risk Intravenous (IV) Anidulafungin loading dose of 200 mg on Day 1 and then 100 mg daily from Day 2. Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.	Fluconazole n=8 participants at risk IV fluconazole 400 mg daily dose from Day 1 (dose reduction according to the participant's tolerability). Participants who completed a minimum of 7 days of IV treatment may have continued with IV treatment or may have been switched to oral fluconazole 400 mg daily up to a maximum of Day 42.
Cardiac disorders Supraventricular tachycardia	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	0.00% 0/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	25.0% 2/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Intestinal obsturction	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	0.00% 0/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	25.0% 2/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chest discomfort	0.00% 0/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chills	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	22.2% 2/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic function abnormal	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	0.00% 0/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Aspartate aminotransferase increased	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations C-reactive protein increased	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations White blood cell count increased	22.2% 2/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	25.0% 2/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypokalaemia	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoproteinaemia	22.2% 2/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Insomnia	0.00% 0/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Haematuria	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Proteinuria	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	0.00% 0/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	12.5% 1/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Pruritus	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Urticaria	11.1% 1/9 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/8 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.