Trial Outcomes & Findings for Safety and Efficacy Study of Posaconazole vs. Fluconazole for Prevention of Invasive Fungal Infection (P05387 AM1)(COMPLETED) (NCT NCT00811928)

NCT ID: NCT00811928

Last Updated: 2017-04-07

Results Overview

Number of participants developing a proven or probable IFI from randomization to the last dosage date (up to 12 weeks \[84 days\]) plus 7 days. IFI diagnosis criteria may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, microbiological criteria with corresponding clinical signs and symptoms.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

252 participants

Primary outcome timeframe

Up to 12 Weeks (84 days) plus 7 days

Results posted on

2017-04-07

Participant Flow

Participant milestones

Participant milestones
Measure	Posaconazole Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Overall Study STARTED	129	123
Overall Study COMPLETED	90	90
Overall Study NOT COMPLETED	39	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Posaconazole Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Overall Study AEs and SAEs Including Death	7	11
Overall Study Withdrawal by Subject	18	12
Overall Study Did Not Take Study Drug	3	0
Overall Study Without Primary Efficacy Endpoint Data	7	4
Overall Study Investigator Decision	2	1
Overall Study Poor Compliance	2	5

Baseline Characteristics

Safety and Efficacy Study of Posaconazole vs. Fluconazole for Prevention of Invasive Fungal Infection (P05387 AM1)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Posaconazole n=117 Participants Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole n=117 Participants Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food	Total n=234 Participants Total of all reporting groups
Age, Continuous	39.3 participants STANDARD_DEVIATION 13.01 • n=5 Participants	40.6 participants STANDARD_DEVIATION 12.50 • n=7 Participants	40.4 participants STANDARD_DEVIATION 12.73 • n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	65 Participants n=7 Participants	127 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	52 Participants n=7 Participants	107 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 12 Weeks (84 days) plus 7 days

Population: The full analysis set (FAS) included all of those randomized participants who received at least one dose of study drug, and had at least one post-treatment follow-up data of primary efficacy variable.

Outcome measures

Outcome measures
Measure	Posaconazole n=117 Participants Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole n=117 Participants Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Number of Participants With Proven or Probable Diagnosis of Invasive Fungal Infection (IFI) During the Treatment Period	4 participants	11 participants

SECONDARY outcome

Timeframe: From randomization date to Day 100

Number of participants who developed a proven or probable IFI from randomization date to Day 100 of follow-up visit. IFI diagnosis criteria may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, microbiological criteria with corresponding clinical signs and symptoms.

Outcome measures

Outcome measures
Measure	Posaconazole n=117 Participants Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole n=117 Participants Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Number of Participants With Proven or Probable Diagnosis of IFI Within 100 Days From Randomization	5 participants	16 participants

SECONDARY outcome

Timeframe: From randomization date to Day 100

The time measured in days to the first occurrence of proven/probable IFI diagnosis in the entire FAS population from randomization to Day 100 of follow-up visit. Participants may not have accepted immediate antifungal treatment and later received antifungal treatment based upon further investigator review of the participant's IFI condition. IFI diagnosis criteria may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, positive blood/biopsy cultures with corresponding clinical signs and symptoms.

Outcome measures

Outcome measures
Measure	Posaconazole n=117 Participants Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole n=117 Participants Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Time From Randomization to the First Onset of Proven or Probable IFI	8 Days	2 Days

SECONDARY outcome

Timeframe: Up to 12 weeks (84 days)

The time measured in days from randomization to the administration of the first concomitant systemic anti-fungal therapy in the entire FAS population. Not all participants who accepted systemic anti-fungal therapy may have had a IFI clinical diagnosis. IFI diagnosis criteria for antifungal therapy administration may include: persistent fever, failure of appropriate broad-spectrum antibiotic treatment concomitant with lower respiratory tract infection symptoms, microbiological criteria with corresponding clinical signs and symptoms.

Outcome measures

Outcome measures
Measure	Posaconazole n=117 Participants Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole n=117 Participants Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Time From Randomization to Administration of First Systemic Antifungal Intravenous (IV) Therapy	4 Days	1 Days

SECONDARY outcome

Timeframe: Up to 12 weeks (84 days)

Clinical failure was defined as follows: * Presence of a proven or probable IFI * Systemic antifungal treatment (IV) for 4 consecutive days or more than 10 days total * Discontinuation due to adverse event (AE) possibly or probably related to study drug * Lost-to-follow-up or discontinuation from the study for any reason with loss to follow-up during the Treatment Phase

Outcome measures

Outcome measures
Measure	Posaconazole n=117 Participants Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole n=117 Participants Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Number of Participants With Clinical Failure During Treatment	37 participants	51 participants

SECONDARY outcome

Timeframe: Randomization date to Day 100

Death from any cause.

Outcome measures

Outcome measures
Measure	Posaconazole n=117 Participants Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole n=117 Participants Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Number of Participants in Whom All-cause Mortality Occurred Within 100 Days From Randomization	3 participants	8 participants

SECONDARY outcome

Timeframe: From randomization date to Day 100

Exact Causes of Death and Their Relationship to IFI Episode Were As Follows: * Unlikely related: participant completed treatment and cause of death was due to primary disease or complication * Possibly related: IFI undergoing treatment without stabilization, or with failure to have a complete remission, where cause of death might have been due to IFI, including progression or relapse of primary disease * Probably related: autopsy or clinical signs suggested that progression of IFI was the probable cause of death

Outcome measures

Outcome measures
Measure	Posaconazole n=117 Participants Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole n=117 Participants Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Number of Participants in Whom Mortality is Unlikely, Possibly, and Probably Related to Fungal Infection Occurred Within 100 Days From Randomization	0 participants	0 participants

Adverse Events

Posaconazole

Serious events: 7 serious events

Other events: 82 other events

Deaths: 0 deaths

Fluconazole

Serious events: 10 serious events

Other events: 81 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Posaconazole n=124 participants at risk Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole n=121 participants at risk Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Blood and lymphatic system disorders Bone marrow depression	0.81% 1/124 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.83% 1/121 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Gastrointestinal disorders Intestinal haemorrhage	0.00% 0/124 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.83% 1/121 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
General disorders Death	0.81% 1/124 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	1.7% 2/121 • Number of events 2 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
General disorders Oedema	0.81% 1/124 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.00% 0/121 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Infections and infestations Sepsis	0.81% 1/124 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.83% 1/121 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Infections and infestations Septic shock	0.00% 0/124 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.83% 1/121 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Nervous system disorders Cerebellar haemorrhage	0.00% 0/124 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.83% 1/121 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Nervous system disorders Cerebral infarction	0.81% 1/124 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.00% 0/121 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Nervous system disorders Consciousness disturbance	0.00% 0/124 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.83% 1/121 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.81% 1/124 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.00% 0/121 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Respiratory, thoracic and mediastinal disorders Respiratory tract infection	0.00% 0/124 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.83% 1/121 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Vascular disorders Cerebral haemorrhage	1.6% 2/124 • Number of events 2 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	0.83% 1/121 • Number of events 1 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Principal Investigator agrees not to publish or publicly present any interim results of the Protocol study without the prior written consent of the SPONSOR. The Principal Investigator further agrees to provide to the SPONSOR thirty (30) days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the Protocol study.
Publication restrictions are in place

Restriction type: OTHER

Measure	Posaconazole n=124 participants at risk Posaconazole oral suspension (40 mg/ml), 200 mg (5mL) three times a day (TID) with meals	Fluconazole n=121 participants at risk Fluconazole 400 mg daily (QD), given as 2 capsules of 50 mg and 2 capsules of 150 mg (a total of 4 capsules) with or without food
Blood and lymphatic system disorders Bone marrow depression	5.6% 7/124 • Number of events 9 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	3.3% 4/121 • Number of events 6 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Gastrointestinal disorders Abdominal discomfort	8.1% 10/124 • Number of events 15 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	4.1% 5/121 • Number of events 5 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Gastrointestinal disorders Anal disorder	8.9% 11/124 • Number of events 12 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	11.6% 14/121 • Number of events 17 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Gastrointestinal disorders Constipation	5.6% 7/124 • Number of events 8 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	3.3% 4/121 • Number of events 4 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Gastrointestinal disorders Diarrhoea	12.1% 15/124 • Number of events 15 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	14.0% 17/121 • Number of events 18 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Gastrointestinal disorders Gingivitis	15.3% 19/124 • Number of events 27 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	14.9% 18/121 • Number of events 19 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Gastrointestinal disorders Mucosal inflammation	10.5% 13/124 • Number of events 13 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	9.9% 12/121 • Number of events 15 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Gastrointestinal disorders Nausea	12.9% 16/124 • Number of events 20 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	12.4% 15/121 • Number of events 16 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Gastrointestinal disorders Vomiting	5.6% 7/124 • Number of events 8 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	5.8% 7/121 • Number of events 7 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
General disorders Chest discomfort	3.2% 4/124 • Number of events 6 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	5.8% 7/121 • Number of events 7 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
General disorders Pain	5.6% 7/124 • Number of events 9 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	5.0% 6/121 • Number of events 6 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
General disorders Pyrexia	31.5% 39/124 • Number of events 61 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	32.2% 39/121 • Number of events 63 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Investigations Hepatic function abnormal	20.2% 25/124 • Number of events 27 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	17.4% 21/121 • Number of events 29 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Metabolism and nutrition disorders Electrolyte imbalance	16.1% 20/124 • Number of events 43 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	12.4% 15/121 • Number of events 29 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Nervous system disorders Dizziness	5.6% 7/124 • Number of events 10 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	1.7% 2/121 • Number of events 2 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Nervous system disorders Headache	7.3% 9/124 • Number of events 10 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	5.0% 6/121 • Number of events 6 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Respiratory, thoracic and mediastinal disorders Cough	9.7% 12/124 • Number of events 22 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	5.0% 6/121 • Number of events 7 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Respiratory, thoracic and mediastinal disorders ENT disorder	18.5% 23/124 • Number of events 31 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	16.5% 20/121 • Number of events 26 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Respiratory, thoracic and mediastinal disorders Respiratory tract infection	13.7% 17/124 • Number of events 21 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	13.2% 16/121 • Number of events 20 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	5.6% 7/124 • Number of events 8 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	3.3% 4/121 • Number of events 4 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.
Skin and subcutaneous tissue disorders Rash	15.3% 19/124 • Number of events 21 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.	15.7% 19/121 • Number of events 23 • From screening to the last dosage date plus 30 days Safety analysis set (SS) included randomized participants who received at least one dose of study drug and had valid data of safety endpoints available for at least one follow-up visit after treatment.