Trial Outcomes & Findings for Study of Fruquintinib in Patients With Metastatic Colorectal Cancer (NCT NCT02196688)

NCT ID: NCT02196688

Last Updated: 2020-06-16

Results Overview

PFS refers to the time interval between the randomization date and the initial record of PD or date of death, whichever is earlier. The presence of PD shall be determined in accordance with the result of the evaluation performed by the investigator, using with RECIST v1.1 criteria. The date of final tumor evaluation will be used as the censoring date for subjects who have not presented with disease progression or death by that date. The date of randomization will be used as the censoring date for subjects which have no death and post-baseline tumor evaluation. If a subject has no post-baseline tumor evaluation but recorded as dead, death will be count as PFS event.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

71 participants

Primary outcome timeframe

From randomization until the date of first documented progression or date of death from any cause, whichever came first.

Results posted on

2020-06-16

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Arm treatment arm- subjects will receive Fruquintinib 5mg orally, Once Daily (QD), plus Best Supportive Care (BSC) for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. fruquintinib: fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off	Control Arm control arm- subjects will receive Fruquintinib placebo 5mg orally, Once Daily (QD), plus Best Supportive Care (BSC) for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. placebo: Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off
Overall Study STARTED	47	24
Overall Study COMPLETED	40	23
Overall Study NOT COMPLETED	7	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Fruquintinib in Patients With Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm n=47 Participants treatment arm- subjects will receive Fruquintinib 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. fruquintinib: fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off	Control Arm n=24 Participants control arm- subjects will receive Fruquintinib placebo 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. placebo: Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off	Total n=71 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	41 Participants n=5 Participants	20 Participants n=7 Participants	61 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	17 Participants n=7 Participants	52 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	47 Participants n=5 Participants	24 Participants n=7 Participants	71 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized ETHNICITY · HAN	47 Participants n=5 Participants	24 Participants n=7 Participants	71 Participants n=5 Participants
Race/Ethnicity, Customized ETHNICITY · NOT HAN	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment China	47 participants n=5 Participants	24 participants n=7 Participants	71 participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until the date of first documented progression or date of death from any cause, whichever came first.

Population: The intention-to-treat set will contain all subjects in the Randomized set (RND) set subjects will be classified according to randomized treatment. The intent-to-treat principle is preserved. The Intention to Treat (ITT) will be used for analyses of PFS, OS, ORR and DCR.

Outcome measures

Outcome measures
Measure	Treatment Arm n=47 Participants treatment arm- subjects will receive Fruquintinib 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. fruquintinib: fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off	Control Arm n=24 Participants control arm- subjects will receive Fruquintinib placebo 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. placebo: Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off
Progression Free Survival (PFS)	4.731 months Interval 2.858 to 5.585	0.986 months Interval 0.953 to 1.577

SECONDARY outcome

Timeframe: From randomization up to progressive disease or end of treatment (EOT) due to any cause.

The ORR is defined as the rate of complete response (CR) or partial response (PR) as the best overall response (BOR), based on evaluation of target lesions and non-target lesions with corroborant radiological method and determined by RECIST v1.1, for the ITT set of response evaluable subjects. Subjects who have no post-baseline tumor evaluation shall be regarded as subjects without ORR. Subjects who qualify for evaluation of CR or PR should have at least one available lesion for measurement with RECIST v1.1.

Outcome measures

Outcome measures
Measure	Treatment Arm n=47 Participants treatment arm- subjects will receive Fruquintinib 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. fruquintinib: fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off	Control Arm n=24 Participants control arm- subjects will receive Fruquintinib placebo 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. placebo: Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off
Objective Response Rate (ORR)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From randomization up to progressive disease or EOT due to any cause.

The DCR is defined as the rate of corroborant CR, PR and stable disease (SD) as the BOR, based on evaluation of target lesions and non-target lesions with corroborant radiological method and determined according to RECIST v1.1, for the ITT set of response evaluable subjects.

Outcome measures

Outcome measures
Measure	Treatment Arm n=47 Participants treatment arm- subjects will receive Fruquintinib 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. fruquintinib: fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off	Control Arm n=24 Participants control arm- subjects will receive Fruquintinib placebo 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. placebo: Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off
Disease Control Rate (DCR)	32 Participants	5 Participants

SECONDARY outcome

Timeframe: From randomization until death due to any cause.

The OS refers to the time interval between the randomization date and the date of death (any cause). The final known date of survival will be used as the censoring date for subjects that have not been reported to have died by the time of analysis.

Outcome measures

Outcome measures
Measure	Treatment Arm n=47 Participants treatment arm- subjects will receive Fruquintinib 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. fruquintinib: fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off	Control Arm n=24 Participants control arm- subjects will receive Fruquintinib placebo 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. placebo: Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off
Over Survival (OS)	7.721 months Interval 6.899 to 10.283	5.520 months Interval 3.614 to 11.302

Adverse Events

Treatment Arm

Serious events: 12 serious events

Other events: 47 other events

Deaths: 38 deaths

Control Arm

Serious events: 5 serious events

Other events: 20 other events

Deaths: 19 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Songhua Fan

Hutchison Medipharma Ltd

Phone: +86 21 2067 3058

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Treatment Arm n=47 participants at risk treatment arm- subjects will receive Fruquintinib 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. fruquintinib: fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off	Control Arm n=24 participants at risk control arm- subjects will receive Fruquintinib placebo 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. placebo: Placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off
Vascular disorders Hypertension	6.4% 3/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Vascular disorders Embolism arterial	2.1% 1/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Vascular disorders Superior vena cava syndrome	2.1% 1/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Gastrointestinal disorders Obstruction intestinal	4.3% 2/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Gastrointestinal disorders Pancreatitis acute	2.1% 1/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	2.1% 1/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Gastrointestinal disorders Functional ileus	0.00% 0/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	4.2% 1/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Hepatobiliary disorders Hepatic function abnormal	2.1% 1/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Hepatobiliary disorders Hepatic damage	2.1% 1/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Hepatobiliary disorders Jaundice cholestatic	2.1% 1/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
General disorders Pyrexia	4.3% 2/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
General disorders Sudden death	0.00% 0/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	4.2% 1/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Investigations Blood bilirubin increased	4.3% 2/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
General disorders Platelet count decreased	0.00% 0/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	4.2% 1/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Nervous system disorders Dyskinesia	2.1% 1/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Nervous system disorders Hepatic coma	0.00% 0/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	4.2% 1/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders Haemoptysis	2.1% 1/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	0.00% 0/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.
Musculoskeletal and connective tissue disorders Muscle weakness	0.00% 0/47 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.	4.2% 1/24 • Adverse event (AE) should be collected from first dose to 30 days after EOT. AEs and laboratory abnormalities that could not be restored or unexplained needed to be collected till recovery or until they could be explained. Serious adverse event (SAE) was collected from informed consent. Only SAEs related to the study drugs should be collected until 30 days after the last dose.