Trial Outcomes & Findings for A Study to Determine the Activity of Robatumumab (SCH 717454, MK-7454) in Participants With Relapsed or Recurrent Colorectal Cancer (P04721, MK-7454-003) (NCT NCT00551213)

Last Updated: 2018-08-24

Results Overview

FDG-PET was used in this study to detect the biological activity of modulation of the target within the tumor. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 was used to select the target lesion. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs were identified as target lesions and recorded and measured at Baseline. The changes in SUVmax were calculated using the formula: (endpoint SUVmax - baseline SUVmax)/baseline SUVmax as a percentage. If multiple lesions had been measured at a visit, percentages calculated for all target lesions were averaged to find the decrease during the treatment period per participant. FDG SUVmax responder was defined as participants with \>20% decrease in SUVmax after the first cycle of robatumumab in Period 2.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

After the first robatumumab dose in Period 2 (Up to approximately 4 weeks after first robatumumab dose in Period 1)

Results posted on

2018-08-24

Participant Flow

Participant milestones

Participant milestones
Measure	Robatumumab→Robatumumab Participants receive 1 dose of robatumumab 0.3 mg/kg intravenously (IV) followed by 1 dose of robatumumab 10 mg/kg IV once every 2 weeks (Q2W) until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Chemotherapy→Robatumumab Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
Overall Study STARTED	50	17
Overall Study Treated	49	15
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	50	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Robatumumab→Robatumumab Participants receive 1 dose of robatumumab 0.3 mg/kg intravenously (IV) followed by 1 dose of robatumumab 10 mg/kg IV once every 2 weeks (Q2W) until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Chemotherapy→Robatumumab Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
Overall Study Adverse Event	6	3
Overall Study Progressive Disease	41	12
Overall Study Withdrawal by Subject	2	0
Overall Study Not Treated	1	2

Baseline Characteristics

A Study to Determine the Activity of Robatumumab (SCH 717454, MK-7454) in Participants With Relapsed or Recurrent Colorectal Cancer (P04721, MK-7454-003)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Robatumumab→Robatumumab n=50 Participants Participants receive 1 dose of robatumumab 0.3 mg/kg IV followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Chemotherapy→Robatumumab n=17 Participants Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Total n=67 Participants Total of all reporting groups
Age, Continuous	64.7 Years STANDARD_DEVIATION 10.8 • n=99 Participants	61.9 Years STANDARD_DEVIATION 10.6 • n=107 Participants	64.0 Years STANDARD_DEVIATION 10.7 • n=206 Participants
Sex: Female, Male Female	30 Participants n=99 Participants	9 Participants n=107 Participants	39 Participants n=206 Participants
Sex: Female, Male Male	20 Participants n=99 Participants	8 Participants n=107 Participants	28 Participants n=206 Participants

PRIMARY outcome

Timeframe: After the first robatumumab dose in Period 2 (Up to approximately 4 weeks after first robatumumab dose in Period 1)

Population: All participants who received ≥1 dose of robatumumab in Periods 1 and 2 and had SUV data before and after the first dose of robatumumab in Period 2 were included in the analysis. No participants in the Chemotherapy→Robatumumab group received robatumumab in Period 1.

Outcome measures

Outcome measures
Measure	Robatumumab→Robatumumab n=41 Participants Participants receive 1 dose of robatumumab 0.3 mg/kg IV followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Chemotherapy→Robatumumab Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
Number of Participants With a >20% Decrease in Positron Emission Tomography (PET)-Assessed Tumor Glucose Metabolism: Fluorodeoxyglucose (FDG) Standardized Uptake Value (SUV) in the Target Lesion	7 Participants Interval 7.0 to 32.0	—

SECONDARY outcome

Timeframe: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)

Population: All participants who received ≥1 dose of study drug were included in the analysis.

An AE is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the study drug. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.

Outcome measures

Outcome measures
Measure	Robatumumab→Robatumumab n=49 Participants Participants receive 1 dose of robatumumab 0.3 mg/kg IV followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Chemotherapy→Robatumumab n=15 Participants Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
Number of Participants Who Experienced One or More Adverse Events (AEs)	49 Participants	15 Participants

SECONDARY outcome

Timeframe: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)

Population: All participants who received ≥1 dose of robatumumab were included in the analysis.

Tumor response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) scans using RECIST v 1.0 criteria at Screening, at every 8 weeks of robatumumab treatment during Period 2 and at post study. A sum of the longest diameter (LD) for all target lesions was calculated and reported as the baseline sum LD. Overall tumor responses were defined as: Complete Response (CR) - Disappearance of all target lesions; Partial Response (PR) - At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or Stable Disease (SD) - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Outcome measures

Outcome measures
Measure	Robatumumab→Robatumumab n=49 Participants Participants receive 1 dose of robatumumab 0.3 mg/kg IV followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Chemotherapy→Robatumumab n=15 Participants Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
Best Overall Tumor Response Per Investigator Review Partial Response	1 Participants	0 Participants
Best Overall Tumor Response Per Investigator Review Stable Disease	10 Participants	7 Participants
Best Overall Tumor Response Per Investigator Review Progressive Disease	33 Participants	6 Participants
Best Overall Tumor Response Per Investigator Review No post-Baseline assessment	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to last dose of study drug (Up to approximately 18 weeks)

Population: All participants who received ≥1 dose of study drug were included in the analysis.

Outcome measures

Outcome measures
Measure	Robatumumab→Robatumumab n=49 Participants Participants receive 1 dose of robatumumab 0.3 mg/kg IV followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Chemotherapy→Robatumumab n=15 Participants Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
Number of Participants Who Discontinued Study Drug Due to an AE	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)

Population: All participants who received ≥1 dose of robatumumab were included in the analysis.

Tumor response was assessed by CT or MRI scan using RECIST v1.0 criteria at Screening, at every 8 weeks of robatumumab treatment during Period 2 and at post study. A sum of the LD for all target lesions was calculated and reported as the baseline sum LD. Overall tumor responses were defined as: Complete Response (CR) - Disappearance of all target lesions; Partial Response (PR) - At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or Stable Disease (SD) - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Outcome measures

Outcome measures
Measure	Robatumumab→Robatumumab n=49 Participants Participants receive 1 dose of robatumumab 0.3 mg/kg IV followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Chemotherapy→Robatumumab n=15 Participants Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
Best Overall Tumor Response Per Central Review Partial Response	0 Participants	0 Participants
Best Overall Tumor Response Per Central Review Stable Disease	10 Participants	5 Participants
Best Overall Tumor Response Per Central Review Progressive Disease	31 Participants	9 Participants
Best Overall Tumor Response Per Central Review No post-Baseline assessment	8 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and up to approximately 22 weeks

Population: All participants who received ≥1 dose of robatumumab in Periods 1 and 2 were included in the analysis. No participants in the Chemotherapy→Robatumumab group received robatumumab in Period 1.

Tumor growth rate was assessed by CT or MRI scans using RECIST criteria at Screening, at every 8 weeks of robatumumab treatment and at post study. For Pre Baseline 1, tumor growth rate=(sum of longest diameter of target lesions at Baseline - the most recent prior to Baseline)/duration between Baseline and Pre Baseline. For all other cycles, tumor growth rate=(sum of longest diameter of target lesions at a cycle - Baseline)/ duration between Baseline and the cycle. The cycles presented below are relative to the first dose of robatumumab in Period 1.

Outcome measures

Outcome measures
Measure	Robatumumab→Robatumumab n=49 Participants Participants receive 1 dose of robatumumab 0.3 mg/kg IV followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Chemotherapy→Robatumumab Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
Change From Baseline in Tumor Growth Rate Pre Baseline 1 (n=46)	0.49 mm/day Standard Deviation 0.48	—
Change From Baseline in Tumor Growth Rate Cycle 1 (n=24)	0.07 mm/day Standard Deviation 0.67	—
Change From Baseline in Tumor Growth Rate Cycle 2 (n=25)	0.41 mm/day Standard Deviation 0.57	—
Change From Baseline in Tumor Growth Rate Cycle 5 (n=25)	0.53 mm/day Standard Deviation 0.63	—
Change From Baseline in Tumor Growth Rate Cycle 9 (n=7)	0.19 mm/day Standard Deviation 0.26	—

Adverse Events

Chemotherapy→Robatumumab

Serious events: 6 serious events

Other events: 15 other events

Deaths: 0 deaths

Robatumumab→Robatumumab

Serious events: 14 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study.
Publication restrictions are in place

Restriction type: OTHER

Measure	Chemotherapy→Robatumumab n=15 participants at risk Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.	Robatumumab→Robatumumab n=49 participants at risk Participants receive 1 dose of robatumumab 0.3 mg/kg IV followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
Cardiac disorders ATRIAL FIBRILLATION	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders ABDOMINAL DISTENSION	6.7% 1/15 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	0.00% 0/49 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	6.1% 3/49 • Number of events 4 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders CONSTIPATION	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders DIARRHOEA	6.7% 1/15 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 2 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders INTESTINAL OBSTRUCTION	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders NAUSEA	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	6.1% 3/49 • Number of events 4 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders SMALL INTESTINAL OBSTRUCTION	6.7% 1/15 • Number of events 2 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	0.00% 0/49 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders UPPER GASTROINTESTINAL HAEMORRHAGE	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Gastrointestinal disorders VOMITING	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	6.1% 3/49 • Number of events 4 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
General disorders ASTHENIA	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
General disorders CATHETER RELATED COMPLICATION	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
General disorders CHEST PAIN	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
General disorders MALAISE	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 2 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
General disorders PAIN	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 2 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Hepatobiliary disorders CHOLECYSTITIS ACUTE	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Hepatobiliary disorders CHOLELITHIASIS	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Hepatobiliary disorders HEPATIC FUNCTION ABNORMAL	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Infections and infestations BACTERAEMIA	6.7% 1/15 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	0.00% 0/49 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Infections and infestations CELLULITIS	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Infections and infestations KLEBSIELLA BACTERAEMIA	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Infections and infestations PERIHEPATIC ABSCESS	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Infections and infestations PNEUMONIA	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Infections and infestations SEPSIS	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Infections and infestations TOOTH INFECTION	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Metabolism and nutrition disorders DEHYDRATION	13.3% 2/15 • Number of events 2 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Musculoskeletal and connective tissue disorders BACK PAIN	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	6.7% 1/15 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	0.00% 0/49 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Nervous system disorders DIZZINESS	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Psychiatric disorders MENTAL STATUS CHANGES	6.7% 1/15 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	0.00% 0/49 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Renal and urinary disorders RENAL FAILURE ACUTE	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	6.7% 1/15 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Respiratory, thoracic and mediastinal disorders HYPOXIA	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Vascular disorders DEEP VEIN THROMBOSIS	0.00% 0/15 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	2.0% 1/49 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
General disorders CHILLS	6.7% 1/15 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	0.00% 0/49 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
General disorders PYREXIA	6.7% 1/15 • Number of events 2 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	0.00% 0/49 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Hepatobiliary disorders HYPERBILIRUBINAEMIA	6.7% 1/15 • Number of events 2 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	0.00% 0/49 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Respiratory, thoracic and mediastinal disorders ACUTE RESPIRATORY FAILURE	6.7% 1/15 • Number of events 1 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.	0.00% 0/49 • Up to approximately 22 weeks All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.