Trial Outcomes & Findings for Prophylactic Use of Maribavir for the Prevention of Cytomegalovirus (CMV) Disease in Stem Cell Transplant Recipients (NCT NCT00411645)

Last Updated: 2021-06-11

Results Overview

All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

681 participants

Primary outcome timeframe

6 months post-transplant

Results posted on

2021-06-11

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Overall Study STARTED	227	454
Overall Study COMPLETED	146	290
Overall Study NOT COMPLETED	81	164

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Overall Study Consent Withdrawn	13	22
Overall Study Death	56	135
Overall Study Investigator/Sponsor Decision	10	7
Overall Study Lost to Follow-up	2	0

Baseline Characteristics

Prophylactic Use of Maribavir for the Prevention of Cytomegalovirus (CMV) Disease in Stem Cell Transplant Recipients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=227 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=454 Participants Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.	Total n=681 Participants Total of all reporting groups
Age, Continuous	49 years STANDARD_DEVIATION 13.1 • n=5 Participants	49 years STANDARD_DEVIATION 12.5 • n=7 Participants	49 years STANDARD_DEVIATION 12.7 • n=5 Participants
Age, Customized 18 to 44 years	74 Participants n=5 Participants	136 Participants n=7 Participants	210 Participants n=5 Participants
Age, Customized 45 to 64 years	134 Participants n=5 Participants	286 Participants n=7 Participants	420 Participants n=5 Participants
Age, Customized 65 to 75 years	18 Participants n=5 Participants	32 Participants n=7 Participants	50 Participants n=5 Participants
Age, Customized > 75 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	98 Participants n=5 Participants	189 Participants n=7 Participants	287 Participants n=5 Participants
Sex: Female, Male Male	129 Participants n=5 Participants	265 Participants n=7 Participants	394 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months post-transplant

Population: The Intent-to-Treat (ITT) population, defined as all participants who were randomized to one of the therapy groups, regardless of whether the participant received study drug or had any post-baseline evaluations.

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=454 Participants Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation	11 participants	20 participants

SECONDARY outcome

Timeframe: 6 months post-transplant

Population: The ITT population, defined as all participants who were randomized to one of the therapy groups, regardless of whether the participant received study drug or had any post-baseline evaluations.

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=454 Participants Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant pp65 antigenemia or CMV DNA PCR assay	101 participants	183 participants
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant pp65 antigenemia assay	88 participants	143 participants
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant CMV DNA PCR assay	77 participants	152 participants
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-transplant Initiation of anti-CMV therapy	92 participants	172 participants

SECONDARY outcome

Timeframe: 6 months post-transplant

All investigator-determined cases of CMV disease (i.e., CMV infection or CMV organ disease) were adjudicated by an independent, blinded EC. CMV infection was assessed by (1) pp65 antigenemia assay or (2) CMV DNA polymerase chain reaction (PCR). CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=454 Participants Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post- Transplantation	21 days Interval 5.0 to 22.0	22 days Interval 6.0 to 29.0

SECONDARY outcome

Timeframe: Through 12 months post-transplant (Day 1 to 100 days, 6 months, and 12 months post-transplant)

CMV infection was assessed by (1) pp65 antigenemia assay; (2) CMV DNA polymerase chain reaction (PCR); (3) either assay (pp65 antigenemia or CMV DNA PCR); or (4) initiation of anti-CMV therapy. CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA PCR assay in plasma) and fever \>/=38 °C on \>/=2 occasions \>/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell \[WBC\] count \<3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was \>4000/mm3) \>/=24 hours apart, atypical lymphocytosis \>/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002.

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=454 Participants Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Number of Participants With Investigator-determined CMV Disease 100 days post-tranplant	6 participants	16 participants
Number of Participants With Investigator-determined CMV Disease 6 months post-transplant	11 participants	26 participants
Number of Participants With Investigator-determined CMV Disease 12 months post-transplant	13 participants	28 participants

SECONDARY outcome

Timeframe: 100 days post-transplant

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=454 Participants Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation Initiation of anti-CMV therapy	85 participants	139 participants
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation pp65 antigenemia assay	79 participants	120 participants
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation CMV DNA PCR assay	69 participants	126 participants
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation pp65 antigenemia assay or CMV DNA PCR assay	92 participants	157 participants
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation EC-confirmed disease	6 participants	11 participants

SECONDARY outcome

Timeframe: 12 months post-transplant

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=454 Participants Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Number of Participants With EC-confirmed CMV Disease Within 12 Months Post-Transplantation	13 participants	22 participants

SECONDARY outcome

Timeframe: Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)

Population: The ITT Safety (ITT-S) population, defined as participants in the ITT population who received at least one dose of study drug.

Analysis of acute GVHD was based on reported adverse events that mapped to the relevant MedDRA dictionary terms for acute GVHD. The percentage reported is for the occurrence of any grade of acute GVHD.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=451 Participants Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Percent of Participants With Acute Graft-Versus-Host Disease (GVHD) 100 days post-transplant	39 percentage of participants	40 percentage of participants
Percent of Participants With Acute Graft-Versus-Host Disease (GVHD) 6 months post-transplant	43 percentage of participants	44 percentage of participants

SECONDARY outcome

Timeframe: Through 6 months post-transplant (Days 1 to 100 and 6 months post-transplant)

Population: The ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.

Analysis of chronic GVHD was based on reported adverse events that mapped to the relevant MedDRA dictionary terms for chronic GVHD. The percentage reported is for the occurrence of any grade of chronic GVHD.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=451 Participants Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Percent of Participants With Chronic Graft-Versus-Host Disease (GVHD) 100 days post-transplant	5 percentage of participants	6 percentage of participants
Percent of Participants With Chronic Graft-Versus-Host Disease (GVHD) 6 months post-transplant	25 percentage of participants	19 percentage of participants

SECONDARY outcome

Timeframe: Through 12 months post-transplant (Days 1 to 100, 6 months, and 12 months post-transplant)

Population: The ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=223 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=451 Participants Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Number of Participants Who Died Within 12 Months Post-Transplantation 100 days post-transplant	19 participants	30 participants
Number of Participants Who Died Within 12 Months Post-Transplantation 6 months post-transplant	37 participants	88 participants
Number of Participants Who Died Within 12 Months Post-Transplantation 12 months post-transplant	59 participants	139 participants

SECONDARY outcome

Timeframe: 12 hours post-dose after 1 and 4 weeks of treatment

Population: The pharmacokinetic (PK) population, defined as those participants in the ITT population from whom plasma samples were drawn, tested for maribavir concentrations, and complete, evaluable PK data were available.

Pharmacokinetic (PK) profile sampling was performed to evaluate plasma concentrations of Maribavir. During the study drug administration period, blood samples for this purpose were collected on Day 7 (Week 1) and at Week 4. Every effort was made to ensure that doses were administered 12 hours apart on the day before and on the day of PK sampling. Permissible assessment windows for PK profile sampling purposes were +/- 3 days and +/- 5 days for the 1- and 4- week samples, respectively. Samples were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. The validated lower limit of quantitation (LLOQ) in plasma was 0.2 μg/mL.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Plasma Concentration of Maribavir During Treatment 4 weeks post-dose, n=48	2.19 μg/mL Standard Deviation 1.99	—
Plasma Concentration of Maribavir During Treatment 1 week post-dose, n=63	2.11 μg/mL Standard Deviation 2.10	—

SECONDARY outcome

Timeframe: 12 hours post-dose after 1 and 4 weeks of treatment

Population: The PK population, defined as those participants in the ITT population from whom plasma samples were drawn, tested for maribavir concentrations, and complete, evaluable PK data were available.

Pharmacokinetic (PK) profile sampling was performed to evaluate plasma concentrations of VP 44469, a metabolite of Maribavir. During the study drug administration period, blood samples for this purpose were collected on Day 7 (Week 1) and at Week 4. Every effort was made to ensure that doses were administered 12 hours apart on the day before and on the day of PK sampling. Permissible assessment windows for PK profile sampling purposes were +/- 3 days and +/- 5 days for the 1- and 4- week samples, respectively. Samples were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. The validated lower limit of quantitation (LLOQ) in plasma was 0.2 μg/mL.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment 1 week post-dose, n=63	0.56 μg/mL Standard Deviation 0.36	—
Plasma Concentration of Maribavir Metabolite VP 44469 During Treatment 4 weeks post-dose, n=48	0.65 μg/mL Standard Deviation 0.47	—

Adverse Events

Placebo

Serious events: 98 serious events

Other events: 192 other events

Deaths: 0 deaths

Maribavir 100 mg BID

Serious events: 197 serious events

Other events: 408 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=223 participants at risk Participants received placebo twice daily (BID) for up to 12 weeks.	Maribavir 100 mg BID n=451 participants at risk Participants received maribavir 100 mg twice daily (BID) for up to 12 weeks.
Blood and lymphatic system disorders Anaemia	7.6% 17/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	13.3% 60/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	8.1% 18/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	7.3% 33/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	7.2% 16/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	7.3% 33/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Gastrointestinal disorders Abdominal Pain	7.6% 17/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	7.5% 34/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Gastrointestinal disorders Constipation	4.5% 10/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	9.1% 41/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	18.4% 41/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	19.1% 86/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Gastrointestinal disorders Dry Mouth	4.9% 11/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	9.1% 41/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Gastrointestinal disorders Dysgeusia	5.8% 13/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	14.6% 66/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	5.8% 13/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	3.5% 16/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Gastrointestinal disorders Nausea	14.8% 33/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	15.1% 68/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Gastrointestinal disorders Oral Candidiasis	4.5% 10/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	7.5% 34/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	12.1% 27/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	10.6% 48/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
General disorders Fatigue	9.9% 22/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	16.2% 73/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
General disorders Oedema Peripheral	12.6% 28/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	12.9% 58/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
General disorders Pyrexia	12.6% 28/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	10.2% 46/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Immune system disorders Acute Graft Versus Host Disease	22.4% 50/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	25.9% 117/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Infections and infestations Bk Virus Infection	5.8% 13/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	7.3% 33/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Infections and infestations Staphylococcal Bacteraemia	6.7% 15/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	3.8% 17/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Investigations Hepatic Enzyme Increased	6.7% 15/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	6.9% 31/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Investigations Weight Decreased	13.0% 29/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	9.1% 41/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Metabolism and nutrition disorders Anorexia	4.9% 11/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	5.8% 26/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	4.5% 10/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	6.7% 30/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back Pain	4.0% 9/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	5.8% 26/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Nervous system disorders Dizziness	4.9% 11/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	5.8% 26/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Nervous system disorders Headache	9.4% 21/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	9.8% 44/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Nervous system disorders Insomnia	7.2% 16/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	6.0% 27/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Nervous system disorders Tremor	7.2% 16/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	7.1% 32/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Renal and urinary disorders Renal Failure	7.2% 16/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	7.3% 33/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Renal and urinary disorders Urinary Tract Infection	4.0% 9/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	6.2% 28/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	4.9% 11/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	7.8% 35/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Infection	4.0% 9/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	5.5% 25/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Erythema	5.8% 13/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	4.7% 21/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	6.3% 14/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	4.4% 20/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	13.5% 30/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	13.1% 59/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.
Vascular disorders Hypertension	5.8% 13/223 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.	9.5% 43/451 Adverse events are reported for the ITT-S population, defined as participants in the ITT population who received at least one dose of study drug.