Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8558 Monotherapy in Anti-Retroviral-Naïve HIV-1 Infected Participants (MK-8558-002) (NCT NCT03859739)

Last Updated: 2021-05-28

Results Overview

Plasma was collected at baseline and at 168 hours post-dose to determine the change from baseline in HIV-1 ribonucleic acid (RNA) concentration. The log10 plasma HIV-RNA was measured and analyzed based on a longitudinal data analysis (LDA) model containing fixed effects for dose level and time.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

21 participants

Primary outcome timeframe

Baseline and 168 hours post-dose

Results posted on

2021-05-28

Participant Flow

Participants with Human Immunodeficiency Virus Type 1 (HIV-1) infection, who were naïve to anti-retroviral therapy (ART) between 18 and 60 years old (inclusive) were enrolled in this study.

Participant milestones

Participant milestones
Measure	MK-8558 400 mg Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Overall Study STARTED	5	6	6	4
Overall Study COMPLETED	5	6	6	4
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Tolerability, Pharmacokinetics, and Anti-Retroviral Activity of MK-8558 Monotherapy in Anti-Retroviral-Naïve HIV-1 Infected Participants (MK-8558-002)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=6 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.	Total n=21 Participants Total of all reporting groups
Age, Continuous	29.2 Years STANDARD_DEVIATION 5.0 • n=5 Participants	39.3 Years STANDARD_DEVIATION 12.6 • n=7 Participants	32.5 Years STANDARD_DEVIATION 9.8 • n=5 Participants	32.3 Years STANDARD_DEVIATION 18.6 • n=4 Participants	33.6 Years STANDARD_DEVIATION 11.7 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	21 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	19 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	19 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and 168 hours post-dose

Population: Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. One participant from the 900 mg treatment group was excluded from analysis due to important protocol deviation.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=5 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Change From Baseline in Plasma HIV-1 Ribonucleic Acid (RNA) Concentration	-0.82 log10 copies/mL Interval -1.42 to -0.21	-1.00 log10 copies/mL Interval -1.61 to -0.39	-1.61 log10 copies/mL Interval -2.16 to -1.06	-1.81 log10 copies/mL Interval -2.48 to -1.13

PRIMARY outcome

Timeframe: Up to 35 days post-dose

Population: All participants who received at least one dose of treatment.

An Adverse Event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=6 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Number of Participants Experiencing ≥1 Adverse Event (AE)	4 Participants	3 Participants	4 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 35 days post-dose

Population: All participants who received at least one dose of treatment

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=6 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Number of Participants Who Discontinued From the Study Due to an AE	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168 hours post-dose

Plasma was collected from pre-dose up to 168 hours post-dose in order to determine the AUC0-168 for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=5 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Area Under the Concentration-Time Curve From 0 to 168 Hours (AUC0-168) for MK-8558 in Plasma	1740 hr*μM Geometric Coefficient of Variation 24.2	2780 hr*μM Geometric Coefficient of Variation 20.7	5740 hr*μM Geometric Coefficient of Variation 36.3	5340 hr*μM Geometric Coefficient of Variation 15.6

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose

Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the AUC0-last for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=5 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Area Under the Concentration-Time Curve From 0 up to the Last Quantifiable Time-Point (AUC0-last) for MK-8558 in Plasma	2650 hr*μM Geometric Coefficient of Variation 32.9	4450 hr*μM Geometric Coefficient of Variation 16.2	9680 hr*μM Geometric Coefficient of Variation 42.6	8580 hr*μM Geometric Coefficient of Variation 9.6

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose

Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the AUC0-inf for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=5 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) for MK-8558 in Plasma	2840 hr*μM Geometric Coefficient of Variation 37.3	4870 hr*μM Geometric Coefficient of Variation 14.7	11100 hr*μM Geometric Coefficient of Variation 48.9	9520 hr*μM Geometric Coefficient of Variation 9.8

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose

Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the Cmax for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=5 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Maximum Observed Concentration (Cmax) for MK-8558 in Plasma	24.3 μM Geometric Coefficient of Variation 21.7	36.7 μM Geometric Coefficient of Variation 28.9	77.2 μM Geometric Coefficient of Variation 28.9	72.6 μM Geometric Coefficient of Variation 14.3

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose

Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the Tmax for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=5 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Time to Maximum Observed Concentration (Tmax) for MK-8558 in Plasma	4.00 Hours Interval 1.5 to 4.0	4.00 Hours Interval 4.0 to 5.0	4.50 Hours Interval 4.0 to 8.02	4.02 Hours Interval 4.0 to 5.0

SECONDARY outcome

Timeframe: 168 hours post-dose

Plasma was collected at 168 hours post-dose in order to determine the C168hr for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=5 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Concentration at 168 Hours Post-Dose (C168hr) for MK-8558 in Plasma	5.59 μM Geometric Coefficient of Variation 44.0	9.55 μM Geometric Coefficient of Variation 17.7	20.5 μM Geometric Coefficient of Variation 43.4	18.8 μM Geometric Coefficient of Variation 8.1

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose

Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the CL/F for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=5 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Apparent Clearance (CL/F) for MK-8558	0.315 L/hr Geometric Coefficient of Variation 37.3	0.412 L/hr Geometric Coefficient of Variation 14.7	0.321 L/hr Geometric Coefficient of Variation 48.9	0.211 L/hr Geometric Coefficient of Variation 9.8

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose

Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the Vz/F for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=5 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Apparent Volume of Distribution (Vz/F) for MK-8558	56.6 Liters Geometric Coefficient of Variation 21.9	84.4 Liters Geometric Coefficient of Variation 27.5	79.9 Liters Geometric Coefficient of Variation 30.8	45.6 Liters Geometric Coefficient of Variation 20.5

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 240, 336, 504 hours post-dose

Plasma was collected from pre-dose up to 504 hours post-dose in order to determine the t1/2 for MK-8558. Data were natural log transformed and analyzed based on a linear model containing a fixed effect for dose level.

Outcome measures

Outcome measures
Measure	MK-8558 400 mg n=5 Participants Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=5 Participants Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 Participants Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 Participants Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Terminal Half Life (t1/2) for MK-8558	125 Hours Geometric Coefficient of Variation 24.9	142 Hours Geometric Coefficient of Variation 20.1	173 Hours Geometric Coefficient of Variation 22.7	150 Hours Geometric Coefficient of Variation 20.6

Adverse Events

MK-8558 400 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

MK-8558 900 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

MK-8558 1600 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

MK-8558 900 mg Low-Fat

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK-8558 400 mg n=5 participants at risk Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=6 participants at risk Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 participants at risk Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 participants at risk Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Infections and infestations Enteritis infectious	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Infections and infestations Pharyngotonsillitis	20.0% 1/5 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.

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 If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK-8558 400 mg n=5 participants at risk Single oral dose of MK-8558 administered at 400 mg following a 10-hour fast.	MK-8558 900 mg n=6 participants at risk Single oral dose of MK-8558 administered at 900 mg following a 10-hour fast.	MK-8558 1600 mg n=6 participants at risk Single oral dose of MK-8558 administered at 1600 mg following a 10-hour fast.	MK-8558 900 mg Low-Fat n=4 participants at risk Single oral dose of MK-8558 administered at 900 mg following a low-fat meal.
Gastrointestinal disorders Aphthous ulcer	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Gastrointestinal disorders Diarrhoea	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	33.3% 2/6 • Number of events 2 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Gastrointestinal disorders Dyspepsia	20.0% 1/5 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Gastrointestinal disorders Gastritis	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
General disorders Fatigue	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
General disorders Pyrexia	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Infections and infestations Epstein-Barr virus infection	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Infections and infestations Nasopharyngitis	20.0% 1/5 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	33.3% 2/6 • Number of events 2 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Infections and infestations Pharyngotonsillitis	20.0% 1/5 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Infections and infestations Tonsillitis	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Musculoskeletal and connective tissue disorders Arthritis reactive	20.0% 1/5 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Musculoskeletal and connective tissue disorders Myalgia	20.0% 1/5 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Nervous system disorders Headache	40.0% 2/5 • Number of events 2 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	33.3% 2/6 • Number of events 2 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Nervous system disorders Paraesthesia	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Psychiatric disorders Middle insomnia	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	20.0% 1/5 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/5 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/6 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	16.7% 1/6 • Number of events 1 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.	0.00% 0/4 • Adverse events: Up to 35 days post-dose; All-cause mortality: Up to 9 weeks after randomization. All participants who received at least one dose of treatment.