Trial Outcomes & Findings for A Study to Evaluate the Effect of Gefapixant (AF-219/MK-7264) on Methacholine Hyper-reactivity in Participants With Asthma (MK-7264-009) (NCT NCT01993329)

NCT ID: NCT01993329

Last Updated: 2021-02-03

Results Overview

The provocative concentration (PC) of inhaled methacholine required to reduce forced expiratory volume in 1 second (FEV1) by 20% (PC20) was calculated from the methacholine challenge at screening and 2 hours (+15 minutes) post dose on Day 3 of each Treatment Period using a five-breath dosimeter method. The primary endpoint was the methacholine PC20 value normalized by means of a log (base 2) transformation, at 2 dose levels compared with placebo in participants with asthma following provocation with methacholine.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Screening (Day -21 to Day -1) and Day 3

Results posted on

2021-02-03

Participant Flow

A Screening Phase of up to 21 days ensured that each participant met all the specified inclusion and none of the exclusion criteria. Screening procedures were performed over at least 2 days

Participant milestones

Participant milestones
Measure	Gefapixant 50 mg>Gefapixant 300 mg>Placebo Gefapixant 50 mg twice daily (BID) on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2 followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Gefapixant 50 mg>Placebo>Gefapixant 300 mg Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Gefapixant 300 mg>Gefapixant 50 mg>Placebo Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Gefapixant 300 mg>Placebo>Gefapixant 50 mg Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Placebo> Gefapixant 50 mg>Gefapixant 300 mg Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Placebo> Gefapixant 300 mg>Gefapixant 50 mg Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3
Period 1 STARTED	3	4	3	3	3	4
Period 1 COMPLETED	3	4	3	3	3	4
Period 1 NOT COMPLETED	0	0	0	0	0	0
Wash-out STARTED	3	4	3	3	3	3
Wash-out COMPLETED	3	3	3	3	3	3
Wash-out NOT COMPLETED	0	1	0	0	0	0
Period 2 STARTED	3	4	3	3	3	4
Period 2 COMPLETED	3	4	3	3	3	3
Period 2 NOT COMPLETED	0	0	0	0	0	1
Period 3 STARTED	3	3	3	3	3	3
Period 3 COMPLETED	3	3	3	3	3	3
Period 3 NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Gefapixant 50 mg>Gefapixant 300 mg>Placebo Gefapixant 50 mg twice daily (BID) on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2 followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Gefapixant 50 mg>Placebo>Gefapixant 300 mg Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Gefapixant 300 mg>Gefapixant 50 mg>Placebo Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Gefapixant 300 mg>Placebo>Gefapixant 50 mg Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Placebo> Gefapixant 50 mg>Gefapixant 300 mg Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Placebo> Gefapixant 300 mg>Gefapixant 50 mg Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3
Period 2 Adverse Event	0	0	0	0	0	1
Wash-out Personal reasons	0	1	0	0	0	0

Baseline Characteristics

A Study to Evaluate the Effect of Gefapixant (AF-219/MK-7264) on Methacholine Hyper-reactivity in Participants With Asthma (MK-7264-009)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gefapixant 50 mg>Gefapixant 300 mg>Placebo n=3 Participants Gefapixant 50 mg twice daily (BID) on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2 followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Gefapixant 50 mg>Placebo>Gefapixant 300 mg n=4 Participants Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Gefapixant 300 mg>Gefapixant 50 mg>Placebo n=3 Participants Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Gefapixant 300 mg>Placebo>Gefapixant 50 mg n=3 Participants Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Placebo> Gefapixant 50 mg>Gefapixant 300 mg n=3 Participants Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Placebo> Gefapixant 300 mg>Gefapixant 50 mg n=4 Participants Placebo BID on Days 1-3 and once daily in the morning Day 4 in Period 1, followed by a washout period of ≥7 days, then Gefapixant 300 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 2, followed by a washout period of ≥7 days, then Gefapixant 50 mg BID on Days 1-3 and once daily in the morning Day 4 in Period 3	Total n=20 Participants Total of all reporting groups
Age, Continuous	35.7 Years STANDARD_DEVIATION 7.0 • n=5 Participants	27.5 Years STANDARD_DEVIATION 7.6 • n=7 Participants	43.3 Years STANDARD_DEVIATION 7.6 • n=5 Participants	31.3 Years STANDARD_DEVIATION 8.0 • n=4 Participants	52.7 Years STANDARD_DEVIATION 8.1 • n=21 Participants	40.0 Years STANDARD_DEVIATION 14.3 • n=10 Participants	38.0 Years STANDARD_DEVIATION 11.7 • n=115 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	7 Participants n=115 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	2 Participants n=21 Participants	2 Participants n=10 Participants	13 Participants n=115 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	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	0 Participants n=10 Participants	0 Participants n=115 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	4 Participants n=10 Participants	20 Participants n=115 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	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) American Indian or Alaska Native	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	0 Participants n=10 Participants	0 Participants n=115 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	0 Participants n=10 Participants	0 Participants n=115 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	0 Participants n=10 Participants	0 Participants n=115 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	0 Participants n=10 Participants	0 Participants n=115 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	4 Participants n=10 Participants	20 Participants n=115 Participants
Race (NIH/OMB) More than one race	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	0 Participants n=10 Participants	0 Participants n=115 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	0 Participants n=10 Participants	0 Participants n=115 Participants

PRIMARY outcome

Timeframe: Screening (Day -21 to Day -1) and Day 3

Population: Analysis population included all randomized participants who received at least 1 dose of study medication and had any post-dose efficacy evaluations for a given Treatment Period and who completed all 3 Treatment Periods.

Outcome measures

Outcome measures
Measure	Gefapixant 50 n=18 Participants Participants received gefapixant 50 mg twice daily for 3.5 days during one period of the study	Gefapixant 300 n=18 Participants Participants received gefapixant 300 mg twice daily for 3.5 days during one period of the study	Placebo n=18 Participants Participants received placebo twice daily for 3.5 days during each period of the study	Placebo Participants received placebo twice daily for 3.5 days during each period of the study
Provocative Concentration (PC20) After Methacholine Challenge	0.91 log [mg/mL] Geometric Coefficient of Variation 214.4	0.84 log [mg/mL] Geometric Coefficient of Variation 181.0	0.82 log [mg/mL] Geometric Coefficient of Variation 260.1	—

SECONDARY outcome

Timeframe: Screening (Day -21 to Day -1) and Day 3

Serial FEV1 was measured post inhalation of methacholine challenges for 90 minutes. The highest FEV1 at 5, 15, 30, 45, 60, and 90 minutes following methacholine challenge were evaluated for each subject. The minimum highest FEV1 was derived using the first three available measures that cover the first 30 minutes after the challenge.

Outcome measures

Outcome measures
Measure	Gefapixant 50 n=18 Participants Participants received gefapixant 50 mg twice daily for 3.5 days during one period of the study	Gefapixant 300 n=18 Participants Participants received gefapixant 300 mg twice daily for 3.5 days during one period of the study	Placebo n=18 Participants Participants received placebo twice daily for 3.5 days during each period of the study	Placebo n=18 Participants Participants received placebo twice daily for 3.5 days during each period of the study
Highest FEV1 After Methacholine Challenge +15 minutes	2.69 Liters Standard Deviation 0.75	2.72 Liters Standard Deviation 0.80	2.67 Liters Standard Deviation 0.83	2.77 Liters Standard Deviation 0.84
Highest FEV1 After Methacholine Challenge +45 minutes	2.93 Liters Standard Deviation 0.83	3.02 Liters Standard Deviation 0.88	2.99 Liters Standard Deviation 0.90	3.03 Liters Standard Deviation 0.93
Highest FEV1 After Methacholine Challenge +60 minutes	2.99 Liters Standard Deviation 0.84	3.11 Liters Standard Deviation 0.93	3.06 Liters Standard Deviation 0.91	3.14 Liters Standard Deviation 0.96
Highest FEV1 After Methacholine Challenge +90 minutes	3.10 Liters Standard Deviation 0.88	3.15 Liters Standard Deviation 0.93	3.12 Liters Standard Deviation 0.90	3.18 Liters Standard Deviation 0.95
Highest FEV1 After Methacholine Challenge + 5 minutes	2.44 Liters Standard Deviation 0.66	2.53 Liters Standard Deviation 0.70	2.43 Liters Standard Deviation 0.71	2.54 Liters Standard Deviation 0.75
Highest FEV1 After Methacholine Challenge +30 minutes	2.86 Liters Standard Deviation 0.82	2.93 Liters Standard Deviation 0.88	2.83 Liters Standard Deviation 0.86	2.94 Liters Standard Deviation 0.89
Highest FEV1 After Methacholine Challenge Minimum Highest FEV1	2.44 Liters Standard Deviation 0.66	2.53 Liters Standard Deviation 0.70	2.43 Liters Standard Deviation 0.71	2.54 Liters Standard Deviation 0.75

Adverse Events

Gefapixant 50 mg

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Gefapixant 300 mg

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

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 No data collected as part of this study will be utilized in any written work, including publications, without the written consent of Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	Gefapixant 50 mg n=19 participants at risk Participants received gefapixant 50 mg twice daily for 3.5 days during one period of the study	Gefapixant 300 mg n=19 participants at risk Participants received gefapixant 300 mg twice daily for 3.5 days during one period of the study	Placebo n=20 participants at risk Participants received placebo twice daily for 3.5 days during each period of the study
Gastrointestinal disorders Irritable bowel syndrome	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/19 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/19 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	15.8% 3/19 • Number of events 3 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	5.0% 1/20 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
General disorders Thirst	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Soft tissue injury	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/19 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.00% 0/19 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Dysgeusia	68.4% 13/19 • Number of events 13 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	94.7% 18/19 • Number of events 18 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Headache	42.1% 8/19 • Number of events 9 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	31.6% 6/19 • Number of events 6 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	30.0% 6/20 • Number of events 6 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Hypogeusia	10.5% 2/19 • Number of events 2 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	5.0% 1/20 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Psychiatric disorders Anxiety	0.00% 0/19 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Renal and urinary disorders Nocturia	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	10.5% 2/19 • Number of events 2 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/19 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	10.5% 2/19 • Number of events 2 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/19 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/19 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Macule	0.00% 0/19 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	5.3% 1/19 • Number of events 1 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.	0.00% 0/20 • Up to 42 days All cause mortality events were assessed for all randomized participants. Non-serious and Serious AEs were assessed for all participants who were randomized and received at least one dose of study drug.