Trial Outcomes & Findings for Safety Study of MK-3641 and MK-7243 Co-administered in Adult Participants With Ragweed and Grass Pollen Induced Allergic Rhinitis (P08607, MK-3641-006) (NCT NCT02256553)

Last Updated: 2017-03-03

Results Overview

Events of local swelling included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, or throat tightness. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the World Allergy Organization (WAO) as local side effects of sublingual immunotherapy (SLIT) that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

102 participants

Primary outcome timeframe

During Period I, Period II and Period III (Up to 6 weeks)

Results posted on

2017-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	MK-3641+MK-7243 Participants receive one MK-7243 tablet, sublingually (SL) once a day (QD) in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.
Period I STARTED	102
Period I COMPLETED	96
Period I NOT COMPLETED	6
Period II STARTED	96
Period II COMPLETED	94
Period II NOT COMPLETED	2
Period III STARTED	94
Period III COMPLETED	91
Period III NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-3641+MK-7243 Participants receive one MK-7243 tablet, sublingually (SL) once a day (QD) in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.
Period I Adverse Event	5
Period I Protocol Violation	1
Period II Adverse Event	1
Period II Subject Moved	1
Period III Adverse Event	3

Baseline Characteristics

Safety Study of MK-3641 and MK-7243 Co-administered in Adult Participants With Ragweed and Grass Pollen Induced Allergic Rhinitis (P08607, MK-3641-006)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-3641+MK-7243 n=102 Participants Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.
Age, Continuous	40.0 Years STANDARD_DEVIATION 12.0 • n=5 Participants
Gender Female	53 Participants n=5 Participants
Gender Male	49 Participants n=5 Participants

PRIMARY outcome

Timeframe: During Period I, Period II and Period III (Up to 6 weeks)

Population: All Treated Participants population consisted of all participants who received ≥1 dose of study drug.

Outcome measures

Outcome measures
Measure	MK-3641+MK-7243 n=102 Participants Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.
Percentage of Participants Who Experienced at Least One Event of Local Swelling Period I	13.7 Percentage of Participants Interval 7.7 to 22.0
Percentage of Participants Who Experienced at Least One Event of Local Swelling Period II	21.6 Percentage of Participants Interval 14.0 to 30.8
Percentage of Participants Who Experienced at Least One Event of Local Swelling Period III	14.7 Percentage of Participants Interval 8.5 to 23.1

SECONDARY outcome

Timeframe: During Period I, Period II and Period III (Up to 6 weeks)

Population: All Treated Participants population consisted of all participants who received ≥1 dose of study drug.

Events of local application site reactions included pharyngeal edema, laryngeal edema, mouth edema, oropharyngeal swelling, palatal edema, tongue swelling/edema, throat tightness, lip swelling/edema, ear pruritus, dysphagia, oral discomfort, glossodynia, oral pruritus, hypoaesthesia oral, throat irritation, paraesthesia oral or stomatitis. Events that occurred during in-clinic dosing were to be monitored and recorded by clinic staff. A Side Effect Report Card was used in Periods I-III to collect information on adverse events identified by the WAO as local side effects of SLIT that occurred within the first 60 minutes after study drug intake. During Period I, participants were to complete the report card once a day after MK-7243 was administered. During Period II, participants were to complete the report card twice a day, once after each tablet was administered. During Period III, participants were to complete the report card once a day after both tablets were administered.

Outcome measures

Outcome measures
Measure	MK-3641+MK-7243 n=102 Participants Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.
Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction Period I	70.6 Percentage of Participants Interval 60.7 to 79.2
Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction Period II	68.6 Percentage of Participants Interval 58.7 to 77.5
Percentage of Participants Who Experienced at Least One Event of Local Application Site Reaction Period III	55.9 Percentage of Participants Interval 45.7 to 65.7

SECONDARY outcome

Timeframe: During Period I, Period II and Period III (Up to 6 weeks)

Population: All Treated Participants population consisted of all participants who received ≥1 dose of study drug.

An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study drug, was also an AE.

Outcome measures

Outcome measures
Measure	MK-3641+MK-7243 n=102 Participants Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) Period I	4.9 Percentage of Participants Interval 1.6 to 11.1
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) Period II	1.0 Percentage of Participants Interval 0.0 to 5.3
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) Period III	2.9 Percentage of Participants Interval 0.6 to 8.4

SECONDARY outcome

Timeframe: During Period I, Period II and Period III (Up to 6 weeks)

Population: All Treated Participants population consisted of all participants who received ≥1 dose of study drug.

Outcome measures

Outcome measures
Measure	MK-3641+MK-7243 n=102 Participants Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.
Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment Period I	4.9 Percentage of Participants Interval 1.6 to 11.1
Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment Period II	3.9 Percentage of Participants Interval 1.1 to 9.7
Percentage of Participants Who Experienced at Least One Local Application Site Reaction That Required Symptomatic Treatment Period III	1.0 Percentage of Participants Interval 0.0 to 5.3

Adverse Events

Period I: MK-7243

Serious events: 0 serious events

Other events: 74 other events

Deaths: 0 deaths

Period II: MK-3641+MK-7243

Serious events: 1 serious events

Other events: 68 other events

Deaths: 0 deaths

Period III: MK-3641+MK-7243

Serious events: 0 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Period I: MK-7243 n=102 participants at risk Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.	Period II: MK-3641+MK-7243 n=96 participants at risk Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.	Period III: MK-3641+MK-7243 n=94 participants at risk Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/102 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	1.0% 1/96 • Number of events 1 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/94 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 45 days prior to submission for publication/presentation.
Publication restrictions are in place

Restriction type: OTHER

Measure	Period I: MK-7243 n=102 participants at risk Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.	Period II: MK-3641+MK-7243 n=96 participants at risk Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.	Period III: MK-3641+MK-7243 n=94 participants at risk Participants receive one MK-7243 tablet, SL QD in the evening for 14 days during Period I; one MK-3641 tablet, SL QD in the morning and one MK-7243 tablet, SL QD in the evening for 14 days during Period II; and one MK-3641 tablet, SL QD, and one MK-7243 tablet, SL QD, within 5 minutes of each other for 14 days during Period III.
Ear and labyrinth disorders Ear pruritus	33.3% 34/102 • Number of events 66 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	34.4% 33/96 • Number of events 68 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	21.3% 20/94 • Number of events 38 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Abdominal pain upper	6.9% 7/102 • Number of events 8 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	11.5% 11/96 • Number of events 21 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	6.4% 6/94 • Number of events 10 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Glossodynia	7.8% 8/102 • Number of events 9 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	9.4% 9/96 • Number of events 13 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	7.4% 7/94 • Number of events 13 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Lip swelling	11.8% 12/102 • Number of events 13 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	14.6% 14/96 • Number of events 19 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	10.6% 10/94 • Number of events 13 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Mouth ulceration	6.9% 7/102 • Number of events 7 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	7.3% 7/96 • Number of events 9 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/94 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/102 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	8.3% 8/96 • Number of events 19 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/94 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Oedema mouth	0.00% 0/102 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	6.2% 6/96 • Number of events 11 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	9.6% 9/94 • Number of events 15 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Oral pruritus	50.0% 51/102 • Number of events 95 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	47.9% 46/96 • Number of events 109 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	35.1% 33/94 • Number of events 54 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Palatal oedema	0.00% 0/102 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	7.3% 7/96 • Number of events 8 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/94 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Paraesthesia oral	5.9% 6/102 • Number of events 7 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/96 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/94 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Swollen tongue	0.00% 0/102 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	10.4% 10/96 • Number of events 13 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/94 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Gastrointestinal disorders Tongue ulceration	7.8% 8/102 • Number of events 9 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/96 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/94 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pharyngeal oedema	0.00% 0/102 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	9.4% 9/96 • Number of events 12 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/94 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.9% 7/102 • Number of events 7 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/96 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	0.00% 0/94 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Throat irritation	52.9% 54/102 • Number of events 93 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	46.9% 45/96 • Number of events 99 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.	30.9% 29/94 • Number of events 46 • Up to 8 weeks All Treated Participants population consisted of all participants who received ≥1 dose of study drug.