Trial Outcomes & Findings for Defining Skin Immunity of a Bite of Key Insect Vectors in Humans (NCT NCT03641339)

NCT ID: NCT03641339

Last Updated: 2021-12-08

Results Overview

Number of differentially expressed genes between bitten and unbitten skin with adjusted p-values (adjusted for multiple comparisons) of \< 0.05 and a minimum absolute fold change \> 4 in samples derived from skin biopsies for the three vector groups - Aedes aegypti, Anopheles gambiae, Lutzomyia longipalpis

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 95 participants
• Primary outcome timeframe: Up to 48 hours post bite
• Results posted on: 2021-12-08

Participant Flow

Participant milestones

Measure	Single Exposure Cohort A: Aedes Aegypti One vector feeding: Participants will undergo one feeding by Aedes aegypti mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Aedes Aegypti Four vector feeding: Participants will undergo four feedings by Aedes aegypti mosquitos each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Anopheles Gambiae One vector feeding: Participants will undergo one feeding by Anopheles gambiae mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Anopheles Gambiae Four vector feeding: Participants will undergo four feedings by Anopheles gambiae mosquitoes each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Lutzomyia Longipalpis One vector feeding: Participants will undergo one feeding by Lutzomyia longipalpis and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Lutzomyia Longipalpis Four vector feeding: Participants will undergo four feedings by Lutzomyia longipalpis each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding
Overall Study STARTED	16	17	15	16	15	16
Overall Study COMPLETED	15	15	15	14	15	15
Overall Study NOT COMPLETED	1	2	0	2	0	1

Reasons for withdrawal

Measure	Single Exposure Cohort A: Aedes Aegypti One vector feeding: Participants will undergo one feeding by Aedes aegypti mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Aedes Aegypti Four vector feeding: Participants will undergo four feedings by Aedes aegypti mosquitos each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Anopheles Gambiae One vector feeding: Participants will undergo one feeding by Anopheles gambiae mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Anopheles Gambiae Four vector feeding: Participants will undergo four feedings by Anopheles gambiae mosquitoes each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Lutzomyia Longipalpis One vector feeding: Participants will undergo one feeding by Lutzomyia longipalpis and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Lutzomyia Longipalpis Four vector feeding: Participants will undergo four feedings by Lutzomyia longipalpis each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding
Overall Study Physician Decision	1	0	0	0	0	0
Overall Study Withdrawal by Subject	0	2	0	2	0	1

Baseline Characteristics

Defining Skin Immunity of a Bite of Key Insect Vectors in Humans

Baseline characteristics by cohort

Measure	Single Exposure Cohort A: Aedes Aegypti n=15 Participants One vector feeding: Participants will undergo one feeding by Aedes aegypti mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Aedes Aegypti n=15 Participants Four vector feeding: Participants will undergo four feedings by Aedes aegypti mosquitos each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Anopheles Gambiae n=15 Participants One vector feeding: Participants will undergo one feeding by Anopheles gambiae mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Anopheles Gambiae n=14 Participants Four vector feeding: Participants will undergo four feedings by Anopheles gambiae mosquitoes each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Lutzomyia Longipalpis n=15 Participants One vector feeding: Participants will undergo one feeding by Lutzomyia longipalpis and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Lutzomyia Longipalpis n=15 Participants Four vector feeding: Participants will undergo four feedings by Lutzomyia longipalpis each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Total n=89 Participants Total of all reporting groups
Age, Continuous	31.27 years STANDARD_DEVIATION 8.36 • n=5 Participants	30.67 years STANDARD_DEVIATION 9.40 • n=7 Participants	35.60 years STANDARD_DEVIATION 9.66 • n=5 Participants	33.07 years STANDARD_DEVIATION 9.42 • n=4 Participants	32.47 years STANDARD_DEVIATION 11.62 • n=21 Participants	32.73 years STANDARD_DEVIATION 11.44 • n=8 Participants	32.62 years STANDARD_DEVIATION 9.89 • n=8 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	12 Participants n=7 Participants	9 Participants n=5 Participants	8 Participants n=4 Participants	11 Participants n=21 Participants	11 Participants n=8 Participants	57 Participants n=8 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	4 Participants n=21 Participants	4 Participants n=8 Participants	32 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants	4 Participants n=8 Participants	15 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	12 Participants n=4 Participants	11 Participants n=21 Participants	11 Participants n=8 Participants	72 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	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	0 Participants n=8 Participants	2 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 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=8 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	6 Participants n=8 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=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	4 Participants n=8 Participants	19 Participants n=8 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	8 Participants n=4 Participants	7 Participants n=21 Participants	9 Participants n=8 Participants	49 Participants n=8 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	9 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=8 Participants	5 Participants n=8 Participants
Region of Enrollment United States	15 participants n=5 Participants	15 participants n=7 Participants	15 participants n=5 Participants	14 participants n=4 Participants	15 participants n=21 Participants	15 participants n=8 Participants	89 participants n=8 Participants

PRIMARY outcome

Timeframe: Up to 48 hours post bite

Population: Every participant who had skin biopsies.

Number of differentially expressed genes between bitten and unbitten skin with adjusted p-values (adjusted for multiple comparisons) of < 0.05 and a minimum absolute fold change > 4 in samples derived from skin biopsies for the three vector groups - Aedes aegypti, Anopheles gambiae, Lutzomyia longipalpis

Outcome measures

Measure	Single Exposure Cohort A: Aedes Aegypti n=7 Participants One vector feeding: Participants will undergo one feeding by Aedes aegypti mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Aedes Aegypti n=7 Participants Four vector feeding: Participants will undergo four feedings by Aedes aegypti mosquitos each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Anopheles Gambiae n=7 Participants One vector feeding: Participants will undergo one feeding by Anopheles gambiae mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Anopheles Gambiae n=7 Participants Four vector feeding: Participants will undergo four feedings by Anopheles gambiae mosquitoes each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Lutzomyia Longipalpis n=7 Participants One vector feeding: Participants will undergo one feeding by Lutzomyia longipalpis and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Lutzomyia Longipalpis n=7 Participants Four vector feeding: Participants will undergo four feedings by Lutzomyia longipalpis each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding
Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups 30 minutes post bite	18 number of differentially expressed genes	NA number of differentially expressed genes Participants in Cohort B did not have a 30 minute time point per study protocol	1 number of differentially expressed genes	NA number of differentially expressed genes Participants in Cohort B did not have a 30 minute time point per study protocol	5 number of differentially expressed genes	NA number of differentially expressed genes Participants in Cohort B did not have a 30 minute time point per study protocol
Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups 4 hours post bite	227 number of differentially expressed genes	179 number of differentially expressed genes	12 number of differentially expressed genes	72 number of differentially expressed genes	172 number of differentially expressed genes	204 number of differentially expressed genes
Number of Differentially Expressed Genes Between Bitten (Case) Versus Unbitten (Control) Skin for Each of the Three Vector Groups 48 hours post bite	NA number of differentially expressed genes Participants in Cohort A did not have a 48 hour time point per study protocol.	503 number of differentially expressed genes	NA number of differentially expressed genes Participants in Cohort A did not have a 48 hour time point per study protocol	982 number of differentially expressed genes	NA number of differentially expressed genes Participants in Cohort A did not have a 48 hour time point per study protocol	797 number of differentially expressed genes

PRIMARY outcome

Timeframe: Up to 48 hours post bite

Population: Every participant who had skin biopsies.

Number of participants with certain types of inflammatory cell infiltrates, which includes neutrophils, mononuclear cells, and eosinophils, in the skin biopsies of bitten skin at 30 minutes, 4 hours, and 48 hours post bite for each of the three vector groups - Aedes aegypti, Anopheles gambiae, and Lutzomyia longipalpis

Outcome measures

Measure	Single Exposure Cohort A: Aedes Aegypti n=8 Participants One vector feeding: Participants will undergo one feeding by Aedes aegypti mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Aedes Aegypti n=8 Participants Four vector feeding: Participants will undergo four feedings by Aedes aegypti mosquitos each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Anopheles Gambiae n=8 Participants One vector feeding: Participants will undergo one feeding by Anopheles gambiae mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Anopheles Gambiae n=7 Participants Four vector feeding: Participants will undergo four feedings by Anopheles gambiae mosquitoes each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Lutzomyia Longipalpis n=8 Participants One vector feeding: Participants will undergo one feeding by Lutzomyia longipalpis and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Lutzomyia Longipalpis n=8 Participants Four vector feeding: Participants will undergo four feedings by Lutzomyia longipalpis each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding
Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups Neutrophils 30 minutes post bite	3 participants	NA participants Participants in Cohort B did not have a 30 minute time point per study protocol	2 participants	NA participants Participants in Cohort B did not have a 30 minute time point per study protocol	0 participants	NA participants Participants in Cohort B did not have a 30 minute time point per study protocol
Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups Mononuclear Cells 30 minutes post bite	3 participants	NA participants Participants in Cohort B did not have a 30 minute time point per study protocol	1 participants	NA participants Participants in Cohort B did not have a 30 minute time point per study protocol	3 participants	NA participants Participants in Cohort B did not have a 30 minute time point per study protocol
Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups Eosinophils 30 minutes post bite	4 participants	NA participants Participants in Cohort B did not have a 30 minute time point per study protocol	0 participants	NA participants Participants in Cohort B did not have a 30 minute time point per study protocol	0 participants	NA participants Participants in Cohort B did not have a 30 minute time point per study protocol
Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups Neutrophils 4 hours post bite	5 participants	6 participants	1 participants	3 participants	3 participants	3 participants
Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups Mononuclear Cells 4 hours post bite	5 participants	3 participants	0 participants	2 participants	2 participants	6 participants
Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups Eosinophils 4 hours post bite	3 participants	5 participants	0 participants	2 participants	1 participants	4 participants
Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups Neutrophils 48 hours post bite	NA participants Participants in Cohort A did not have a 48 hour time point per study protocol	1 participants	NA participants Participants in Cohort A did not have a 48 hour time point per study protocol	0 participants	NA participants Participants in Cohort A did not have a 48 hour time point per study protocol	0 participants
Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups Mononuclear Cells 48 hours post bite	NA participants Participants in Cohort A did not have a 48 hour time point per study protocol	8 participants	NA participants Participants in Cohort A did not have a 48 hour time point per study protocol	7 participants	NA participants Participants in Cohort A did not have a 48 hour time point per study protocol	8 participants
Participants With Local Skin Adaptive Immune Response After Multiple Exposures Over Time to Bites of Each of the Three Vector Groups Eosinophils 48 hours post bite	NA participants Participants in Cohort A did not have a 48 hour time point per study protocol	4 participants	NA participants Participants in Cohort A did not have a 48 hour time point per study protocol	1 participants	NA participants Participants in Cohort A did not have a 48 hour time point per study protocol	2 participants

Adverse Events

Single Exposure Cohort A: Aedes Aegypti

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Multiple Exposure Cohort B: Aedes Aegypti

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Single Exposure Cohort A: Anopheles Gambiae

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Multiple Exposure Cohort B: Anopheles Gambiae

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Single Exposure Cohort A: Lutzomyia Longipalpis

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Multiple Exposure Cohort B: Lutzomyia Longipalpis

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Single Exposure Cohort A: Aedes Aegypti n=15 participants at risk One vector feeding: Participants will undergo one feeding by Aedes aegypti mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Aedes Aegypti n=15 participants at risk Four vector feeding: Participants will undergo four feedings by Aedes aegypti mosquitos each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Anopheles Gambiae n=15 participants at risk One vector feeding: Participants will undergo one feeding by Anopheles gambiae mosquitoes and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Anopheles Gambiae n=14 participants at risk Four vector feeding: Participants will undergo four feedings by Anopheles gambiae mosquitoes each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding	Single Exposure Cohort A: Lutzomyia Longipalpis n=15 participants at risk One vector feeding: Participants will undergo one feeding by Lutzomyia longipalpis and then three biopsies on Day 0 were performed	Multiple Exposure Cohort B: Lutzomyia Longipalpis n=15 participants at risk Four vector feeding: Participants will undergo four feedings by Lutzomyia longipalpis each about 2 weeks apart, with the same vector type. 3 biopsy procedures were performed after the 4th and final feeding
Cardiac disorders Bradycardia	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Surgical and medical procedures Drainage at biopsy site	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Vascular disorders Hypotension	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Vascular disorders Systolic hypertension	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Cardiac disorders Tachycardia	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Cardiac disorders Palpitations	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Gastrointestinal disorders Vomiting	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
General disorders Fatigue	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
General disorders Non-cardiac chest pain	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
General disorders Feverish	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Infections and infestations Conjunctivitis	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Infections and infestations Gastroenteritis	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Infections and infestations Laryngitis	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Infections and infestations Latent Tuberculosis	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Infections and infestations Coryza	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Infections and infestations URI	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Injury, poisoning and procedural complications Erythema at biopsy site	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	13.3% 2/15 • Number of events 2 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Injury, poisoning and procedural complications Fractured metatarsal	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Musculoskeletal and connective tissue disorders Knee pain	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Musculoskeletal and connective tissue disorders Pain in hip	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Musculoskeletal and connective tissue disorders Shoulder pain	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Musculoskeletal and connective tissue disorders Muscle weakness	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Musculoskeletal and connective tissue disorders Foot pain	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Nervous system disorders Headache	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Psychiatric disorders Difficulty sleeping	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	14.3% 2/14 • Number of events 2 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	14.3% 2/14 • Number of events 2 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Respiratory, thoracic and mediastinal disorders Sinus pain	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Respiratory, thoracic and mediastinal disorders productive cough	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Respiratory, thoracic and mediastinal disorders dry cough	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	7.1% 1/14 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Skin and subcutaneous tissue disorders ecchymosis	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.
Skin and subcutaneous tissue disorders Rash	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/14 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	0.00% 0/15 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.	6.7% 1/15 • Number of events 1 • Monitoring for adverse events was over a 7 day period for all Cohort A groups. Monitoring for adverse events was over a 51 day period for all Cohort B groups.

Additional Information

Matthew J. Memoli, MD, MS

National Institutes of Health

Phone: 301-443-5971

Email: memolim@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place