Trial Outcomes & Findings for A Study to Assess the Efficacy and Safety of Mebendazole for the Treatment of Helminth Infections in Pediatric Participants (NCT NCT02034162)

NCT ID: NCT02034162

Last Updated: 2016-11-04

Results Overview

Cure is defined as a post-treatment egg count of zero in participants who had a positive egg count at baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

295 participants

Primary outcome timeframe

At Visit 3 (Day 19) of Double-blind treatment period

Results posted on

2016-11-04

Participant Flow

The study was conducted from 8-Dec-2014 to 3-Sep-2015. A total of 295 participants were enrolled and randomly assigned to study treatment; 278 participants completed the study. Of the 295 participants, 167 participants were reported with Ascaris lumbricoides infestation and 243 participants were reported with Trichuris trichiura infestation.

Of the 792 participants screened, a total of 295 were randomly assigned to study treatments, of which 278 completed the study. 17 participants were withdrawn from study with following reasons: Withdrawal by participant (12), Lost to follow-up (3), Physician decision (1) and Protocol violation (1).

Participant milestones

Participant milestones
Measure	Double-blind Placebo Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Open-label Mebendazole 500 mg Mebendazole 500-mg chewable tablet was administered in an open label manner at visit 3 (Day 19+/-2) followed up to Visit 5 (Day 7+/-1 from Visit 3).
Double-blind STARTED	146	149	0
Double-blind COMPLETED	137	141	0
Double-blind NOT COMPLETED	9	8	0
Open-label STARTED	0	0	278
Open-label COMPLETED	0	0	278
Open-label NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Double-blind Placebo Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).
Double-blind Lost to Follow-up	3	0
Double-blind Physician Decision	1	0
Double-blind Protocol Violation	0	1
Double-blind Withdrawal by Subject	5	7

Baseline Characteristics

A Study to Assess the Efficacy and Safety of Mebendazole for the Treatment of Helminth Infections in Pediatric Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-blind Placebo n=146 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=149 Participants Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Total n=295 Participants Total of all reporting groups
Age, Continuous	7.7 years STANDARD_DEVIATION 3.09 • n=5 Participants	7.9 years STANDARD_DEVIATION 3.27 • n=7 Participants	7.8 years STANDARD_DEVIATION 3.18 • n=5 Participants
Sex: Female, Male Female	74 Participants n=5 Participants	78 Participants n=7 Participants	152 Participants n=5 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	71 Participants n=7 Participants	143 Participants n=5 Participants
Region of Enrollment ETHIOPIA	127 participants n=5 Participants	128 participants n=7 Participants	255 participants n=5 Participants
Region of Enrollment RWANDA	19 participants n=5 Participants	21 participants n=7 Participants	40 participants n=5 Participants

PRIMARY outcome

Timeframe: At Visit 3 (Day 19) of Double-blind treatment period

Population: The intent-to-treat (ITT) analysis set included all randomized participants with a pretreatment stool sample positive for 1 or more worms of interest. Here 'N' signifies number of participants analysed for this outcome measure.

Cure is defined as a post-treatment egg count of zero in participants who had a positive egg count at baseline.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=81 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=86 Participants Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole: Group 3 (7 to 16 Years) Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Cure Rate for Ascaris Lumbricoides at the End of Double-blind Treatment Period	11.1 percentage of participants Interval 5.2 to 20.1	83.7 percentage of participants Interval 74.2 to 90.8	—

PRIMARY outcome

Timeframe: At Visit 3 (Day 19) of Double-blind treatment period

Population: The ITT analysis set included all randomized participants with a pretreatment stool sample positive for 1 or more worms of interest. Here 'N' signifies number of participants analysed for this outcome measure.

Cure is defined as a post-treatment egg count of zero in participants who had a positive egg count at baseline.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=119 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=124 Participants Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole: Group 3 (7 to 16 Years) Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Cure Rate for Trichuris Trichiura at the End of Double-blind Treatment Period	7.6 percentage of participants Interval 3.5 to 13.9	33.9 percentage of participants Interval 25.6 to 42.9	—

PRIMARY outcome

Timeframe: Up to Visit 3 (Day 19 +/-2)

Population: The safety analysis set consisted of all randomized participants who received 1 dose of study agent (mebendazole or placebo) at baseline. Here 'N' signifies number of participants analysed for this outcome measure.

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=140 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=144 Participants Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole: Group 3 (7 to 16 Years) Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Number of Participants Reporting Treatment Emergent Adverse Event (TEAE) in Double-Blind Treatment Period	8 participants	9 participants	—

PRIMARY outcome

Timeframe: At Visit 3 (Day 19+/-2) followed up to Visit 5 (Day 7+/-1 from Visit 3)

Population: The open-label follow-up safety analysis set consisted of all randomized participants who received a 500-mg chewable tablet of mebendazole at Visit 3. Here 'N' signifies number of participants analysed for this outcome measure.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=278 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole: Group 3 (7 to 16 Years) Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Number of Participants Reporting Treatment Emergent Adverse Event (TEAE) in Open-Label Treatment Period	7 participants	—	—

SECONDARY outcome

Timeframe: Baseline and Day 19 (Visit 3) at the End of Double-blind Treatment Period

Percent egg count reduction is calculated as average egg count at end of treatment period of a treatment group minus average egg count at baseline of the treatment group divided by average egg count at baseline of the treatment group.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=81 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=86 Participants Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole: Group 3 (7 to 16 Years) Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Egg Count Reduction Rate (Percent) for Ascaris Lumbricoides Infestation at the End of Double-blind Treatment Period	-19.2 percent change in egg count 20684.03	-97.9 percent change in egg count 23476.82	—

SECONDARY outcome

Timeframe: Baseline and Day 19 (Visit 3) at the End of Double-blind Treatment Period

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=119 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=124 Participants Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole: Group 3 (7 to 16 Years) Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Egg Count Reduction Rate (Percent) for Trichuris Trichiura Infestation at the End of Double-blind Treatment Period	-10.5 percent change in egg count 930.05	-59.7 percent change in egg count 1256.22	—

SECONDARY outcome

Timeframe: Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)

Population: Pharmacokinetic (PK) population included all randomized participants who received at least 1 dose of the study drug and had valid pharmacokinetic profile. Here 'N' signifies number of participants analysed for this outcome measure.

The Cmax is the maximum plasma concentration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=22 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=12 Participants Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole: Group 3 (7 to 16 Years) n=10 Participants Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Maximum Plasma Concentration (Cmax) of Mebendazole	210.0 nanogram per Milliliters (ng/mL) Standard Deviation 212.0	49.9 nanogram per Milliliters (ng/mL) Standard Deviation 26.8	34.2 nanogram per Milliliters (ng/mL) Standard Deviation 13.8

SECONDARY outcome

Timeframe: Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)

Population: PK population included all randomized participants who received at least 1 dose of the study drug and had valid pharmacokinetic profile. Here 'N' signifies number of participants analysed for this outcome measure.

The Time to Reach Maximum Plasma Concentration (Tmax) is time to reach the maximum plasma concentration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=22 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=12 Participants Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole: Group 3 (7 to 16 Years) n=10 Participants Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Time to Reach Maximum Plasma Concentration (Tmax) of Mebendazole	2.5 hours Interval 1.0 to 8.0	2 hours Interval 0.98 to 3.0	3 hours Interval 1.0 to 8.0

SECONDARY outcome

Timeframe: Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)

The (AUC8h) is the area under the plasma concentration-time curve from time 0 to 8 hours Post-dose.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=21 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=9 Participants Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole: Group 3 (7 to 16 Years) n=10 Participants Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours (AUC8h) of Mebendazole	697 nanogram hour per Milliliters(ng*h/mL) Standard Deviation 367	242 nanogram hour per Milliliters(ng*h/mL) Standard Deviation 139	182 nanogram hour per Milliliters(ng*h/mL) Standard Deviation 66.3

SECONDARY outcome

Timeframe: Predose, 1, 2, 3, 5, 8 and 24 hours postdose at visit 4 (Day 20; 1 day after Visit 3)

The (AUC \[0-last\]) is the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration.

Outcome measures

Outcome measures
Measure	Double-blind Placebo n=22 Participants Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=12 Participants Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Mebendazole: Group 3 (7 to 16 Years) n=10 Participants Group 3 represents pharmacokinetic analysis set which included participants with age group 7 to 16 years and received Mebendazole 500 mg.
Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-last) of Mebendazole	1320 ng*h/mL Standard Deviation 844	416 ng*h/mL Standard Deviation 215	387 ng*h/mL Standard Deviation 190

Adverse Events

Double-blind Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Double-blind Mebendazole 500 mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

OL Mebendazole 500 mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

DIRECTOR CLINICAL LEAD

Janssen R&D US

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Double-blind Placebo n=140 participants at risk Placebo Comparator: Placebo. Matching placebo was administered as a single-dose chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	Double-blind Mebendazole 500 mg n=144 participants at risk Experimental: Mebendazole. Mebendazole was administered as a single 500-mg chewable tablet in a double-blind manner at the baseline visit (Day 1) followed up to Visit 3 (Day 19+/-2).	OL Mebendazole 500 mg n=278 participants at risk Mebendazole 500-mg chewable tablet was administered in an open label manner at visit 3 (Day 19+/-2) followed up to Visit 5 (Day 7+/-1 from Visit 3).
Eye disorders Night Blindness	0.71% 1/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Gastrointestinal disorders Abdominal Distension	0.71% 1/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	1.4% 2/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Gastrointestinal disorders Abdominal Pain	0.71% 1/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.69% 1/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.36% 1/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Gastrointestinal disorders Diarrhoea	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.72% 2/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Gastrointestinal disorders Vomiting	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.36% 1/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Infections and infestations Conjunctivitis	0.71% 1/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Infections and infestations Conjunctivitis Bacterial	0.71% 1/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Infections and infestations Gastroenteritis	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.69% 1/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Infections and infestations Malaria	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.36% 1/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Infections and infestations Nasopharyngitis	1.4% 2/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.69% 1/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Infections and infestations Pneumonia	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.36% 1/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Infections and infestations Tinea Infection	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.69% 1/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Infections and infestations Tonsillitis	0.71% 1/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Injury, poisoning and procedural complications Soft Tissue Injury	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.36% 1/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Metabolism and nutrition disorders Vitamin A Deficiency	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.69% 1/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Nervous system disorders Headache	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.36% 1/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Respiratory, thoracic and mediastinal disorders Cough	1.4% 2/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.69% 1/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.36% 1/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])
Skin and subcutaneous tissue disorders Rash Pruritic	0.00% 0/140 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.69% 1/144 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])	0.00% 0/278 • Up to visit 5 (Day 26, 7+/-1 days after Visit 3 [Day 19+/-2])