Trial Outcomes & Findings for Pharmacokinetic, Safety, Tolerability, and Clinical Effect of Topical Umeclidinium in Primary Axillary Hyperhidrosis (NCT NCT02563899)

NCT ID: NCT02563899

Last Updated: 2018-10-11

Results Overview

Pharmacokinetic blood sampling was done at the following time points: Day 12 (pre-dose), Day 13 (pre-dose), Day 14 (pre-dose), Day 15 (3 hours \[h\], 6 h, 9 h, 10 h, 12 h, 16 h, and 24 h following the Day 14 dose), Day 16 (36 h and 48 h following the Day 14 dose). Approximately 3 ml of blood was taken at each timepoint. Mean and standard deviation of the umeclidinium concentration was reported. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 28 participants
• Primary outcome timeframe: Day 12 to Day 16
• Results posted on: 2018-10-11

Participant Flow

The study conducted between 23 November 2015 to 25 February 2016. The data for population pharmacokinetic (PK) analysis was pooled from the earlier two studies including LHH117157 (NCT01934153) (6 participants from Cohort B) and AC4112008 (NCT01110018) (9 participants) with the data of the current study.

A total of 28 participants randomized in this study. Because of a system configuration error, randomization numbers were assigned to 5 screen failure participants. However, these participants did not enter the study and not dosed, remaining 23 participants (18- Umeclidinium; 5- Placebo) included in Full Analysis Population.

Participant milestones

Measure	202093: Umeclidinium, 2 mg/cm^2 of 1.85%, OD Participants topically applied Umeclidinium 2 milligram per square centimeter (mg/cm\^2) of the 1.85%, administered once daily (OD) to both axillae, at night before going to bed for 14 days.	202093: Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participant received single dose of treatment in the following order of intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium was administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% weight/ weight (w/w) solution umeclidinium (equivalent to a 2.2% umeclidinium bromide solution) applied to 40 centimeter squared (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active umeclidinium of 3.06 mg).
Overall Study STARTED	18	5	10	6
Overall Study COMPLETED	17	5	9	6
Overall Study NOT COMPLETED	1	0	1	0

Reasons for withdrawal

Measure	202093: Umeclidinium, 2 mg/cm^2 of 1.85%, OD Participants topically applied Umeclidinium 2 milligram per square centimeter (mg/cm\^2) of the 1.85%, administered once daily (OD) to both axillae, at night before going to bed for 14 days.	202093: Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participant received single dose of treatment in the following order of intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium was administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% weight/ weight (w/w) solution umeclidinium (equivalent to a 2.2% umeclidinium bromide solution) applied to 40 centimeter squared (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active umeclidinium of 3.06 mg).
Overall Study Protocol Violation	1	0	0	0
Overall Study Withdrawal by Subject	0	0	1	0

Baseline Characteristics

Pharmacokinetic, Safety, Tolerability, and Clinical Effect of Topical Umeclidinium in Primary Axillary Hyperhidrosis

Baseline characteristics by cohort

Measure	202093: Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	202093: Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 n=10 Participants Each participant received single dose of treatment in the following order of intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B n=6 Participants A single dose of topically applied \[14C\] umeclidinium was administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution umeclidinium (equivalent to a 2.2% umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active umeclidinium of 3.06 mg).	Total n=39 Participants Total of all reporting groups
Age, Customized 19 to 64 Years	18 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants	6 Participants n=4 Participants	39 Participants n=21 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	13 Participants n=21 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants	6 Participants n=4 Participants	26 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants	6 Participants n=4 Participants	37 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 12 to Day 16

Population: Pharmacokinetic Concentration Population defined as all participants in the Safety population for whom at least one pharmacokinetic sample was obtained and analyzed. Safety Population is defined as all participants who received at least one dose of a study drug in this study (202093)

Pharmacokinetic blood sampling was done at the following time points: Day 12 (pre-dose), Day 13 (pre-dose), Day 14 (pre-dose), Day 15 (3 hours [h], 6 h, 9 h, 10 h, 12 h, 16 h, and 24 h following the Day 14 dose), Day 16 (36 h and 48 h following the Day 14 dose). Approximately 3 ml of blood was taken at each timepoint. Mean and standard deviation of the umeclidinium concentration was reported. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Mean Plasma Concentration After Repeat Dosing of Umeclidinium DAY 12, Pre-dose	33.09 picogram per millilitre (pg/ml) Standard Deviation 23.206	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium DAY 13, Pre-dose	29.86 picogram per millilitre (pg/ml) Standard Deviation 20.981	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium DAY 14, Pre-dose	41.22 picogram per millilitre (pg/ml) Standard Deviation 42.465	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium Day 14, 3 h	42.72 picogram per millilitre (pg/ml) Standard Deviation 57.839	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium Day 14, 6 h	53.68 picogram per millilitre (pg/ml) Standard Deviation 69.157	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium Day 14, 9 h	57.32 picogram per millilitre (pg/ml) Standard Deviation 74.719	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium Day 14, 10 h	57.24 picogram per millilitre (pg/ml) Standard Deviation 77.945	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium Day 14, 12 h	50.72 picogram per millilitre (pg/ml) Standard Deviation 63.468	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium Day 14, 16 h	35.42 picogram per millilitre (pg/ml) Standard Deviation 37.727	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium Day 14, 24 h	31.50 picogram per millilitre (pg/ml) Standard Deviation 29.458	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium Day 14, 36 h	30.76 picogram per millilitre (pg/ml) Standard Deviation 46.979	—	—	—
Mean Plasma Concentration After Repeat Dosing of Umeclidinium Day 14, 48 h	14.28 picogram per millilitre (pg/ml) Standard Deviation 14.739	—	—	—

PRIMARY outcome

Timeframe: Day 14 (pre-dose), Day 15 (3 h, 6 h, 9 h, 10 h, 12 h, 16 h, and 24 h following the Day 14 dose), Day 16 (36 h and 48 h following the Day 14 dose)

Population: Pharmacokinetic Concentration Population. Only those participants available at the specified time points were analyzed.

Pharmacokinetic blood sampling was done at Day 14 (pre-dose), Day 15 (3 h, 6 h, 9 h, 10 h, 12 h, 16 h, and 24 h following the Day 14 dose), Day 16 (36 h and 48 h following the Day 14 dose). Cmax and Ctau was determined directly from the concentration-time data.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) After Repeat Dosing of Umeclidinium Cmax, Day 14	44.79 pg/mL Geometric Coefficient of Variation 175.27	—	—	—
Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) After Repeat Dosing of Umeclidinium Ctau, Day 12	27.94 pg/mL Geometric Coefficient of Variation 63.30	—	—	—
Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) After Repeat Dosing of Umeclidinium Ctau, Day 13	25.81 pg/mL Geometric Coefficient of Variation 55.40	—	—	—
Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) After Repeat Dosing of Umeclidinium Ctau, Day 14	39.60 pg/mL Geometric Coefficient of Variation 87.68	—	—	—
Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) After Repeat Dosing of Umeclidinium Ctau, Day 15	29.63 pg/mL Geometric Coefficient of Variation 66.76	—	—	—

PRIMARY outcome

Timeframe: Day 14 to Day 16

Population: Pharmacokinetic Concentration Population. Only those participants available at the specified time points were analyzed.

Pharmacokinetic blood sampling was done at Day 14 (pre-dose), Day 15 (3 h, 6 h, 9 h, 10 h, 12 h, 16 h, and 24 h following the Day 14 dose), Day 16 (36 h and 48 h following the Day 14 dose). Tmax was determined directly from the concentration-time data.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=14 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Mean Time to Reach Cmax (Tmax) of Umeclidinium After Repeat Dosing	10.25 h Standard Deviation 7.985	—	—	—

PRIMARY outcome

Timeframe: Day 14 to Day 16

Population: Pharmacokinetic Concentration Population

Pharmacokinetic blood sampling was done at Day 14 (pre-dose), Day 15 (3 h, 6 h, 9 h, 10 h, 12 h, 16 h, and 24 h following the Day 14 dose), Day 16 (36 h and 48 h following the Day 14 dose). Derivation of lambda-Z was planned. However, the parameter could not be derived for any of the participant included in the study because of insufficient data in the elimination phase (< 3 data points, coefficient of determination (R^2) was not adequate).

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 14 to Day 16

Population: Pharmacokinetic Concentration Population

Pharmacokinetic blood sampling was done at Day 14 (pre-dose), Day 15 (3 h, 6 h, 9 h, 10 h, 12 h, 16 h, and 24 h following the Day 14 dose), Day 16 (36 h and 48 h following the Day 14 dose). Derivation of t1/2 was planned. However, the parameter could not be derived for any of the participant included in the study because of insufficient data in the elimination phase (< 3 data points, coefficient of determination (R^2) was not adequate).

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 14 to Day 16

Population: Pharmacokinetic Concentration Population. Only those participants available at the specified time points were analyzed.

Pharmacokinetic blood sampling was done at Day 14 (pre-dose), Day 15 (3 h, 6 h, 9 h, 10 h, 12 h, 16 h, and 24 h following the Day 14 dose), Day 16 (36 h and 48 h following the Day 14 dose). Calculated using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. Geometric mean of log-transformed values of AUC were reported.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=16 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Mean Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments (0-t) and AUC Over the Dosing Interval (0-tau) of Umeclidinium After Repeat Dosing AUC(0-t)	1036.90 h*pg/mL Geometric Coefficient of Variation 142.63	—	—	—
Mean Area Under the Concentration-time Curve (AUC) From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration Across All Treatments (0-t) and AUC Over the Dosing Interval (0-tau) of Umeclidinium After Repeat Dosing AUC(0-tau)	703.67 h*pg/mL Geometric Coefficient of Variation 108.61	—	—	—

PRIMARY outcome

Timeframe: Day 12 to Day 16

Population: Pharmacokinetic Concentration Populations from studies 202093 (16 participants), AC4112008 (9 participants) and LHH117157 (6 participants) were pooled to population Pk parameter analysis.

Pharmacokinetic blood sampling was done at Pre-dose, 3h, 6h, 9h, 10h, 12h, 16h, 24h, 36h, 48h of current study (202093), pre-dose, 10, 20, 30, 32, 35, 45 minute, 1h, 2h, 4h, 6h, 8h, 12h, 16h, 24h, 36h, 48h for study AC4112008, and Pre-dose, 2h, 4h, 5h, 6h, 8h, 8.5h, 9h, 9.5h, 10h, 11h, 12h, 13h, 14h, 16h, 24h, 30h, 36h, 48h, 72h for study number LHH117157. Plasma umeclidinium concentration time data following administration to axilae of hyperhidrosis participants from the current study (202093) were pooled with data from the occluded axilla cohort from study LHH117157 and the IV infusion data from study AC4112008 in order modify the existing population PK model for dermal umeclidinium. Plasma concentration-time data was subjected to nonlinear mixed effects modelling using the program NONMEM to develop a population PK model. The data for V1 and V2 was reported as mean (estimate) with relative standard error (RSE). RSE= (Standard error of the estimate/ Final parameter estimate) X 100.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=31 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Composite Population Pharmacokinetics Parameter: Volume of Distribution in Central Compartment (V1) and Volume of Distribution in Peripheral Compartment (V2) V1	7.44 Litre (L) Standard Error 9.65	—	—	—
Composite Population Pharmacokinetics Parameter: Volume of Distribution in Central Compartment (V1) and Volume of Distribution in Peripheral Compartment (V2) V2	333 Litre (L) Standard Error 22.6	—	—	—

PRIMARY outcome

Timeframe: Day 12 to Day 16

Population: Pharmacokinetic Concentration Populations from studies 202093 (16 participants), AC4112008 (9 participants) and LHH117157 (6 participants) were pooled to population Pk parameter analysis.

Pharmacokinetic blood sampling was done at Pre-dose, 3h, 6h, 9h, 10h, 12h, 16h, 24h, 36h, 48h of current study (202093), pre-dose, 10, 20, 30, 32, 35, 45 minute, 1h, 2h, 4h, 6h, 8h, 12h, 16h, 24h, 36h, 48h for study AC4112008, and Pre-dose, 2h, 4h, 5h, 6h, 8h, 8.5h, 9h, 9.5h, 10h, 11h, 12h, 13h, 14h, 16h, 24h, 30h, 36h, 48h, 72h for study number LHH117157. Plasma umeclidinium concentration time data following administration to axilae of hyperhidrosis participants from the current study (202093) were pooled with data from the occluded axilla cohort from study LHH117157 and the IV infusion data from study AC4112008 in order modify the existing population PK model for dermal umeclidinium. Plasma concentration-time data was subjected to nonlinear mixed effects modelling using the program NONMEM to develop a population PK model. The data for CL and Q was reported as mean (estimate) with RSE. RSE= (Standard error of the estimate/ Final parameter estimate) X 100.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=31 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Composite Population Pharmacokinetics Parameter: Elimination Clearance (CL) and Inter-compartmental Clearance (Q) CL	53.2 L/h Standard Error 11.1	—	—	—
Composite Population Pharmacokinetics Parameter: Elimination Clearance (CL) and Inter-compartmental Clearance (Q) Q	43.1 L/h Standard Error 24.6	—	—	—

PRIMARY outcome

Timeframe: Day 12 to Day 16

Population: Pharmacokinetic Concentration Populations from studies 202093 (16 participants), AC4112008 (9 participants) and LHH117157 (6 participants) were pooled to population Pk parameter analysis.

Pharmacokinetic blood sampling was done at Pre-dose, 3h, 6h, 9h, 10h, 12h, 16h, 24h, 36h, 48h of current study (202093), pre-dose, 10, 20, 30, 32, 35, 45 minute, 1h, 2h, 4h, 6h, 8h, 12h, 16h, 24h, 36h, 48h for study AC4112008, and Pre-dose, 2h, 4h, 5h, 6h, 8h, 8.5h, 9h, 9.5h, 10h, 11h, 12h, 13h, 14h, 16h, 24h, 30h, 36h, 48h, 72h for study number LHH117157. Plasma umeclidinium concentration time data following administration to axilae of hyperhidrosis participants from the current study (202093) were pooled with data from the occluded axilla cohort from study LHH117157 and the IV infusion data from study AC4112008 in order modify the existing population PK model for dermal umeclidinium. Plasma concentration-time data was subjected to nonlinear mixed effects modelling using the program NONMEM to develop a population PK model. The data for Ka was reported as mean (estimate) with RSE. RSE= (Standard error of the estimate/ Final parameter estimate) X 100.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=31 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Composite Population Pharmacokinetics Parameter: Absorption Rate Constant (Ka)	0.012 1/h Standard Error 48.6	—	—	—

PRIMARY outcome

Timeframe: Day 12 to Day 16

Population: Pharmacokinetic Concentration Populations from studies 202093 (16 participants), AC4112008 (9 participants) and LHH117157 (6 participants) were pooled to population PK parameter analysis.

Pharmacokinetic blood sampling was done at Pre-dose, 3h, 6h, 9h, 10h, 12h, 16h, 24h, 36h, 48h of current study (202093), pre-dose, 10, 20, 30, 32, 35, 45 minute, 1h, 2h, 4h, 6h, 8h, 12h, 16h, 24h, 36h, 48h for study AC4112008, and Pre-dose, 2h, 4h, 5h, 6h, 8h, 8.5h, 9h, 9.5h, 10h, 11h, 12h, 13h, 14h, 16h, 24h, 30h, 36h, 48h, 72h for study number LHH117157. Plasma umeclidinium concentration time data following administration to axilae of hyperhidrosis participants from the current study (202093) were pooled with data from the occluded axilla cohort from study LHH117157 and the IV infusion data from study AC4112008 in order modify the existing population PK model for dermal umeclidinium. Plasma concentration-time data was subjected to nonlinear mixed effects modelling using the program NONMEM to develop a population PK model. The data for FA and F2 (FIXED) was reported as mean (estimate) with RSE. RSE= (Standard error of the estimate/ Final parameter estimate) x 100.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=31 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Composite Population Pharmacokinetics Parameter: Absolute Plasma Bioavailability Following Administration to Axilae (FA) Fraction of the Bioavailable Drug Absorbed Through a Zero Order Process (F2 [FIXED]) FA	-5.05 Ratio Standard Error 3.15	—	—	—
Composite Population Pharmacokinetics Parameter: Absolute Plasma Bioavailability Following Administration to Axilae (FA) Fraction of the Bioavailable Drug Absorbed Through a Zero Order Process (F2 [FIXED]) F2	-2 Ratio Standard Error 0	—	—	—

PRIMARY outcome

Timeframe: Day 12 to Day 16

Population: Pharmacokinetic Concentration Populations from studies 202093 (16 participants), AC4112008 (9 participants) and LHH117157 (6 participants) were pooled to population PK parameter analysis.

Pharmacokinetic blood sampling was done at Pre-dose, 3h, 6h, 9h, 10h, 12h, 16h, 24h, 36h, 48h of current study (202093), pre-dose, 10, 20, 30, 32, 35, 45 minute, 1h, 2h, 4h, 6h, 8h, 12h, 16h, 24h, 36h, 48h for study AC4112008, and Pre-dose, 2h, 4h, 5h, 6h, 8h, 8.5h, 9h, 9.5h, 10h, 11h, 12h, 13h, 14h, 16h, 24h, 30h, 36h, 48h, 72h for study number LHH117157. Plasma umeclidinium concentration time data following administration to axilae of hyperhidrosis participants from the current study (202093) were pooled with data from the occluded axilla cohort from study LHH117157 and the IV infusion data from study AC4112008 in order modify the existing population PK model for dermal umeclidinium. Plasma concentration-time data was subjected to nonlinear mixed effects modelling using the program NONMEM to develop a population PK model. The data for ALAG1 was reported as mean (estimate) with RSE. RSE= (Standard error of the estimate/ Final parameter estimate) x 100.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=31 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Composite Population Pharmacokinetics Parameter: Duration of the Zero Order Process and Lag Time for the First Order Absorption Process (ALAG1)	2.56 h Standard Error 26.5	—	—	—

PRIMARY outcome

Timeframe: Over a period of 28 days

Population: Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report AEs.

AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 n=10 Participants Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B n=6 Participants A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) Any AE	9 Participants	2 Participants	6 Participants	2 Participants
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) Any SAE	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 28

Population: Safety Population is defined as all participants who received at least one dose of a study drug in this study (202093).

Single 12-lead ECGs was obtained at Day 1, Day 14 and Day 28 during the study. The standard ECG criteria of potential clinical importance were 1) absolute QTc Interval, > 450 milliseconds (msec), 2) absolute PR Interval, <110 msec, 3) absolute QRS Interval, < 75 msec and 4) increase from baseline in QTc > 60 msec. The number of participants with potentially clinically significant ECG findings at any visit were reported.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Number of Participants With Abnormal Values of Potential Clinical for Electrocardiogram (ECG) Low PR interval	0 Participants	1 Participants	—	—
Number of Participants With Abnormal Values of Potential Clinical for Electrocardiogram (ECG) Low QRS	3 Participants	0 Participants	—	—
Number of Participants With Abnormal Values of Potential Clinical for Electrocardiogram (ECG) High QRS	2 Participants	0 Participants	—	—
Number of Participants With Abnormal Values of Potential Clinical for Electrocardiogram (ECG) High QTcB	1 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Up to day 28

Population: Safety Population is defined as all participants who received at least one dose of a study drug in this study (202093).

The clinical chemistry parameters analyzed were albumin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bicarbonate, blood urea nitrogen, calcium, chloride, creatinine, gamma glutamyl transferase, glucose, potassium, sodium, total and direct bilirubin, total protein, uric acid. Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important clinical chemistry findings at any visit were reported.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance at Any Time on Treatment High, alanine aminotransferase	1 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance at Any Time on Treatment High, aspartate aminotransferase	1 Participants	1 Participants	—	—
Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance at Any Time on Treatment High, glucose	1 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Up to Day 28

Population: Safety Population is defined as all participants who received at least one dose of a study drug in this study (202093).

The hematology parameters analyzed were basophils, eosinophils, erythrocyte mean corpuscular hemoglobin concentration, erythrocyte mean corpuscular hemoglobin, erythrocyte mean corpuscular volume, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils, platelets, and reticulocytes. Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important hematology findings at any visit were reported.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Number of Participants With Clinical Hematology Abnormalities of Potential Clinical Importance at Any Time on Treatment. Low, Neutrophils	1 Participants	0 Participants	—	—
Number of Participants With Clinical Hematology Abnormalities of Potential Clinical Importance at Any Time on Treatment. High, Hematocrit	1 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Up to Day 28

Population: Safety Population is defined as all participants who received at least one dose of a study drug in this study (202093).

The urinalysis parameters analyzed were specific gravity, pH, glucose, protein, blood and ketones by dipstick, microscopic examination. Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important urinalysis findings at any visit were reported.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Number of Participants With Urinalysis Abnormalities of Potential Clinical Importance at Any Time on Treatment	1 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Up to 28 days

Population: Safety Population is defined as all participants who received at least one dose of a study drug in this study (202093).

The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (<85 and >160 millimeter of mercury [mmHg]), diastolic blood pressure (<45 and >100 mmHg) and heart rate (<40 and >110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Number of Participants With Abnormal Values of Potential Clinical for Vital Signs	1 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Days 1, 2, 4, 5, 6, 7, 8, 9, 10, 13, 14, 15, 16, and 23

Population: Safety Population is defined as all participants who received at least one dose of a study drug in this study (202093).

The investigator or designated evaluator assessed skin tolerability at each visit using the 5-point tolerability scale. Tolerability of the topical application was assessed and scored as, 0- none (no evidence of local intolerance), 1-mild (minimal erythema and/or edema, slight glazed appearance), 2-moderate (definite erythema and/or edema with peeling and/or cracking but needs no adaptation of posology), 3-severe (erythema, edema glazing with fissures, few vesicles or papules), 4- very severe (strong reaction spreading beyond the treated area, bullous reaction, erosions).

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 2, Mild, n= 18, 5	2 Participants	2 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 4, Moderate, n= 18, 5	1 Participants	0 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 5, Mild, n= 17, 5	2 Participants	0 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 6, Mild, n= 17, 5	2 Participants	1 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 7, Mild, n= 18, 5	2 Participants	0 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 8, Mild, n= 15, 5	3 Participants	0 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 1, Mild, n= 18, 5	2 Participants	0 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 9, Mild, n= 16, 5	1 Participants	0 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 10, Mild, n= 16, 5	0 Participants	1 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 13, Mild, n= 17, 5	2 Participants	1 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 13, Moderate, n= 17, 5	1 Participants	0 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 14, Mild, n= 17, 5	2 Participants	0 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 15, Mild, n= 17, 5	1 Participants	0 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 16, Mild, n= 17, 5	1 Participants	1 Participants	—	—
Number of Participants With Local Tolerability Assessment Score Over 28 Days Day 23, Mild, n= 17, 5	2 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Baseline (Pre-dose, Day 1) and Day 15

Population: Full Analysis population comprised of participants receiving study medication and having at least 1 post baseline visit. Only those participants available at the specified time points were analyzed.

Amount of sweat produced was determined by gravimetry analysis for axilla. Filter paper in a sealed container was weighed. After drying the axillary surface, the filter paper was removed from the container and applied to the axilla. The paper was covered with plastic wrap and tape around the edges with paper tape. The filter paper was left in contact with the axilla for a period of 5 minutes as measured by a stopwatch. The filter paper was then replaced in the sealed container and re-weighed. Rate of sweat production was calculated in milligrams/minute (mg/min). Participants remained at rest for 20-30 minute before the measurements in order to reduce external interference. Measurements were carried out in a climate-controlled environment (21-24°C). Assessments conducted at Day 1, Pre-dose time point (average pre-dose measurements for both left and right measurements) were considered as Baseline values. Change from baseline was calculated as Day 15 value minus Baseline value.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=17 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Change From Baseline in Amount of Sweat Produced at Day 15	-0.0571 mg/ min Standard Deviation 0.09402	-0.0164 mg/ min Standard Deviation 0.01735	—	—

SECONDARY outcome

Timeframe: Baseline (Pre-dose, Day 1) and Day 15

Population: Full Analysis population. Only those participants available at the specified time points were analyzed.

Amount of sweat produced was determined by gravimetry analysis for axilla. Filter paper in a sealed container was weighed. After drying the axillary surface, the filter paper was removed from the container and applied to the axilla. The paper was covered with plastic wrap and tape around the edges with paper tape. The filter paper was left in contact with the axilla for a period of 5 minutes as measured by a stopwatch. The filter paper was then replaced in the sealed container and re-weighed. Rate of sweat production was calculated in milligrams/minute. Assessments conducted at Day 1, Pre-dose time point (average pre-dose measurements for both left and right measurements) were considered as Baseline values. Percent change from Baseline= 100 x ( Day 15 value - Baseline value) / Baseline value. The percentage of participants with cutpoints (-30%, -50, -75%) for percent change from Baseline in sweat production were presented.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=18 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Percentage of Participants With Cut-points for Percent Change From Baseline in Sweat Production at Day 15 <=-30%	59 Percentage of participants	60 Percentage of participants	—	—
Percentage of Participants With Cut-points for Percent Change From Baseline in Sweat Production at Day 15 <=-50%	41 Percentage of participants	40 Percentage of participants	—	—
Percentage of Participants With Cut-points for Percent Change From Baseline in Sweat Production at Day 15 <=-75%	29 Percentage of participants	20 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline (Pre-dose, Day 1) and Day 15

Population: Full Analysis population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

The HDSS is a 4-point scale which used to assess the impact of disease. The scores were define as, 1- My (underarm) sweating is never noticeable and never interferes with my daily Activities; 2- My (underarm) sweating is tolerable but sometimes interferes with my daily activities; 3- My (underarm) sweating is barely tolerable and frequently interferes with my daily activities; 4- My (underarm) sweating is intolerable and always interferes with my daily activities. Average score of both left and right underarms were used for analysis. The possible average score range from 1 (minimum) to 4 (maximum). The reduction in score on the scale presents betterment and increase in the score represents worsening. Assessments conducted at Day 1, pre-dose time point (average pre-dose measurements for both left and right underarm measurements) were considered as Baseline values. Change from baseline was calculated as Day 15 Visit Value minus Baseline values.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=17 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Change in Hyperhidrosis Disease Severity Scale (HDSS) at Day 15	-1.4 Score on Scale Standard Error 1.00	-0.6 Score on Scale Standard Error 0.89	—	—

SECONDARY outcome

Timeframe: Baseline (Pre-dose, Day 1) and Day 15

Population: Full Analysis population. Only those participants available at the specified time points were analyzed.

HDSS is a 4-point scale which used to assess the impact of disease. The scores are define as, 1- My (underarm) sweating is never noticeable and never interferes with my daily Activities; 2- My (underarm) sweating is tolerable but sometimes interferes with my daily activities; 3- My (underarm) sweating is barely tolerable and frequently interferes with my daily activities; 4- My (underarm) sweating is intolerable and always interferes with my daily activities. Average score of both left and right underarms were used for analysis. The possible average score range from 1 (minimum) to 4 (maximum). Increase in score on scale represents worsening. Assessments conducted at Day 1, pre-dose time point (average pre-dose measurements for both left and right underarm measurements) were considered as Baseline values. Change from baseline was calculated as Day 15 Visit Value minus Baseline values. Percentage of participants with 2-point decrease from Baseline to Day 15 in HDSS score were reported.

Outcome measures

Measure	Umeclidinium, 2 mg/cm^2 of 1.85%, OD n=17 Participants Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	Vehicle n=5 Participants Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution Umeclidinium (equivalent to a 2.2% Umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active Umeclidinium of 3.06 mg).
Percentage of Participants With 2-point Decrease From Baseline to Day 15 in HDSS Score	47 Percentage of participants	20 Percentage of participants	—	—

Adverse Events

202093:Umeclidinium

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

202093:Vehicle

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

AC4112008: GSK573719

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

LHH117157: Cohort B

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	202093:Umeclidinium n=18 participants at risk Participants topically applied Umeclidinium 2 mg/cm\^2 of the 1.85% formulation, administered OD to both axillae, at night before going to bed for 14 days.	202093:Vehicle n=5 participants at risk Participants topically applied vehicle, OD to both axillae, at night before going to bed for 14 days.	AC4112008: GSK573719 n=10 participants at risk Each participants received single dose of treatment in the following order intravenous GSK573719 20 µg followed by oral GSK573719 1000 μg followed by intravenous GSK573719 50 µg, followed by inhaled GSK573719 1000 μg followed by intravenous GSK573719 65 µg in period 1, 2, 3, 4 and 5 respectively. The washout was of 5 days between two consecutive periods.	LHH117157: Cohort B n=6 participants at risk A single dose of topically applied \[14C\] umeclidinium administered to the occluded axilla. The dose to be administered was 165 mg of a 1.85% (w/w) solution umeclidinium (equivalent to a 2.2% umeclidinium bromide solution) applied to 40 (cm\^2) surface area of occluded axilla (resulting in a calculated net amount of active umeclidinium of 3.06 mg).
Skin and subcutaneous tissue disorders Blister	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
General disorders Application site pain	16.7% 3/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
General disorders Application site pruritus	11.1% 2/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
General disorders Application site erythema	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
General disorders Application site exfoliation	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
General disorders Application site paraesthesia	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	20.0% 1/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
General disorders Chest pain	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Nervous system disorders Headache	22.2% 4/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	10.0% 1/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Nervous system disorders Dizziness	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	20.0% 2/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Nervous system disorders Presyncope	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	20.0% 1/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Respiratory, thoracic and mediastinal disorders Paranasal sinus discomfort	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Skin and subcutaneous tissue disorders Alopecia	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Skin and subcutaneous tissue disorders Dermatitis atopic	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	20.0% 1/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Infections and infestations Bronchitis	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Infections and infestations Nasopharyngitis	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Ear and labyrinth disorders Ear pain	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Eye disorders Abnormal sensation in eye	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	20.0% 1/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Musculoskeletal and connective tissue disorders Limb discomfort	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Renal and urinary disorders Urinary hesitation	5.6% 1/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Nervous system disorders Lethargy	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	20.0% 2/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Nervous system disorders Sensory disturbance	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	10.0% 1/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Gastrointestinal disorders Nausea	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	10.0% 1/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
General disorders Asthenia	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	10.0% 1/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Psychiatric disorders Anxiety	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	10.0% 1/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	10.0% 1/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	10.0% 1/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Vascular disorders Thrombophlebitis	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	10.0% 1/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
General disorders Application site iiritation	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	16.7% 1/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
General disorders Application site dryness	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	16.7% 1/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
General disorders Catheter site inflammation	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	16.7% 1/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Gastrointestinal disorders Flatulence	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	16.7% 1/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Gastrointestinal disorders Gastrointestinal sounds abnormal	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	16.7% 1/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.
Musculoskeletal and connective tissue disorders Pain in extrmity	0.00% 0/18 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/5 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	0.00% 0/10 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.	16.7% 1/6 • AEs were collected up to end of the follow-up. The end of the follow-up duration for the study 202093 was Day 28, for the study AC4112008 was Day 50 and for the study LHH117157 Day 18. Safety population of study number 202093, LHH117157 (Cohort B) and AC4112008 were used to report SAEs and nSAEs.

Additional Information

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• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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