Trial Outcomes & Findings for ESSENCE Study: Efficacy and Safety of SD-101 Cream in Participants With Epidermolysis Bullosa (NCT NCT02384460)

Last Updated: 2020-04-09

Results Overview

Target wounds were monitored at each study visit for complete closure, defined as skin re-epithelialization without drainage. Time to target wound closure was measured from the date of the first administration of the study drug to the date of target wound closure. Participants were censored if they did not have a response within 3 months, or withdrew earlier before the confirmation of their target wound closing. This primary end point displays the mean time to complete target wound closure, analyzed using a Kaplan-Meier approach.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

169 participants

Primary outcome timeframe

From baseline to Month 3 visit

Results posted on

2020-04-09

Participant Flow

Of 210 participants screened for this study, 169 participants were randomly assigned, on a 1:1 basis, to treatment with SD-101-6.0 or placebo at 31 study centers in 13 countries. The first participant was enrolled on 11 March 2015 and the last participant completed the study on 05 July 2017.

Participants had to be \>1 month of age with a diagnosis of simplex, recessive dystrophic, or junctional non-Herlitz Epidermolysis Bullosa (EB) and a target wound with a surface area of 10 to 50 cm\^2 and ≥21 days old to be considered for participation. Participants who did not meet all inclusion/exclusion criteria were eligible for rescreening.

Participant milestones

Participant milestones
Measure	SD-101-6.0 Cream Participants applied SD-101-6.0 cream topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream Participants applied Placebo (SD-101-0.0) cream topically, once a day to the entire body for a period of 90 days.
Overall Study STARTED	82	87
Overall Study Received at Least 1 Dose of Study Drug	82	87
Overall Study COMPLETED	75	80
Overall Study NOT COMPLETED	7	7

Reasons for withdrawal

Reasons for withdrawal
Measure	SD-101-6.0 Cream Participants applied SD-101-6.0 cream topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream Participants applied Placebo (SD-101-0.0) cream topically, once a day to the entire body for a period of 90 days.
Overall Study Protocol Violation	0	1
Overall Study Returned to previous therapeutic regimen	0	1
Overall Study Adverse Event	5	2
Overall Study Withdrawal by Subject	0	3
Overall Study Elective medical treatment	1	0
Overall Study Non-compliance	1	0

Baseline Characteristics

ESSENCE Study: Efficacy and Safety of SD-101 Cream in Participants With Epidermolysis Bullosa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SD-101-6.0 Cream n=82 Participants SD-101-6.0 cream applied topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream n=87 Participants Placebo (SD-101-0.0) cream applied topically, once a day to the entire body for a period of 90 days.	Total n=169 Participants Total of all reporting groups
Age, Continuous	13.8 years STANDARD_DEVIATION 13.15 • n=5 Participants	13.9 years STANDARD_DEVIATION 13.12 • n=7 Participants	13.9 years STANDARD_DEVIATION 13.09 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	48 Participants n=7 Participants	81 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	39 Participants n=7 Participants	88 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	69 Participants n=5 Participants	72 Participants n=7 Participants	141 Participants n=5 Participants
Race/Ethnicity, Customized Black/African American	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
EB type Simplex	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
EB type Recessive dystrophic	57 Participants n=5 Participants	62 Participants n=7 Participants	119 Participants n=5 Participants
EB type Junctional non-Herlitz	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to Month 3 visit

Population: ITT population with post-baseline wound closure data and whose target wound had closed within 3 months.

Outcome measures

Outcome measures
Measure	SD-101-6.0 Cream n=39 Participants Participants applied SD-101-6.0 cream topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream n=45 Participants Participants applied Placebo (SD-101-0.0) cream topically, once a day to the entire body for a period of 90 days.
Time To Complete Target Wound Closure Within 3 Months	41.6 days Standard Deviation 25.50	53.6 days Standard Deviation 28.59

PRIMARY outcome

Timeframe: From baseline to Month 3 visit

Population: ITT population with post-baseline wound closure data and whose target wound had closed within 3 months.

Target wounds were monitored at each study visit for complete closure, defined as skin re-epithelialization without drainage. Participants were considered responders if they experienced complete wound closure at the Week 2 or Months 1, 2, or 3 visits. If a target wound was documented to have closed at a given visit, it was considered closed at all subsequent visits. This primary end point displays the percentage of participants from the ITT population who had complete target wound closure by the end of the study period (that is, 3 months). Analysis was performed on participants with post-baseline wound closure data.

Outcome measures

Outcome measures
Measure	SD-101-6.0 Cream n=79 Participants Participants applied SD-101-6.0 cream topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream n=84 Participants Participants applied Placebo (SD-101-0.0) cream topically, once a day to the entire body for a period of 90 days.
The Percentage Of Participants Experiencing Complete Closure Of Their Target Wound Within 3 Months	49.4 percentage of participants	53.6 percentage of participants

SECONDARY outcome

Timeframe: From baseline to Month 1 and Month 2 visits

Population: Analysis was performed on participants from the ITT population with post-baseline wound closure data.

Target wounds were monitored at each study visit for complete closure, defined as skin re-epithelialization without drainage. The percentage of participants who completed target wound closure at the Month 1 and Month 2 study visits is displayed. If a target wound was documented to have closed at a given visit, it was considered closed at all subsequent visits.

Outcome measures

Outcome measures
Measure	SD-101-6.0 Cream n=79 Participants Participants applied SD-101-6.0 cream topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream n=84 Participants Participants applied Placebo (SD-101-0.0) cream topically, once a day to the entire body for a period of 90 days.
Percentage Of Participants Experiencing Complete Closure Of Their Target Wound At Month 1 And Month 2 Visits Month 1	31.6 percentage of participants	22.6 percentage of participants
Percentage Of Participants Experiencing Complete Closure Of Their Target Wound At Month 1 And Month 2 Visits Month 2	43.0 percentage of participants	42.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 3 visit

Population: Analysis was performed on the ITT population. The ITT population included all randomized participants.

Lesional skin was defined as areas that contained any of the following: blisters, erosions, ulcerations, scabbing, bullae, or eschars, as well as areas that were weeping, sloughing, oozing, crusted, or denuded. BSAI was calculated as a percentage, ranging from 0% to 100%, of affected body surface area, recorded for each defined body region (that is, head/neck, upper limbs, trunk \[includes groin\], and lower limbs), multiplied by the weighting factor, then summed for all body regions.

Outcome measures

Outcome measures
Measure	SD-101-6.0 Cream n=75 Participants Participants applied SD-101-6.0 cream topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream n=78 Participants Participants applied Placebo (SD-101-0.0) cream topically, once a day to the entire body for a period of 90 days.
Change From Baseline In Body Surface Area Index (BSAI) Of Lesional Skin At Month 3 Visit	-4.637 Percentage change in BSAI Standard Error 1.404	-5.319 Percentage change in BSAI Standard Error 1.354

SECONDARY outcome

Timeframe: Baseline, Month 3 visit

Population: Analysis was performed on the ITT population. The ITT population included all randomized participants.

Total body wound burden was calculated using BSAI. A wound defined as an open area on the skin (that is, epidermal covering disrupted). BSAI was calculated as a percentage, ranging from 0% to 100%, of affected body surface area, recorded for each defined body region (that is, head/neck, upper limbs, lower limbs, trunk \[includes groin\]), and multiplied by the weighting factor, then summed for all body regions.

Outcome measures

Outcome measures
Measure	SD-101-6.0 Cream n=75 Participants Participants applied SD-101-6.0 cream topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream n=79 Participants Participants applied Placebo (SD-101-0.0) cream topically, once a day to the entire body for a period of 90 days.
Change From Baseline In BSAI Of Total Body Wound Burden At Month 3 Visit	-3.050 Percentage change in BSAI Standard Error 0.816	-2.922 Percentage change in BSAI Standard Error 0.813

SECONDARY outcome

Timeframe: Baseline, Day 7

Population: Analysis was performed on the ITT population. The ITT population included all randomized participants.

Itching was assessed using the 5-point Itch Man Pruritus Assessment Tool. For participants up to 5 years of age, itching was assessed using caretaker's response and participants 6 years of age and older self-reported their itching assessments based on the following scores: 0=Comfortable, no itch; 1=itches a little, does not interfere with activity; 2=itches more, sometimes interferes with activity; 3=itches a lot, difficult to be still, concentrate; 4=itches most terribly, impossible to sit still or concentrate. Itching scores were categorized into 3 groups based on improvement; Improved or No Itching, Not Improved, and Missing. An itching score reduction from baseline greater than or equal to 1 point on the scale was classed as improved.

Outcome measures

Outcome measures
Measure	SD-101-6.0 Cream n=77 Participants Participants applied SD-101-6.0 cream topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream n=79 Participants Participants applied Placebo (SD-101-0.0) cream topically, once a day to the entire body for a period of 90 days.
Change From Baseline In Itching Score At Day 7	-0.5 units on a scale Standard Deviation 1.31	-0.3 units on a scale Standard Deviation 1.24

SECONDARY outcome

Timeframe: Baseline, Day 7

Population: Analysis was performed on the ITT population. The ITT population included all randomized participants.

Change in pain assessed at Day 7 compared to baseline was measured using the Face, Legs, Activity, Cry, and Consolability (FLACC) behavioral scale for participants 1 month to 3 years of age. Each of the 5 FLACC categories was scored from 0 to 2, which resulted in a total score between 0 and 10 with 0=Relaxed and comfortable, 1 to 3=Mild discomfort, 4 to 6=Moderate pain, and 7 to 10=Severe discomfort/pain. For participants 4 years of age and older, the "Wong Faces Pain Scale" was used. This scale shows a series of faces ranging from a happy face at 0, which represents "no hurt," to a crying face at 10, which represents "hurts worst". Pain scores were categorized into 3 groups based on improvement: Improved or No Pain, Not Improved, and Missing. A pain score reduction from baseline greater than or equal to 2 points on the scale was classed as improved.

Outcome measures

Outcome measures
Measure	SD-101-6.0 Cream n=77 Participants Participants applied SD-101-6.0 cream topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream n=80 Participants Participants applied Placebo (SD-101-0.0) cream topically, once a day to the entire body for a period of 90 days.
Change From Baseline In Pain Score At Day 7	-0.3 units on a scale Standard Deviation 2.57	-0.6 units on a scale Standard Deviation 3.07

Adverse Events

SD-101-6.0 Cream

Serious events: 4 serious events

Other events: 49 other events

Deaths: 0 deaths

Placebo (SD-101-0.0) Cream

Serious events: 8 serious events

Other events: 46 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Patient Advocacy

Amicus Therapeutics, Inc.

Phone: +1-609-662-2000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	SD-101-6.0 Cream n=82 participants at risk SD-101-6.0 cream applied topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream n=87 participants at risk Placebo (SD-101-0.0) cream applied topically, once a day to the entire body for a period of 90 days.
Blood and lymphatic system disorders Anemia	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Cardiac disorders Cardiopulmonary failure	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Gastrointestinal disorders Dysphagia	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Gastrointestinal disorders Oesophageal stenosis	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
General disorders Pyrexia	2.4% 2/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	0.00% 0/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Cystitis	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Gastroenteritis	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Influenza	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	2.3% 2/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Staphylococcal skin infection	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Injury, poisoning and procedural complications Wound	1.2% 1/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	0.00% 0/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Psychiatric disorders Aggression	1.2% 1/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	0.00% 0/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Vascular disorders Circulatory collapse	0.00% 0/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.

Measure	SD-101-6.0 Cream n=82 participants at risk SD-101-6.0 cream applied topically, once a day to the entire body for a period of 90 days.	Placebo (SD-101-0.0) Cream n=87 participants at risk Placebo (SD-101-0.0) cream applied topically, once a day to the entire body for a period of 90 days.
Blood and lymphatic system disorders Anemia	3.7% 3/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	2.3% 2/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Gastrointestinal disorders Vomiting	2.4% 2/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	2.3% 2/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
General disorders Pain	1.2% 1/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	4.6% 4/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
General disorders Pyrexia	6.1% 5/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	10.3% 9/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Ear infection	1.2% 1/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	4.6% 4/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Nasopharyngitis	13.4% 11/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	3.4% 3/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Pharyngitis	1.2% 1/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	4.6% 4/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Skin bacterial infection	1.2% 1/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	4.6% 4/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Skin infection	3.7% 3/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	10.3% 9/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Staphyloccocal skin infection	1.2% 1/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	6.9% 6/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Upper respiratory tract infection	4.9% 4/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	10.3% 9/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Wound infection	7.3% 6/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	5.7% 5/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Infections and infestations Wound infection staphylococcal	1.2% 1/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	4.6% 4/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Injury, poisoning and procedural complications Fall	3.7% 3/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	1.1% 1/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Injury, poisoning and procedural complications Wound	2.4% 2/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	3.4% 3/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	2.4% 2/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	2.3% 2/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Respiratory, thoracic and mediastinal disorders Cough	4.9% 4/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	4.6% 4/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.4% 2/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	4.6% 4/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Skin and subcutaneous tissue disorders Blister	3.7% 3/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	2.3% 2/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Skin and subcutaneous tissue disorders Pruritus	11.0% 9/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	9.2% 8/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.
Skin and subcutaneous tissue disorders Rash	2.4% 2/82 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.	3.4% 3/87 • From baseline up to 3 months. Adverse events (AEs) were defined as treatment-emergent AEs if the AE occurred on or after the first date of application of study drug.