Trial Outcomes & Findings for Study to Assess the Safety of Dupilumab (REGN668/SAR231893) Administered Concomitantly With Topical Corticosteroids (TCS) in Patients With Moderate-to-severe Atopic Dermatitis (AD) (NCT NCT01639040)

Last Updated: 2017-10-13

Results Overview

Any untoward medical occurrence in a subject who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (from start of administration of first dose of study drug to the end of study \[up to Day 78\]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Baseline up to the end of study (up to Day 78)

Results posted on

2017-10-13

Participant Flow

A total of 38 participants were screened in the study between 30 July 2012 and 20 December 2012.

Out of 38 participants, 31 were randomized and treated in the study. Participants were randomized in 2:1 ratio to receive Dupilumab 300 mg or Placebo.

Participant milestones

Participant milestones
Measure	Placebo QW Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days.	Dupilumab 300 mg QW Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days
Overall Study STARTED	10	21
Overall Study COMPLETED	9	21
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo QW Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days.	Dupilumab 300 mg QW Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days
Overall Study Adverse Event	1	0

Baseline Characteristics

Study to Assess the Safety of Dupilumab (REGN668/SAR231893) Administered Concomitantly With Topical Corticosteroids (TCS) in Patients With Moderate-to-severe Atopic Dermatitis (AD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=10 Participants Placebo (for REGN668) once weekly for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days.	REGN668 300 mg n=21 Participants REGN668 300 mg once weekly for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days	Total n=31 Participants Total of all reporting groups
Age, Continuous	37.8 years STANDARD_DEVIATION 16.73 • n=5 Participants	36.0 years STANDARD_DEVIATION 11.26 • n=7 Participants	36.6 years STANDARD_DEVIATION 13.01 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	13 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Eczema Area and Severity Index (EASI) Score	24.1 units on a scale STANDARD_DEVIATION 12.70 • n=5 Participants	23.1 units on a scale STANDARD_DEVIATION 12.35 • n=7 Participants	23.4 units on a scale STANDARD_DEVIATION 12.26 • n=5 Participants
Investigator's Global Assessment (IGA) Score	3.4 units on a scale STANDARD_DEVIATION 0.47 • n=5 Participants	3.4 units on a scale STANDARD_DEVIATION 0.60 • n=7 Participants	3.4 units on a scale STANDARD_DEVIATION 0.55 • n=5 Participants
Pruritus Numerical Rating Scale (NRS) score	5.0 units on a scale STANDARD_DEVIATION 1.39 • n=5 Participants	6.4 units on a scale STANDARD_DEVIATION 2.00 • n=7 Participants	6.0 units on a scale STANDARD_DEVIATION 1.93 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to the end of study (up to Day 78)

Population: Safety population included all randomized participants who received any study drug; based on the treatment received (as treated).

Outcome measures

Outcome measures
Measure	Placebo QW n=10 Participants Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days	Dupilumab 300 mg QW n=21 Participants Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) With at least one TEAE	70.0 percentage of participants	57.1 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) With study drug related TEAEs	40.0 percentage of participants	28.6 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) With serious TEAEs	10.0 percentage of participants	0 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) With TEAEs resulting in study discontinuation	10.0 percentage of participants	0 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 29

Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline assessment; it was based on the treatment allocated (as randomized).

The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. The efficacy data were set to missing after prohibited medication was used or after the participant was discontinued from the study. Then, all missing values were imputed by simple LOCF.

Outcome measures

Outcome measures
Measure	Placebo QW n=10 Participants Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days	Dupilumab 300 mg QW n=21 Participants Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days
Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Score: Reduction of ≥50 at Day 29 - Censored Last Observation Carried Forward (LOCF)	50.0 percentage of participants Interval 18.7 to 81.3	100.0 percentage of participants Interval 83.9 to 100.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 29

Population: FAS included all randomized participants who received at least 1 dose of study medication and had at least 1 post-baseline assessment; it was based on the treatment allocated (as randomized).

Pruritus NRS was an assessment tool that was used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]).

Outcome measures

Outcome measures
Measure	Placebo QW n=10 Participants Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days	Dupilumab 300 mg QW n=21 Participants Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days
Percent Change in Pruritus Numerical Rating Scale (NRS) From Day 1 (Baseline) to Day 29 (Week 4)	-24.7 percent change Standard Deviation 47.30	-70.7 percent change Standard Deviation 21.45

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 29

Outcome measures

Outcome measures
Measure	Placebo QW n=10 Participants Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days	Dupilumab 300 mg QW n=21 Participants Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days
Percentage of Participants Achieving an Investigator's Global Assessment (IGA) Score of "0" or "1" at Day 29	30.0 percentage of participants Interval 6.7 to 65.2	52.4 percentage of participants Interval 29.8 to 74.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 29

IGA was an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). The efficacy data were set to missing after prohibited medication was used or after the participant was discontinued from the study. Then, all missing values were imputed by simple LOCF.

Outcome measures

Outcome measures
Measure	Placebo QW n=10 Participants Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days	Dupilumab 300 mg QW n=21 Participants Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days
Percent Change in Investigator's Global Assessment (IGA) Score From Day 1 (Baseline) to Day 29 (Week 4) - Censored LOCF	-30.6 percent change Standard Deviation 39.00	-52.5 percent change Standard Deviation 21.44

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 29

EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. The efficacy data were set to missing after prohibited medication was used or after the participant was discontinued from the study. Then, all missing values were imputed by simple LOCF.

Outcome measures

Outcome measures
Measure	Placebo QW n=10 Participants Placebo (for Dupilumab) once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent topical corticosteroid (TCS) for up to 28 days	Dupilumab 300 mg QW n=21 Participants Dupilumab 300 mg once weekly (QW) for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days
Percent Change in Eczema Area and Severity Index (EASI) Score From Day 1 (Baseline) to Day 29 (Week 4) - Censored LOCF	-52.5 percent Change Standard Deviation 39.53	-75.6 percent Change Standard Deviation 13.29

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

REGN668 300 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=10 participants at risk Placebo (for REGN668) once weekly for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days	REGN668 300 mg n=21 participants at risk REGN668 300 mg once weekly for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days.
Nervous system disorders Loss of consciousness	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	0.00% 0/21 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).

Other adverse events

Additional Information

Clinical Trial Management

Regeneron Pharmaceuticals, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Not less than 45 days prior to submission for publication or presentation, the Institution shall, or cause the Principal Investigator to, provide the Sponsor with a copy of the Manuscript. The Institution shall consider in good faith any comments from the Sponsor regarding the content, and shall delete Confidential Information upon written request of the Sponsor. At the Sponsor's request, the Institution shall delay publication for an additional 60 days to allow patent applications to be filed.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=10 participants at risk Placebo (for REGN668) once weekly for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days	REGN668 300 mg n=21 participants at risk REGN668 300 mg once weekly for 4 weeks by subcutaneous injection with the background therapy of potent TCS for up to 28 days.
General disorders Injection site erythema	10.0% 1/10 • Number of events 4 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	0.00% 0/21 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Infections and infestations Erysipelas	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	0.00% 0/21 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Infections and infestations Gastroenteritis	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	0.00% 0/21 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Infections and infestations Gastrointestinal infection	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	0.00% 0/21 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Infections and infestations Influenza	0.00% 0/10 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	9.5% 2/21 • Number of events 2 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Infections and infestations Nasopharyngitis	20.0% 2/10 • Number of events 2 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	23.8% 5/21 • Number of events 6 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Infections and infestations Rhinitis	0.00% 0/10 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	9.5% 2/21 • Number of events 3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Infections and infestations Sinusitis	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	4.8% 1/21 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Infections and infestations Vulvovaginal mycotic infection	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	0.00% 0/21 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Investigations Blood pressure increased	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	0.00% 0/21 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Metabolism and nutrition disorders Hyperlipidaemia	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	0.00% 0/21 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Nervous system disorders Headache	10.0% 1/10 • Number of events 6 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	14.3% 3/21 • Number of events 8 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Nervous system disorders Loss of consciousness	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	0.00% 0/21 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Nervous system disorders Somnolence	0.00% 0/10 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	9.5% 2/21 • Number of events 2 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Psychiatric disorders Alcoholism	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	0.00% 0/21 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/10 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	9.5% 2/21 • Number of events 2 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.0% 1/10 • Number of events 1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).	14.3% 3/21 • Number of events 4 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 78) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (day from first dose of study drug to the end of study visit \[up to Day 78\]).