JADE Compare: Study Evaluating Efficacy and Safety of PF-04965842 and Dupilumab in Adult Subjects With Moderate to Severe Atopic Dermatitis on Background Topical Therapy
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT03720470
Collaborator
(none)
838
216
5
16.2
3.9
0.2
Study Details
Study Description
Brief Summary
B7451029 is a Phase 3 study to investigate PF-04965842 in adult patients who have moderate to severe atopic dermatitis and use background topical therapy. The efficacy of two dosage strengths of PF-04965842, 100 mg and 200 mg taken orally once daily will be evaluated relative to placebo over 12 weeks. The efficacy of the two dosage strengths of PF-04965842 will be compared with dupilumab in terms of pruritus relief at 2 weeks. The two dosage strengths of PF-04965842 and dupilumab 300 mg injected subcutaneously once every two weeks (with a loading dose of 600 mg injected on the first day) will also be evaluated relative to placebo over 16 weeks. The safety of the investigational products will be evaluated over the duration of the study. Subjects will use non-medicated emollient at least twice a day and medicated topical therapy such as corticosteroids, calcineurin inhibitors or PDE4 inhibitors, as per protocol guidance, to treat active lesions during the study. Subjects who are randomized to receive one of the two dosage strengths of PF-04965842 will also receive placebo injectable study drug every two weeks until Week 16 and then will continue on receiving only the oral study drug for 4 weeks. Subjects who are randomized to receive dupilumab injections every two weeks will also receive oral placebo to be taken once daily until Week 16 and will then continue to receive only the oral placebo for 4 weeks. Subjects who are randomized to the placebo arms, will receive both daily oral placebo and injectable placebo every two weeks until Week 16, after which they will receive either 100 mg or 200 mg of PF-04965842 taken orally once daily for 4 weeks, dependent upon which arm they have been allocated to. Eligible subjects will have an option to enter a long-term extension study after completing 20 weeks of treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
838 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A PHASE 3 RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY AND SAFETY OF PF-04965842 AND DUPILUMAB IN COMPARISON WITH PLACEBO IN ADULT SUBJECTS ON BACKGROUND TOPICAL THERAPY, WITH MODERATE TO SEVERE ATOPIC DERMATITIS
Actual Study Start Date
:
Oct 29, 2018
Actual Primary Completion Date
:
Dec 27, 2019
Actual Study Completion Date
:
Mar 6, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PF-04965842 100 mg + Placebo Inj followed by PF-04965842 100mg Once-daily oral PF-04965842 100 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 100 mg from Week 16 to Week 20 |
Drug: PF-04965842 100 mg
PF-04965842 100 mg, administered as two tablets to be taken orally once daily as follows:
In the arm "PF-04965842 100 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 100 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20;
In the arm "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" subjects take PF-04965842 100 mg from Week 16 to Week 20.
Drug: Injectable Placebo
Two subcutaneous injections of Placebo (for Dupilumab) administered as a loading dose on Day 1 followed by one injection every other week (q2w) until Week 16.
|
| Experimental: PF-04965842 200 mg + Placebo Inj followed by PF-04965842 200mg Once-daily oral PF-04965842 200 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 200 mg from Week 16 to Week 20 |
Drug: PF-04965842 200 mg
PF-04965842 200 mg, administered as two tablets to be taken orally once daily as follows:
In the arm "PF-04965842 200 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 200 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20;
In the arm "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842" subjects take PF-04965842 200 mg from Week 16 to Week 20.
Drug: Injectable Placebo
Two subcutaneous injections of Placebo (for Dupilumab) administered as a loading dose on Day 1 followed by one injection every other week (q2w) until Week 16.
|
| Active Comparator: Dupilumab Injection + Oral Placebo followed by Oral Placebo Dupilumab injected subcutaneously once every 2 weeks + once-daily oral Placebo from Day 1 until Week 16 followed by once-daily oral Placebo from Week 16 to Week 20 |
Drug: Dupilumab
Two subcutaneous injections of Dupilumab 300 mg as a loading dose administered on Day 1 (for a total of 600 mg) followed by one injection once every two weeks (q2w) until Week 16.
Drug: Oral Placebo
Oral placebo (for PF-04965842) administered as two tablets to be taken orally once daily as follows:
In the arm "Dupilumab Injection + Oral Placebo followed by Oral Placebo," the Oral Placebo is taken together with Dupilumab from Day 1 until Week 16, then by itself to Week 20;
In the arms "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" and "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842," subjects, take Oral Placebo from Day 1 until Week 16.
|
| Placebo Comparator: Oral Placebo + Placebo Inj followed by 100 mg PF-04965842 Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 100 mg PF-04965842 from Week 16 to Week 20 |
Drug: PF-04965842 100 mg
PF-04965842 100 mg, administered as two tablets to be taken orally once daily as follows:
In the arm "PF-04965842 100 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 100 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20;
In the arm "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" subjects take PF-04965842 100 mg from Week 16 to Week 20.
Drug: Oral Placebo
Oral placebo (for PF-04965842) administered as two tablets to be taken orally once daily as follows:
In the arm "Dupilumab Injection + Oral Placebo followed by Oral Placebo," the Oral Placebo is taken together with Dupilumab from Day 1 until Week 16, then by itself to Week 20;
In the arms "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" and "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842," subjects, take Oral Placebo from Day 1 until Week 16.
Drug: Injectable Placebo
Two subcutaneous injections of Placebo (for Dupilumab) administered as a loading dose on Day 1 followed by one injection every other week (q2w) until Week 16.
|
| Placebo Comparator: Oral Placebo + Placebo Inj followed by 200 mg PF-04965842 Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 200 mg PF-04965842 from Week 16 to Week 20 |
Drug: PF-04965842 200 mg
PF-04965842 200 mg, administered as two tablets to be taken orally once daily as follows:
In the arm "PF-04965842 200 mg + Injectable Placebo followed by PF-04965842 100 mg," PF-04965842 200 mg is taken together with Injectable Placebo from Day 1 until Week 16, then by itself from Week 16 to Week 20;
In the arm "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842" subjects take PF-04965842 200 mg from Week 16 to Week 20.
Drug: Oral Placebo
Oral placebo (for PF-04965842) administered as two tablets to be taken orally once daily as follows:
In the arm "Dupilumab Injection + Oral Placebo followed by Oral Placebo," the Oral Placebo is taken together with Dupilumab from Day 1 until Week 16, then by itself to Week 20;
In the arms "Oral Placebo + Injectable Placebo followed by 100 mg PF-04965842" and "Oral Placebo + Injectable Placebo followed by 200 mg PF-04965842," subjects, take Oral Placebo from Day 1 until Week 16.
Drug: Injectable Placebo
Two subcutaneous injections of Placebo (for Dupilumab) administered as a loading dose on Day 1 followed by one injection every other week (q2w) until Week 16.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and a Reduction of Greater Than or Equal to (>=) 2 Points From Baseline at Week 12 [Baseline (the last measurement prior to first dosing on Day 1), Week 12]
IGA assessed severity of atopic dermatitis (AD) on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded scalp, palms and sole.
- Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=75 Percent (%) Improvement From Baseline at Week 12 [Baseline, Week 12]
EASI evaluates severity of participants with AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
Secondary Outcome Measures
- Percentage of Participants With at Least 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Day 2-15, Week 2, 4, 8, 12 and 16 [Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 2, 4, 8, 12, 16]
Participants were asked to assess their worst pruritus/itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst possible itching), where higher scores indicated greater severity.
- Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and a Reduction of >=2 Points From Baseline at Week 2, 4, 8 and 16 [Baseline, Week 2, 4, 8 and 16]
IGA assessed severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded sole, palms and scalp.
- Percentage of Participants Achieving EASI Response >=75% Improvement From Baseline at Week 2, 4, 8 and 16 [Baseline, Week 2, 4, 8 and 16]
EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
- Percentage of Participants Achieving EASI Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16 [Baseline, Week 2, 4, 8, 12 and 16]
EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
- Percentage of Participants Achieving EASI Response >=90% Improvement From Baseline at Week 2, 4, 8, 12 and 16 [Baseline, Week 2, 4, 8,12 and 16]
EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
- Percentage of Participants Achieving EASI Response =100% Improvement From Baseline at Week 2, 4, 8, 12 and 16 [Baseline, Week 2, 4, 8, 12 and 16]
EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
- Time From Baseline to First Achieve at Least 4 Points Improvement in the Severity of Pruritus NRS [Baseline up to Week 16]
Participants were asked to assess their worst pruritus/itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst possible itching), where higher scores indicated greater severity.
- Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8, 12 and 16 [Baseline, Week 2, 4, 8, 12 and 16]
4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in the affected area of a body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Percent BSA for a body region was calculated as = total number of handprints in a body region * % surface area equivalent to 1 handprint. Overall % BSA for an individual: arithmetic mean of % BSA of all 4 body regions, ranges from 0 to 100%, with higher values representing greater severity of AD.
- Percentage BSA at Week 18 and 20 [Week 18 and 20]
4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in the affected area of a body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Percent BSA for a body region was calculated as = total number of handprints in a body region * % surface area equivalent to 1 handprint. Overall % BSA for an individual: arithmetic mean of % BSA of all 4 body regions, ranges from 0 to 100%, with higher values representing greater severity of AD.
- Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8, 12 and 16 [Baseline, Week 2, 4, 8, 12 and 16]
Participant responded to the following question: "Overall, how would you describe your Atopic Dermatitis right now?" on a scale: 0= clear; 1= almost clear; 2= mild; 3= moderate; and 4= severe. Higher scores indicated more severity.
- Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 12 and 16 [Baseline, Week 2, 12 and 16]
DLQI is a 10-item questionnaire that measures the impact of skin disease. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants.
- DLQI at Week 20 [Week 20]
DLQI is a 10-item questionnaire that measures the impact of skin disease. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants.
- Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Index Value at Week 12 and 16 [Baseline, Week 12 and 16]
EQ-5D-5L: standardized participant completed questionnaire consisted of 2 components: a health state profile and an optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. US value sets (with all possible health states) was used for adults in the study, range from 1 to -0.109. Higher (positive) scores = better health state.
- Change From Baseline in EQ-5D-5L Visual Analogue Scale (VAS) Score at Week 12 and 16 [Baseline, Week 12 and 16]
EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state.
- EQ-5D-5L- Index Value at Week 20 [Week 20]
EQ-5D-5L: standardized participant completed questionnaire consisted of 2 components: a health state profile and an optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. US value sets (with all possible health states) was used for adults in the study, range from 1 to -0.109. Higher (positive) scores = better health state.
- EQ-5D-5L- VAS Score at Week 20 [Week 20]
EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state.
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety Scale at Week 12 and 16 [Baseline, Weeks 12 and 16]
HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-Anxiety (HADS-A) scale and HADS-Depression (HADS-D) scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety.
- Change From Baseline in HADS - Depression Scale at Week 12 and 16 [Baseline, Week 12 and 16]
HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-D: sum of all 7 items resulted in score range of 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicating greater severity of depression symptoms.
- HADS - Anxiety Scale at Week 20 [Week 20]
HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety.
- HADS - Depression Scale at Week 20 [Week 20]
HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-D: sum of all 7 items resulted in score range of 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicating greater severity of depression symptoms.
- Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 12 and 16 [Baseline, Week 12 and 16]
POEM is a 7-item participant reported outcome (PRO) measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item is scored as following: "no days (0)", "1-2 days (1)", "3-4 days (2)", "5-6 days (3)" and "every day (4)". The score ranges from 0 to 28, where higher score indicated greater severity.
- POEM at Week 20 [Week 20]
POEM is a 7-item participant reported outcome (PRO) measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item is scored as following: "no days (0)", "1-2 days (1)", "3-4 days (2)", "5-6 days (3)" and "every day (4)". The score ranges from 0 to 28, where higher score indicated greater severity.
- Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score Week 1 to Week 16 [Baseline, Week 1 to Week 16]
PSAAD is a daily participant reported symptom electronic diary. Participants rated their symptoms of AD over the past 24 hours, using 11 items (itchy skin, painful skin, dry skin, flaky skin, cracked skin, bumpy skin, red skin, discolored skin [lighter or darker], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Participant had to think about all the areas of their body affected by their skin condition and chose the number that best described their experience for each of the 11 items, from 0 (no symptoms) to 10 (extreme symptoms), higher scores signified worse skin condition. Total PSAAD score = arithmetic mean of 11 items, 0 (no symptoms) to 10 (extreme symptoms), where higher score = worse skin condition.
- PSAAD Total Score at Week 18 and 20 [Week 18 and 20]
PSAAD is a daily participant reported symptom electronic diary. Participants rated their symptoms of AD over the past 24 hours, using 11 items (itchy skin, painful skin, dry skin, flaky skin, cracked skin, bumpy skin, red skin, discolored skin [lighter or darker], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Participant had to think about all the areas of their body affected by their skin condition and chose the number that best described their experience for each of the 11 items, from 0 (no symptoms) to 10 (extreme symptoms), higher scores signified worse skin condition. Total PSAAD score = arithmetic mean of 11 items, 0 (no symptoms) to 10 (extreme symptoms), where higher score = worse skin condition.
- Percentage of Participants With Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16 [Baseline, Week 2, 4, 8 12 and 16]
SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2,severe=3. The severity scores were summed to give B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale (VAS) where "0" = no itch/no sleeplessness and "10" = the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome.
- Percentage of Participants With SCORAD Response >=75% Improvement From Baseline at Week 2, 4, 8 12 and 16 [Baseline, Week 2, 4, 8 12 and 16]
SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2,severe=3. The severity scores were summed to give B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale (VAS) where "0" = no itch/no sleeplessness and "10" = the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome.
- Change From Baseline in SCORAD Visual Analogue Scale (VAS) of Itch and Sleep Loss at Week 2, 4, 8 12 and 16 [Baseline, Week 2, 4, 8 12 and 16]
SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2,severe=3. The severity scores were summed to give B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale (VAS) where "0" = no itch/no sleeplessness and "10" = the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome.
- SCORAD VAS of Itch and Sleep Loss at Week 18 and 20 [Week 18 and 20]
SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2,severe=3. The severity scores were summed to give B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale (VAS) where "0" = no itch/no sleeplessness and "10" = the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome.
- Least Square Mean of Number of Steroid-free Days From Baseline up to Week 16 [Baseline up to Week 16]
Number of days when a corticosteroid as a concomitant medication was not used up to Week 16 is reported as Least square mean in this outcome measure.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female subjects aged 18 years or older at the time of informed consent
-
Diagnosis of atopic dermatitis (AD) for at least 1 year and current status of moderate to severe disease (>= the following scores: BSA 10%, IGA 3, EASI 16, Pruritus NRS severity 4)
-
Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with medicated topical therapy for AD for at least 4 weeks, or who have required systemic therapies for control of their disease.
-
Must be willing and able to comply with standardized background topical therapy, as per protocol guidelines throughout the study
-
Female subjects who are of childbearing potential must not be intending to become pregnant, currently pregnant, or lactating. The following conditions apply:
-
Female subjects of childbearing potential must have a confirmed negative pregnancy test prior to randomization;
-
Female subjects of childbearing potential must agree to use a highly effective method of contraception for the duration of the active treatment period and for at least 28 days after the last dose of investigational product.
-
Female subjects of non-childbearing potential must meet at least 1 of the following criteria:
-
Have undergone a documented hysterectomy and/or bilateral oophorectomy;
-
Have medically confirmed ovarian failure; or
-
Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state.
All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
-If receiving concomitant medications for any reason other than AD, must be on a stable regimen prior to Day 1 and through the duration of the study
Exclusion Criteria:
-
Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
-
Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, Q wave interval abnormalities, current or history of certain infections, cancer, lymphoproliferative disorders and other medical conditions at the discretion of the investigator
-
Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
-
Other active nonAD inflammatory skin diseases or conditions affecting skin
-
Prior treatment with JAK inhibitors
-
Previous treatment with dupilumab
-
Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Research Center of Alabama, LLC | Birmingham | Alabama | United States | 35209 |
| 2 | The University Of Alabama At Birmingham | Birmingham | Alabama | United States | 35233 |
| 3 | Marvel Research, LLC | Huntington Beach | California | United States | 92647 |
| 4 | Alliance Research Centers | Laguna Hills | California | United States | 92653 |
| 5 | Allergy & Asthma Care Center of Southern California | Long Beach | California | United States | 90808 |
| 6 | Allergy & Asthma Associates of Southern California dba Southern California Research | Mission Viejo | California | United States | 92691 |
| 7 | Dermatology Specialists, Inc. | Murrieta | California | United States | 92562 |
| 8 | MedDerm Associates | San Diego | California | United States | 92103 |
| 9 | Clinical Science Institute | Santa Monica | California | United States | 90404 |
| 10 | Synexus Clinical Research US, Inc. | Santa Rosa | California | United States | 95405 |
| 11 | IMMUNOe Research Centers | Centennial | Colorado | United States | 80112 |
| 12 | Renaissance Research and Medical Group, Inc | Cape Coral | Florida | United States | 33991 |
| 13 | C & R Research Services USA, Inc | Coral Gables | Florida | United States | 33134 |
| 14 | Florida Academic Centers Research and Education, LLC | Coral Gables | Florida | United States | 33134 |
| 15 | Moonshine Research Center, Inc. | Doral | Florida | United States | 33166 |
| 16 | Solutions Through Advanced Research, Inc. | Jacksonville | Florida | United States | 32256 |
| 17 | Olympian Clinical Research | Largo | Florida | United States | 33770 |
| 18 | Wellness Clinical Research, LLC | Miami Lakes | Florida | United States | 33016 |
| 19 | Savin Medical Group LLC | Miami | Florida | United States | 33126 |
| 20 | ForCare Clinical Research | Tampa | Florida | United States | 33613 |
| 21 | Research Institute of Southeast, LLC | West Palm Beach | Florida | United States | 33401 |
| 22 | Research Institute of the Southeast, LLC | West Palm Beach | Florida | United States | 33401 |
| 23 | Columbus Regional Research Institute | Columbus | Georgia | United States | 31904 |
| 24 | Idaho Allergy and Research | Eagle | Idaho | United States | 83616 |
| 25 | ASR, LLC | Nampa | Idaho | United States | 83687 |
| 26 | Great Lakes Clinical Trials | Chicago | Illinois | United States | 60640 |
| 27 | Midwest Allergy Sinus Asthma, SC | Normal | Illinois | United States | 61761 |
| 28 | NorthShore University HealthSystem | Skokie | Illinois | United States | 60077 |
| 29 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
| 30 | Dundee Dermatology | West Dundee | Illinois | United States | 60118 |
| 31 | The Indiana Clinical Trials Center | Plainfield | Indiana | United States | 46168 |
| 32 | Forefront Dermatology, S.C. | Louisville | Kentucky | United States | 40202 |
| 33 | Meridian Clinical Research, LLC | Baton Rouge | Louisiana | United States | 70808 |
| 34 | Clinical Research Institute, Inc. | Minneapolis | Minnesota | United States | 55402 |
| 35 | Skin Laser and Surgery Specialists of NY and NJ | Hackensack | New Jersey | United States | 07601 |
| 36 | Forest Hills Dermatology Group | Kew Gardens | New York | United States | 11374 |
| 37 | Juva Skin and Laser Center | New York | New York | United States | 10022 |
| 38 | TrialSpark, Inc (Russell Cohen) | Oceanside | New York | United States | 11572 |
| 39 | Cary Dermatology Center, PA | Cary | North Carolina | United States | 27511 |
| 40 | PMG Research of Raleigh, LLC d/b/a PMG Research of Cary | Cary | North Carolina | United States | 27518 |
| 41 | Medication Management, LLC | Greensboro | North Carolina | United States | 27408 |
| 42 | PMG Research Inc., d/b/a PMG Research of Piedmont HealthCare | Statesville | North Carolina | United States | 28625 |
| 43 | Winston-Salem Dermatology and Surgery Center, PLLC | Winston-Salem | North Carolina | United States | 27103 |
| 44 | University Hospitals Cleveland Medical Center | Cleveland | Ohio | United States | 44106 |
| 45 | Newton Clinical Research | Oklahoma City | Oklahoma | United States | 73120 |
| 46 | Vital Prospects Clinical Research Institute, P.C. | Tulsa | Oklahoma | United States | 74136 |
| 47 | Portland Clinical Research dba Columbia Allergy & Asthma Clinic | Clackamas | Oregon | United States | 97015 |
| 48 | Crisor, LLC | Medford | Oregon | United States | 97504 |
| 49 | Oregon Health & Science University (OHSU) | Portland | Oregon | United States | 97239 |
| 50 | Paddington Testing Co, Inc. | Philadelphia | Pennsylvania | United States | 19103 |
| 51 | Synexus Clinical Research US, Inc. | Anderson | South Carolina | United States | 29621 |
| 52 | Synexus Clinical Research US. Inc. | Greer | South Carolina | United States | 29651 |
| 53 | Health Concepts | Rapid City | South Dakota | United States | 57702 |
| 54 | Arlington Research Center, Inc. | Arlington | Texas | United States | 76011 |
| 55 | Austin Institute for Clinical Research, Inc. | Austin | Texas | United States | 78705 |
| 56 | Center for Clinical Studies, LTD. LLP | Houston | Texas | United States | 77004 |
| 57 | Center for Clinical Studies, LTD. LLP | Webster | Texas | United States | 77598 |
| 58 | Jordan Valley Dermatology Center | West Jordan | Utah | United States | 84088 |
| 59 | Virginia Dermatology and Skin Cancer Center | Norfolk | Virginia | United States | 23502 |
| 60 | Velocity Urgent Care | Norfolk | Virginia | United States | 23518 |
| 61 | Woden Dermatology | Phillip | Australian Capital Territory | Australia | 2606 |
| 62 | Australian Clinical Research Network | Maroubra | New South Wales | Australia | 2035 |
| 63 | The Skin Centre | Benowa | Queensland | Australia | 4217 |
| 64 | Veracity Clinical Research Pty Ltd | Woolloongabba | Queensland | Australia | 4102 |
| 65 | North Eastern Health Specialists | Hectorville | South Australia | Australia | 5073 |
| 66 | Box Hill Hospital | Box Hill | Victoria | Australia | 3128 |
| 67 | Emeritus Research | Camberwell | Victoria | Australia | 3124 |
| 68 | Skin and Cancer Foundation Inc | Carlton | Victoria | Australia | 3053 |
| 69 | Sinclair Dermatology | East Melbourne | Victoria | Australia | 3002 |
| 70 | Royal Melbourne Hospital | Parkville | Victoria | Australia | 3050 |
| 71 | DCC 2/Sofia EOOD | Sofia | Bulgaria | 1000 | |
| 72 | "DCC Aleksandrovska" EOOD | Sofia | Bulgaria | 1431 | |
| 73 | Dermatology Clinic "Sofia" Ltd | Sofia | Bulgaria | 1756 | |
| 74 | "Mc Synexus Sofia" Eood | Sofia | Bulgaria | 1784 | |
| 75 | Medical Centre Synexus Sofia EOOD-branch Stara Zagora | Stara Zagora | Bulgaria | 6000 | |
| 76 | "DCC "Mladost-M Varna" OOD | Varna | Bulgaria | 9000 | |
| 77 | Pacific Dermaesthetics Inc. | Vancouver | British Columbia | Canada | V6H4E1 |
| 78 | Wiseman Dermatology Research Inc. | Winnipeg | Manitoba | Canada | R3M3Z4 |
| 79 | DermEffects | London | Ontario | Canada | N6H 5L5 |
| 80 | Lynderm Research Inc. | Markham | Ontario | Canada | L3P 1X2 |
| 81 | North Bay Dermatology Centre | North Bay | Ontario | Canada | P1B 3Z7 |
| 82 | SKiN Centre for Dermatology | Peterborough | Ontario | Canada | K9J5K2 |
| 83 | Toronto Research Centre | Toronto | Ontario | Canada | M3H5Y8 |
| 84 | AvantDerm Clinical Research | Toronto | Ontario | Canada | M5A 3R6 |
| 85 | Manna Research (Toronto) | Toronto | Ontario | Canada | M9W 4L6 |
| 86 | Innovaderm Research Inc. | Montréal | Quebec | Canada | H2X 2V1 |
| 87 | Dr. Rachel Asiniwasis Medical Prof Corp | Regina | Saskatchewan | Canada | S4V1R9 |
| 88 | Centro Medico SkinMed Limitada | Santiago | Region Metropolitana | Chile | 7580206 |
| 89 | Clinica Dermacross S.A. | Santiago | Region Metropolitana | Chile | 7640881 |
| 90 | Centro Internacional de Estudios Clinicos - CIEC | Santiago | Region Metropolitana | Chile | 8420383 |
| 91 | MIRES (M y F Estudios ClÃnicos Limitada) | Santiago | Región Metropolitana | Chile | 7750495 |
| 92 | Dermamedica S.R.O. | Nachod | Czechia | 547 01 | |
| 93 | CCR Ostrava, s.r.o. | Ostrava | Czechia | 702 00 | |
| 94 | BENU Lekarna | Pardubice | Czechia | 530 02 | |
| 95 | CCR Czech, a.s. | Pardubice | Czechia | 530 02 | |
| 96 | Nemocnice Pardubickeho kraje a.s., Pardubicka nemocnice, odd Dermatologie | Pardubice | Czechia | 532 03 | |
| 97 | Sanatorium profesora Arenbergera | Praha 1 | Czechia | 11000 | |
| 98 | Lekarna U sv. Ignace | Praha 2 | Czechia | 120 00 | |
| 99 | Synexus Czech, s.r.o. | Praha 2 | Czechia | 120 00 | |
| 100 | CCR Prague, s.r.o. | Praha 3 | Czechia | 130 00 | |
| 101 | Licca Clinical Research Institute | Augsburg | Germany | 86179 | |
| 102 | Fachklinik Bad Bentheim | Bad Bentheim | Germany | 48455 | |
| 103 | Klinikum Bielefeld Rosenhohe | Bielefeld | Germany | 33647 | |
| 104 | Universitätsklinikum Bonn AöR | Bonn | Germany | 53105 | |
| 105 | Klinische Forschung Dresden GmbH | Dresden | Germany | 01069 | |
| 106 | Universitaetsklinikum Carl Gustav Carus der Technischen Universitaet Dresden | Dresden | Germany | 01307 | |
| 107 | IKF Pneumologie GmbH & Co KG, Institut fuer klinische Forschung | Frankfurt | Germany | 60596 | |
| 108 | Universitätsklinikum und Poliklinik für Dermatologie und Venerologie | Halle | Germany | 06120 | |
| 109 | Universitaetsklinikum Schleswig-Holstein, Campus Kiel | Kiel | Germany | 24105 | |
| 110 | Studienzentrum Dr. med. Beate Schwarz | Langenau | Germany | 89129 | |
| 111 | SIBAmed Studienzentrum GmbH & Co KG | Leipzig | Germany | 04103 | |
| 112 | Universitaetsklinikum Schleswig-Holstein/Campus Luebeck | Luebeck | Germany | 23538 | |
| 113 | Dermatologische Gemeinschaftspraxis Dres. Scholz, Sebastian, Schilling | Mahlow | Germany | 15831 | |
| 114 | Universitätsklinikum Marburg | Marburg | Germany | 35043 | |
| 115 | University of Muenster | Muenster | Germany | 48149 | |
| 116 | SE AOK Bor-, Nemikortani es Boronkologiai Klinika | Budapest | Hungary | 1085 | |
| 117 | Debreceni Egyetem Klinikai Kozpont | Debrecen | Hungary | 4032 | |
| 118 | Synexus Magyarország Egészségügyi Szolgáltató Kft. Synexus Gyula DRS | Gyula | Hungary | 5700 | |
| 119 | Trial Pharma Kft. | Püspökladány | Hungary | 4150 | |
| 120 | Medmare Bt | Veszprem | Hungary | 8200 | |
| 121 | Fondazione Policlinico Universitario A. Gemelli IRCCS Universita Cattolica del Sacro Cuore | Roma | RM | Italy | 00168 |
| 122 | AOU Policlinico di Modena, Struttura Complessa di Dermatologia | Modena | Italy | 41124 | |
| 123 | Kawashima Dermatology Clinic | Ichikawa | Chiba | Japan | 272-0033 |
| 124 | Takagi Dermatological Clinic | Obihiro | Hokkaido | Japan | 080-0013 |
| 125 | Dermatology Shimizu Clinic | Kobe | Hyogo | Japan | 657-0846 |
| 126 | Noguchi Dermatology Clinic | Kamimashiki-gun | Kumamoto | Japan | 861-3101 |
| 127 | Osaka Habikino Medical Center | Habikino | Osaka | Japan | 583-8588 |
| 128 | Kume Clinic | Sakai | Osaka | Japan | 593-8324 |
| 129 | Iidabashi Skin Clinic | Chiyoda-ku | Tokyo | Japan | 102-0072 |
| 130 | Fukuwa Clinic | Chuo-ku | Tokyo | Japan | 104-0031 |
| 131 | Tokyo Medical University Hospital | Shinjyuku-ku | Tokyo | Japan | 160-0023 |
| 132 | Hoshikuma Dermatology・Allergy Clinic | Fukuoka | Japan | 814-0171 | |
| 133 | Matsuda Tomoko Dermatological Clinic | Fukuoka | Japan | 819-0167 | |
| 134 | Sanrui Hifuka | Saitama | Japan | 330-0854 | |
| 135 | Korea University Ansan Hospital | Ansan-si | Gyeonggi-do | Korea, Republic of | 15355 |
| 136 | Soon Chun Hyang University Bucheon Hospital | Bucheon-si | Gyeonggi-do | Korea, Republic of | 14584 |
| 137 | Chungnam National University Hospital CNUH | Daejeon | Korea, Republic of | 35015 | |
| 138 | The Catholic University of Korea, Incheon St. Mary's Hospital | Incheon | Korea, Republic of | 21431 | |
| 139 | Severance Hospital, Yonsei Univ. Health System | Seoul | Korea, Republic of | 03722 | |
| 140 | Chung-Ang University Hospital | Seoul | Korea, Republic of | 06973 | |
| 141 | Hallym University Kangnam Sacred Heart Hospital | Seoul | Korea, Republic of | 07441 | |
| 142 | Riga 1st Hospital, Clinic for Dermatology and STD | Riga | Latvia | LV-1001 | |
| 143 | Aesthetic dermatology clinic of Prof. J. Kisis | Riga | Latvia | LV-1003 | |
| 144 | Childrens Clinical University Hospital State SLLC | Riga | Latvia | LV-1004 | |
| 145 | Health and aesthetics Ltd | Riga | Latvia | LV-1009 | |
| 146 | Outpatient Clinic of Ventspils | Ventspils | Latvia | LV-3601 | |
| 147 | Cryptex Investigación ClÃnica, S.A. de C.V. | Cuauhtemoc | Mexico CITY | Mexico | 06100 |
| 148 | Arke Estudios Clinicos S.A. de C.V. | Cuauhtemoc | Mexico CITY | Mexico | 06700 |
| 149 | Eukarya Pharmasite S.C. | Monterrey | Nuevo LEON | Mexico | 64718 |
| 150 | SMIQ. S. de R. L. de C.V. | Queretaro | Mexico | 76070 | |
| 151 | NZOZ Specjalistyczny Osrodek Dermatologiczny "DERMAL" | Bialystok | Poland | 15-453 | |
| 152 | Centrum Medyczne SENSEMED | Chorzow | Poland | 41-500 | |
| 153 | Synexus Polska Sp. z o.o. Oddzial w Czestochowie | Czestochowa | Poland | 42-202 | |
| 154 | COPERNICUS-SZPITAL Oddzial Dermatologii | Gdansk | Poland | 80-152 | |
| 155 | Uniwersyteckie Centrum Kliniczne, Klinika Dermatologii, Wenerologii i Alergologii | Gdansk | Poland | 80-214 | |
| 156 | Synexus Polska Sp. z o.o. Oddzial w Gdyni | Gdynia | Poland | 81-537 | |
| 157 | MCBK | Grodzisk Mazowiecki | Poland | 05-825 | |
| 158 | Synexus Polska Sp. z o.o. Oddzial w Katowicach | Katowice | Poland | 40-040 | |
| 159 | Care Clinic Centrum Medyczne | Katowice | Poland | 40-568 | |
| 160 | Centrum Medyczne Angelius Provita | Katowice | Poland | 40-611 | |
| 161 | Gabinet Dermatologiczny Beata Krecisz | Kielce | Poland | 25-155 | |
| 162 | Centrum Medyczne Plejady | Krakow | Poland | 30-363 | |
| 163 | AWP Klinika Dermatologii Pod Fortem Anna Wojas-Pelc | Krakow | Poland | 31-302 | |
| 164 | Krakowskie Centrum Medyczne Sp. z o.o. | Krakow | Poland | 31-501 | |
| 165 | Centrum Medyczne Promed | Krakow | Poland | 31-513 | |
| 166 | Prywatna Praktyka Lekarska - Adam Smialowski | Ksawerow | Poland | 95-054 | |
| 167 | Dermoklinika-Centrum Medyczne s.c. M. Kierstan, J. Narbutt, A. Lesiak | Lodz | Poland | 90-436 | |
| 168 | Salve Medica Sp. z o.o. Sp. k. | Lodz | Poland | 91-211 | |
| 169 | KO-MED Centra Kliniczne Lublin II | Lublin | Poland | 20-362 | |
| 170 | NZOZ "Med-Laser" Borzecki Spolka Jawna | Lublin | Poland | 20-406 | |
| 171 | Dermedic Jacek Zdybski | Ostrowiec Swietokrzyski | Poland | 27-400 | |
| 172 | Synexus Polska Sp. z o.o. Oddzial w Poznaniu | Poznan | Poland | 60-702 | |
| 173 | Clinical Research Center Spolka z ograniczona odpowiedzialnoscia MEDIC-R Sp.k. | Poznan | Poland | 60-848 | |
| 174 | LIFT-MED Spolka Akcyjna | Rybnik | Poland | 44-200 | |
| 175 | Kliniczny Szpital Wojewodzki nr 1 im. F. Chopina, Klinika Dermatologii | Rzeszow | Poland | 35-055 | |
| 176 | EMED Centrum Uslug Medycznych Ewa Smialek | Rzeszow | Poland | 35-205 | |
| 177 | Twoja Przychodnia - Szczecinskie Centrum Medyczne | Szczecin | Poland | 71-434 | |
| 178 | Medycyna Kliniczna | Warszawa | Poland | 00-874 | |
| 179 | Synexus Polska Sp. z o.o. Oddzial w Warszawie | Warszawa | Poland | 01-192 | |
| 180 | MTZ Clinical Research Sp. z o.o. | Warszawa | Poland | 02-106 | |
| 181 | RCMed Oddzial Warszawa | Warszawa | Poland | 02-657 | |
| 182 | Carpe Diem Centrum Medycyny Estetycznej | Warszawa | Poland | 02-661 | |
| 183 | "REUMATIKA - Centrum Reumatologii" NZOZ | Warszawa | Poland | 02-691 | |
| 184 | Klinika Ambroziak Sp. z o.o. | Warszawa | Poland | 02-758 | |
| 185 | EMC Instytut Medyczny S.A. Przychodnia przy ul. Lowieckiej | Wroclaw | Poland | 50-220 | |
| 186 | Synexus Polska Sp. z o.o. Oddzial we Wroclawiu | Wroclaw | Poland | 50-381 | |
| 187 | Lukasz Matusiak "4Health" | Wroclaw | Poland | 50-566 | |
| 188 | Centrum Medyczne Oporow | Wroclaw | Poland | 52-416 | |
| 189 | SUMMIT CLINICAL RESEARCH, s.r.o. | Bratislava | Slovakia | 831 01 | |
| 190 | Nemocnica Kosice-Saca, a.s., 1. sukromna nemocnica | Kosice-Saca | Slovakia | 040 15 | |
| 191 | Pedi-Derma s.r.o. | Kosice | Slovakia | 04001 | |
| 192 | Fakultna nemocnica s poliklinikou Nove Zamky, Dermatovenerologicka Klinika | Nove Zamky | Slovakia | 940 34 | |
| 193 | SANARE spol. s.r.o., Dermatovenerologicka ambulancia | Svidnik | Slovakia | 089 01 | |
| 194 | Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona | Spain | 08016 |
| 195 | Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona | Spain | 08916 |
| 196 | Hospital Universitario Fundacion Alcorcon | Alcorcon | Madrid | Spain | 28922 |
| 197 | Hospital Universitario Puerta de Hierro de Majadahonda | Majadahonda | Madrid | Spain | 28222 |
| 198 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
| 199 | Hospital Universitario y Politecnico La Fe | Valencia | Spain | 46026 | |
| 200 | Taipei Veterans General Hospital | Taipei | Taiwan (r.o.c) | Taiwan | 11217 |
| 201 | Chung Shan Medical University Hospital (CSMUH) | Taichung City | Taiwan | 40201 | |
| 202 | Taichung Veterans General Hospital | Taichung | Taiwan | 40705 | |
| 203 | National Cheng-Kung University Hospital | Tainan | Taiwan | 704 | |
| 204 | National Taiwan University Hospital | Taipei | Taiwan | 100 | |
| 205 | Mackay Memorial Hospital | Taipei | Taiwan | 10449 | |
| 206 | Medinova Research -West London Dedicated Research Centre | Wokingham | Berkshire | United Kingdom | RG40 1XS |
| 207 | Derriford Hospital | Plymouth | Devon | United Kingdom | PL6 8DH |
| 208 | Medinova Research, East London Dedicated Research Centre | Romford | Essex | United Kingdom | RM1 3PJ |
| 209 | Guy's Hospital-Guy's and St Thomas NHS Foundation Trust | London | Greater London | United Kingdom | SE1 9RT |
| 210 | Medinova Research, South London Clinical Trial Centre | Sidcup | Kent | United Kingdom | DA14 6LT |
| 211 | MeDiNova Research North London Dedicated Research Centre | Northwood | Middlesex | United Kingdom | HA6 2RN |
| 212 | Medinova Research | Yaxley | Peterborough | United Kingdom | PE7 3JL |
| 213 | Medinova Research, Warwickshire Dedicated Research Centre | Kenilworth | Warwickshire | United Kingdom | CV8 1JD |
| 214 | Medinova, Yorkshire Quality Research Site | Shipley | WEST Yorkshire | United Kingdom | BD18 3SA |
| 215 | MeDiNova Northamptonshire Dedicated Research Centre | Corby | United Kingdom | NN18 9EZ | |
| 216 | West Glasgow ACH, NHS Greater Glasgow and Clyde | Glasgow | United Kingdom | G3 8SJ |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03720470
Other Study ID Numbers:
- B7451029
- COMPARE
- 2018-002573-21
First Posted:
Oct 25, 2018
Last Update Posted:
Jan 19, 2021
Last Verified:
Dec 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | The study had treatment period of 20 weeks. The first part of this treatment period consists of a 16-week randomized, double-blind, placebo-controlled, double-dummy treatment period where participants received PF-04965842, dupilumab and placebo. The randomization and double-blind was maintained during the final 4 weeks of the treatment period, but participants only received PF-04965842 and placebo. |
| Arm/Group Title | Placebo up to Week 16 | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 milligram (mg) tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, followed by administration of PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, followed by administration of PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, followed by administration of oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. |
| Period Title: Treatment Period: First Part 16 Weeks | ||||||
| STARTED | 131 | 0 | 0 | 238 | 226 | 243 |
| Treated/ Safety Analysis Set | 131 | 0 | 0 | 238 | 226 | 242 |
| Full Analysis Set | 131 | 0 | 0 | 238 | 226 | 242 |
| COMPLETED | 117 | 0 | 0 | 217 | 208 | 223 |
| NOT COMPLETED | 14 | 0 | 0 | 21 | 18 | 20 |
| Period Title: Treatment Period: First Part 16 Weeks | ||||||
| STARTED | 0 | 60 | 57 | 217 | 208 | 223 |
| Treated/ Safety Analysis Set | 0 | 60 | 57 | 217 | 208 | 223 |
| Full Analysis Set | 0 | 60 | 57 | 217 | 208 | 223 |
| COMPLETED | 0 | 58 | 55 | 210 | 204 | 218 |
| NOT COMPLETED | 0 | 2 | 2 | 7 | 4 | 5 |
Baseline Characteristics
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, followed by administration of PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, followed by administration of PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, followed by administration of oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. | Total of all reporting groups |
| Overall Participants | 131 | 238 | 226 | 242 | 837 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
121
92.4%
|
224
94.1%
|
211
93.4%
|
227
93.8%
|
783
93.5%
|
| >=65 years |
10
7.6%
|
14
5.9%
|
15
6.6%
|
15
6.2%
|
54
6.5%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
54
41.2%
|
118
49.6%
|
122
54%
|
134
55.4%
|
428
51.1%
|
| Male |
77
58.8%
|
120
50.4%
|
104
46%
|
108
44.6%
|
409
48.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
16
12.2%
|
35
14.7%
|
36
15.9%
|
37
15.3%
|
124
14.8%
|
| Not Hispanic or Latino |
113
86.3%
|
200
84%
|
187
82.7%
|
201
83.1%
|
701
83.8%
|
| Unknown or Not Reported |
2
1.5%
|
3
1.3%
|
3
1.3%
|
4
1.7%
|
12
1.4%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
2
1.5%
|
1
0.4%
|
0
0%
|
2
0.8%
|
5
0.6%
|
| Asian |
31
23.7%
|
48
20.2%
|
53
23.5%
|
46
19%
|
178
21.3%
|
| Native Hawaiian or Other Pacific Islander |
1
0.8%
|
0
0%
|
1
0.4%
|
0
0%
|
2
0.2%
|
| Black or African American |
6
4.6%
|
6
2.5%
|
9
4%
|
14
5.8%
|
35
4.2%
|
| White |
87
66.4%
|
182
76.5%
|
161
71.2%
|
176
72.7%
|
606
72.4%
|
| More than one race |
1
0.8%
|
1
0.4%
|
1
0.4%
|
2
0.8%
|
5
0.6%
|
| Unknown or Not Reported |
3
2.3%
|
0
0%
|
1
0.4%
|
2
0.8%
|
6
0.7%
|
Outcome Measures
| Title | Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and a Reduction of Greater Than or Equal to (>=) 2 Points From Baseline at Week 12 |
|---|---|
| Description | IGA assessed severity of atopic dermatitis (AD) on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded scalp, palms and sole. |
| Time Frame | Baseline (the last measurement prior to first dosing on Day 1), Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 129 | 235 | 219 | 241 |
| Number (95% Confidence Interval) [Percentage of participants] |
14.0
10.7%
|
36.6
15.4%
|
48.4
21.4%
|
36.5
15.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, PF-04965842 100 mg + Placebo Injection up to Week 16 |
|---|---|---|
| Comments | Difference in percentage (PF-04965842 versus placebo) and confidence interval (CI) for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | 23.1 | |
| Confidence Interval |
(2-Sided) 95% 14.7 to 31.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, PF-04965842 200 mg + Placebo Injection up to Week 16 |
|---|---|---|
| Comments | Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 34.8 | |
| Confidence Interval |
(2-Sided) 95% 26.1 to 43.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=75 Percent (%) Improvement From Baseline at Week 12 |
|---|---|
| Description | EASI evaluates severity of participants with AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD. |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 129 | 235 | 219 | 241 |
| Number (95% Confidence Interval) [Percentage of participants] |
27.1
20.7%
|
58.7
24.7%
|
70.3
31.1%
|
58.1
24%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, PF-04965842 100 mg + Placebo Injection up to Week 16 |
|---|---|---|
| Comments | Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | 31.9 | |
| Confidence Interval |
(2-Sided) 95% 22.2 to 41.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, PF-04965842 200 mg + Placebo Injection up to Week 16 |
|---|---|---|
| Comments | Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 43.2 | |
| Confidence Interval |
(2-Sided) 95% 33.7 to 52.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With at Least 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Day 2-15, Week 2, 4, 8, 12 and 16 |
|---|---|
| Description | Participants were asked to assess their worst pruritus/itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst possible itching), where higher scores indicated greater severity. |
| Time Frame | Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 2, 4, 8, 12, 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 242 |
| Day 2 |
5.1
3.9%
|
5.9
2.5%
|
7.4
3.3%
|
2.4
1%
|
| Day 3 |
7.9
6%
|
8.4
3.5%
|
14.8
6.5%
|
3.3
1.4%
|
| Day 4 |
6.0
4.6%
|
11.6
4.9%
|
18.6
8.2%
|
5.6
2.3%
|
| Day 5 |
7.6
5.8%
|
14.2
6%
|
26.5
11.7%
|
9.5
3.9%
|
| Day 6 |
10.9
8.3%
|
15.0
6.3%
|
25.1
11.1%
|
14.0
5.8%
|
| Day 7 |
11.1
8.5%
|
20.1
8.4%
|
28.8
12.7%
|
13.4
5.5%
|
| Day 8 |
14.4
11%
|
21.4
9%
|
33.3
14.7%
|
16.5
6.8%
|
| Day 9 |
13.0
9.9%
|
24.0
10.1%
|
34.1
15.1%
|
14.8
6.1%
|
| Day 10 |
13.2
10.1%
|
25.6
10.8%
|
34.3
15.2%
|
17.1
7.1%
|
| Day 11 |
12.7
9.7%
|
25.4
10.7%
|
39.5
17.5%
|
20.5
8.5%
|
| Day 12 |
12.0
9.2%
|
25.5
10.7%
|
44.1
19.5%
|
21.9
9%
|
| Day 13 |
13.2
10.1%
|
30.6
12.9%
|
43.8
19.4%
|
23.6
9.8%
|
| Day 14 |
15.7
12%
|
31.4
13.2%
|
45.7
20.2%
|
24.5
10.1%
|
| Day 15 |
11.1
8.5%
|
30.4
12.8%
|
49.0
21.7%
|
26.5
11%
|
| Week 2 |
13.8
10.5%
|
31.8
13.4%
|
49.1
21.7%
|
26.4
10.9%
|
| Week 4 |
20.2
15.4%
|
44.6
18.7%
|
59.3
26.2%
|
45.3
18.7%
|
| Week 8 |
27.0
20.6%
|
47.5
20%
|
64.0
28.3%
|
50.7
21%
|
| Week 12 |
28.9
22.1%
|
47.5
20%
|
63.1
27.9%
|
54.5
22.5%
|
| Week 16 |
28.7
21.9%
|
47.0
19.7%
|
62.8
27.8%
|
57.1
23.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, PF-04965842 100 mg + Placebo Injection up to Week 16 |
|---|---|---|
| Comments | Week 2: Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | 17.9 | |
| Confidence Interval |
(2-Sided) 95% 9.5 to 26.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, PF-04965842 200 mg + Placebo Injection up to Week 16 |
|---|---|---|
| Comments | Week 2: Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 34.9 | |
| Confidence Interval |
(2-Sided) 95% 26.0 to 43.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PF-04965842 100 mg + Placebo Injection up to Week 16, Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|
| Comments | Week 2: Difference in percentage (PF-04965842 versus dupilumab) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2084 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 5.2 | |
| Confidence Interval |
(2-Sided) 95% -2.9 to 13.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PF-04965842 200 mg + Placebo Injection up to Week 16, Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|
| Comments | Week 2: Difference in percentage (PF-04965842 versus dupilumab) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 22.1 | |
| Confidence Interval |
(2-Sided) 95% 13.5 to 30.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and a Reduction of >=2 Points From Baseline at Week 2, 4, 8 and 16 |
|---|---|
| Description | IGA assessed severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded sole, palms and scalp. |
| Time Frame | Baseline, Week 2, 4, 8 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 242 |
| Week 2 |
6.3
4.8%
|
15.2
6.4%
|
18.4
8.1%
|
4.7
1.9%
|
| Week 4 |
6.2
4.7%
|
25.2
10.6%
|
31.4
13.9%
|
18.9
7.8%
|
| Week 8 |
10.1
7.7%
|
35.8
15%
|
50.7
22.4%
|
28.5
11.8%
|
| Week 16 |
12.9
9.8%
|
34.8
14.6%
|
47.5
21%
|
38.8
16%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, PF-04965842 100 mg + Placebo Injection up to Week 16 |
|---|---|---|
| Comments | Week 16: Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 22.1 | |
| Confidence Interval |
(2-Sided) 95% 13.7 to 30.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, PF-04965842 200 mg + Placebo Injection up to Week 16 |
|---|---|---|
| Comments | Week 16: Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 35.0 | |
| Confidence Interval |
(2-Sided) 95% 26.3 to 43.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PF-04965842 100 mg + Placebo Injection up to Week 16, Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|
| Comments | Week 16: Difference in percentage (PF-04965842 versus dupilumab) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | -3.5 | |
| Confidence Interval |
(2-Sided) 95% -12.2 to 5.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PF-04965842 200 mg + Placebo Injection up to Week 16, Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|
| Comments | Week 16: Difference in percentage (PF-04965842 versus dupilumab) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 9.4 | |
| Confidence Interval |
(2-Sided) 95% 0.4 to 18.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving EASI Response >=75% Improvement From Baseline at Week 2, 4, 8 and 16 |
|---|---|
| Description | EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD. |
| Time Frame | Baseline, Week 2, 4, 8 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 242 |
| Week 2 |
10.9
8.3%
|
25.4
10.7%
|
30.0
13.3%
|
14.0
5.8%
|
| Week 4 |
15.6
11.9%
|
44.6
18.7%
|
57.4
25.4%
|
38.2
15.8%
|
| Week 8 |
18.6
14.2%
|
55.6
23.4%
|
67.9
30%
|
52.7
21.8%
|
| Week 16 |
30.6
23.4%
|
60.3
25.3%
|
71.0
31.4%
|
65.5
27.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, PF-04965842 100 mg + Placebo Injection up to Week 16 |
|---|---|---|
| Comments | Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in percentage |
| Estimated Value | 24.1 | |
| Confidence Interval |
(2-Sided) 95% 14.0 to 34.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, PF-04965842 200 mg + Placebo Injection up to Week 16 |
|---|---|---|
| Comments | Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 30.1 | |
| Confidence Interval |
(2-Sided) 95% 20.3 to 39.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo up to Week 16, Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|
| Comments | Week 16: Difference in percentage (PF-04965842 versus dupilumab) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | -2.7 | |
| Confidence Interval |
(2-Sided) 95% -9.6 to 4.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PF-04965842 100 mg + Placebo Injection up to Week 16, Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|
| Comments | Week 16: Difference in percentage (PF-04965842 versus dupilumab) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage |
| Estimated Value | 3.1 | |
| Confidence Interval |
(2-Sided) 95% -3.3 to 9.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving EASI Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16 |
|---|---|
| Description | EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD. |
| Time Frame | Baseline, Week 2, 4, 8, 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 242 |
| Week 2 |
21.9
16.7%
|
53.1
22.3%
|
60.5
26.8%
|
35.7
14.8%
|
| Week 4 |
39.8
30.4%
|
73.4
30.8%
|
78.5
34.7%
|
66.8
27.6%
|
| Week 8 |
48.8
37.3%
|
78.9
33.2%
|
88.4
39.1%
|
77.4
32%
|
| Week 12 |
52.7
40.2%
|
75.3
31.6%
|
86.3
38.2%
|
80.9
33.4%
|
| Week 16 |
57.3
43.7%
|
81.2
34.1%
|
87.3
38.6%
|
84.1
34.8%
|
| Title | Percentage of Participants Achieving EASI Response >=90% Improvement From Baseline at Week 2, 4, 8, 12 and 16 |
|---|---|
| Description | EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD. |
| Time Frame | Baseline, Week 2, 4, 8,12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 242 |
| Week 2 |
2.3
1.8%
|
8.3
3.5%
|
11.2
5%
|
2.6
1.1%
|
| Week 4 |
6.3
4.8%
|
20.2
8.5%
|
32.3
14.3%
|
12.2
5%
|
| Week 8 |
7.8
6%
|
30.6
12.9%
|
47.3
20.9%
|
24.3
10%
|
| Week 12 |
10.1
7.7%
|
36.6
15.4%
|
46.1
20.4%
|
34.9
14.4%
|
| Week 16 |
11.3
8.6%
|
38.0
16%
|
48.9
21.6%
|
38.8
16%
|
| Title | Percentage of Participants Achieving EASI Response =100% Improvement From Baseline at Week 2, 4, 8, 12 and 16 |
|---|---|
| Description | EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD. |
| Time Frame | Baseline, Week 2, 4, 8, 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 242 |
| Week 2 |
0
0%
|
1.3
0.5%
|
4.5
2%
|
0.4
0.2%
|
| Week 4 |
0
0%
|
2.6
1.1%
|
7.2
3.2%
|
2.5
1%
|
| Week 8 |
0
0%
|
6.0
2.5%
|
11.6
5.1%
|
2.1
0.9%
|
| Week 12 |
1.6
1.2%
|
8.1
3.4%
|
12.3
5.4%
|
6.6
2.7%
|
| Week 16 |
4.0
3.1%
|
12.7
5.3%
|
13.6
6%
|
5.2
2.1%
|
| Title | Time From Baseline to First Achieve at Least 4 Points Improvement in the Severity of Pruritus NRS |
|---|---|
| Description | Participants were asked to assess their worst pruritus/itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst possible itching), where higher scores indicated greater severity. |
| Time Frame | Baseline up to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Participants with a baseline numeric rating scale score for severity of pruritus >=4 were included in the analysis. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 130 | 236 | 226 | 240 |
| Median (95% Confidence Interval) [Days] |
NA
|
29.0
|
13.0
|
31.0
|
| Title | Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8, 12 and 16 |
|---|---|
| Description | 4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in the affected area of a body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Percent BSA for a body region was calculated as = total number of handprints in a body region * % surface area equivalent to 1 handprint. Overall % BSA for an individual: arithmetic mean of % BSA of all 4 body regions, ranges from 0 to 100%, with higher values representing greater severity of AD. |
| Time Frame | Baseline, Week 2, 4, 8, 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 242 |
| Change at Week 2 |
-7.6
|
-19.5
|
-21.4
|
-14.0
|
| Change at Week 4 |
-14.3
|
-26.8
|
-30.7
|
-24.0
|
| Change at Week 8 |
-16.2
|
-30.3
|
-36.4
|
-29.8
|
| Change at Week 12 |
-17.1
|
-31.6
|
-37.4
|
-32.5
|
| Change at Week 16 |
-19.6
|
-32.9
|
-39.0
|
-34.4
|
| Title | Percentage BSA at Week 18 and 20 |
|---|---|
| Description | 4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of participant's hand with fingers in a closed position) fitting in the affected area of a body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Percent BSA for a body region was calculated as = total number of handprints in a body region * % surface area equivalent to 1 handprint. Overall % BSA for an individual: arithmetic mean of % BSA of all 4 body regions, ranges from 0 to 100%, with higher values representing greater severity of AD. |
| Time Frame | Week 18 and 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set for post Week 16 included all randomized participants who received at least 1 dose of study medication post Week 16. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. |
| Measure Participants | 60 | 57 | 217 | 208 | 223 |
| Week 18 |
22.0
(23.67)
|
20.8
(22.7)
|
14.8
(19.3)
|
9.8
(13.6)
|
13.2
(16.4)
|
| Week 20 |
18.0
(21.2)
|
16.0
(19.7)
|
14.2
(19.0)
|
10.3
(14.2)
|
13.2
(16.3)
|
| Title | Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8, 12 and 16 |
|---|---|
| Description | Participant responded to the following question: "Overall, how would you describe your Atopic Dermatitis right now?" on a scale: 0= clear; 1= almost clear; 2= mild; 3= moderate; and 4= severe. Higher scores indicated more severity. |
| Time Frame | Baseline, Week 2, 4, 8, 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 241 |
| Change at Week 2 |
-0.5
|
-0.8
|
-1.0
|
-0.7
|
| Change at Week 4 |
-0.5
|
-1.0
|
-1.4
|
-1.1
|
| Change at Week 8 |
-0.6
|
-1.1
|
-1.5
|
-1.3
|
| Change at Week 12 |
-0.7
|
-1.2
|
-1.6
|
-1.3
|
| Change at Week 16 |
-0.7
|
-1.2
|
-1.6
|
-1.4
|
| Title | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 12 and 16 |
|---|---|
| Description | DLQI is a 10-item questionnaire that measures the impact of skin disease. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants. |
| Time Frame | Baseline, Week 2, 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 241 |
| Change at Week 2 |
-4.5
|
-6.7
|
-8.5
|
-6.7
|
| Change at Week 12 |
-6.2
|
-8.7
|
-11.0
|
-9.9
|
| Change at Week 16 |
-6.2
|
-9.0
|
-11.7
|
-10.8
|
| Title | DLQI at Week 20 |
|---|---|
| Description | DLQI is a 10-item questionnaire that measures the impact of skin disease. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participants. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set for post Week 16 included all randomized participants who received at least 1 dose of study medication post Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. |
| Measure Participants | 55 | 55 | 210 | 198 | 216 |
| Mean (Standard Deviation) [units on a scale] |
5.3
(5.3)
|
5.8
(5.7)
|
6.3
(5.8)
|
4.3
(4.7)
|
5.6
(4.8)
|
| Title | Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Index Value at Week 12 and 16 |
|---|---|
| Description | EQ-5D-5L: standardized participant completed questionnaire consisted of 2 components: a health state profile and an optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. US value sets (with all possible health states) was used for adults in the study, range from 1 to -0.109. Higher (positive) scores = better health state. |
| Time Frame | Baseline, Week 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 241 |
| Change at Week 12 |
0.051
|
0.101
|
0.127
|
0.104
|
| Change at Week 16 |
0.067
|
0.093
|
0.133
|
0.113
|
| Title | Change From Baseline in EQ-5D-5L Visual Analogue Scale (VAS) Score at Week 12 and 16 |
|---|---|
| Description | EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. |
| Time Frame | Baseline, Week 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 241 |
| Change at Week 12 |
7.975
|
11.337
|
17.373
|
14.939
|
| Change at Week 16 |
7.840
|
11.223
|
16.711
|
14.405
|
| Title | EQ-5D-5L- Index Value at Week 20 |
|---|---|
| Description | EQ-5D-5L: standardized participant completed questionnaire consisted of 2 components: a health state profile and an optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a participant responded "no problems" for each 5 dimensions, then health state was coded as "11111" with a predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. US value sets (with all possible health states) was used for adults in the study, range from 1 to -0.109. Higher (positive) scores = better health state. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set for post Week 16 included all randomized participants who received at least 1 dose of study medication post Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. |
| Measure Participants | 55 | 55 | 210 | 197 | 216 |
| Mean (Standard Deviation) [units on a scale] |
0.905
(0.097)
|
0.894
(0.122)
|
0.883
(0.124)
|
0.917
(0.109)
|
0.890
(0.109)
|
| Title | EQ-5D-5L- VAS Score at Week 20 |
|---|---|
| Description | EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set for post Week 16 included all randomized participants who received at least 1 dose of study medication post Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. |
| Measure Participants | 55 | 55 | 210 | 197 | 216 |
| Mean (Standard Deviation) [units on a scale] |
78.2
(16.3)
|
78.5
(20.2)
|
76.7
(19.5)
|
82.1
(17.1)
|
79.6
(18.0)
|
| Title | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety Scale at Week 12 and 16 |
|---|---|
| Description | HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-Anxiety (HADS-A) scale and HADS-Depression (HADS-D) scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety. |
| Time Frame | Baseline, Weeks 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 241 |
| Change at Week 12 |
-0.4
|
-1.2
|
-1.6
|
-1.4
|
| Change at Week 16 |
-0.4
|
-1.2
|
-2.0
|
-1.5
|
| Title | Change From Baseline in HADS - Depression Scale at Week 12 and 16 |
|---|---|
| Description | HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-D: sum of all 7 items resulted in score range of 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicating greater severity of depression symptoms. |
| Time Frame | Baseline, Week 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 241 |
| Change at Week 12 |
-0.3
|
-1.3
|
-1.6
|
-1.3
|
| Change at Week 16 |
-0.3
|
-1.0
|
-1.6
|
-1.2
|
| Title | HADS - Anxiety Scale at Week 20 |
|---|---|
| Description | HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set for post Week 16 included all randomized participants who received at least 1 dose of study medication post Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. |
| Measure Participants | 55 | 55 | 209 | 197 | 215 |
| Mean (Standard Deviation) [units on a scale] |
3.4
(3.2)
|
4.5
(4.5)
|
4.0
(3.8)
|
3.1
(3.1)
|
3.7
(3.5)
|
| Title | HADS - Depression Scale at Week 20 |
|---|---|
| Description | HADS: participant rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-D: sum of all 7 items resulted in score range of 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicating greater severity of depression symptoms. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set for post Week 16 included all randomized participants who received at least 1 dose of study medication post Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. |
| Measure Participants | 55 | 55 | 209 | 197 | 215 |
| Mean (Standard Deviation) [units on a scale] |
2.6
(3.4)
|
3.6
(3.7)
|
2.8
(3.2)
|
2.2
(3.1)
|
2.7
(3.3)
|
| Title | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 12 and 16 |
|---|---|
| Description | POEM is a 7-item participant reported outcome (PRO) measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item is scored as following: "no days (0)", "1-2 days (1)", "3-4 days (2)", "5-6 days (3)" and "every day (4)". The score ranges from 0 to 28, where higher score indicated greater severity. |
| Time Frame | Baseline, Week 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 241 |
| Change at Week 12 |
-5.1
|
-9.6
|
-12.6
|
-10.8
|
| Change at Week 16 |
-5.0
|
-9.2
|
-12.5
|
-10.8
|
| Title | POEM at Week 20 |
|---|---|
| Description | POEM is a 7-item participant reported outcome (PRO) measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item is scored as following: "no days (0)", "1-2 days (1)", "3-4 days (2)", "5-6 days (3)" and "every day (4)". The score ranges from 0 to 28, where higher score indicated greater severity. |
| Time Frame | Week 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set for post Week 16 included all randomized participants who received at least 1 dose of study medication post Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. |
| Measure Participants | 55 | 55 | 209 | 196 | 215 |
| Mean (Standard Deviation) [units on a scale] |
10.7
(6.8)
|
9.6
(7.8)
|
11.6
(7.7)
|
8.6
(7.0)
|
11.0
(6.9)
|
| Title | Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score Week 1 to Week 16 |
|---|---|
| Description | PSAAD is a daily participant reported symptom electronic diary. Participants rated their symptoms of AD over the past 24 hours, using 11 items (itchy skin, painful skin, dry skin, flaky skin, cracked skin, bumpy skin, red skin, discolored skin [lighter or darker], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Participant had to think about all the areas of their body affected by their skin condition and chose the number that best described their experience for each of the 11 items, from 0 (no symptoms) to 10 (extreme symptoms), higher scores signified worse skin condition. Total PSAAD score = arithmetic mean of 11 items, 0 (no symptoms) to 10 (extreme symptoms), where higher score = worse skin condition. |
| Time Frame | Baseline, Week 1 to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 130 | 237 | 225 | 241 |
| Change at Week 1 |
-0.5
|
-1.1
|
-1.3
|
-0.9
|
| Change at Week 2 |
-0.9
|
-1.8
|
-2.3
|
-1.6
|
| Change at Week 3 |
-1.1
|
-2.2
|
-2.8
|
-2.1
|
| Change at Week 4 |
-1.4
|
-2.4
|
-3.0
|
-2.4
|
| Change at Week 5 |
-1.5
|
-2.6
|
-3.2
|
-2.7
|
| Change at Week 6 |
-1.5
|
-2.6
|
-3.3
|
-2.8
|
| Change at Week 7 |
-1.6
|
-2.7
|
-3.4
|
-2.9
|
| Change at Week 8 |
-1.5
|
-2.7
|
-3.4
|
-3.0
|
| Change at Week 9 |
-1.7
|
-2.7
|
-3.5
|
-3.1
|
| Change at Week 10 |
-1.7
|
-2.7
|
-3.5
|
-3.1
|
| Change at Week 11 |
-1.6
|
-2.7
|
-3.5
|
-3.2
|
| Change at Week 12 |
-1.6
|
-2.7
|
-3.6
|
-3.2
|
| Change at Week 13 |
-1.7
|
-2.8
|
-3.7
|
-3.3
|
| Change at Week 14 |
-1.6
|
-2.8
|
-3.6
|
-3.4
|
| Change at Week 15 |
-1.7
|
-2.9
|
-3.6
|
-3.4
|
| Change at Week 16 |
-1.7
|
-2.8
|
-3.6
|
-3.4
|
| Title | PSAAD Total Score at Week 18 and 20 |
|---|---|
| Description | PSAAD is a daily participant reported symptom electronic diary. Participants rated their symptoms of AD over the past 24 hours, using 11 items (itchy skin, painful skin, dry skin, flaky skin, cracked skin, bumpy skin, red skin, discolored skin [lighter or darker], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Participant had to think about all the areas of their body affected by their skin condition and chose the number that best described their experience for each of the 11 items, from 0 (no symptoms) to 10 (extreme symptoms), higher scores signified worse skin condition. Total PSAAD score = arithmetic mean of 11 items, 0 (no symptoms) to 10 (extreme symptoms), where higher score = worse skin condition. |
| Time Frame | Week 18 and 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set for post Week 16 included all randomized participants who received at least 1 dose of study medication post Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. |
| Measure Participants | 54 | 54 | 202 | 202 | 218 |
| Week 18 |
2.6
(1.9)
|
3.0
(2.4)
|
2.2
(1.9)
|
1.7
(1.7)
|
1.8
(1.5)
|
| Week 20 |
2.5
(2.0)
|
2.6
(2.3)
|
2.2
(1.9)
|
1.8
(1.8)
|
2.0
(1.6)
|
| Title | Percentage of Participants With Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16 |
|---|---|
| Description | SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2,severe=3. The severity scores were summed to give B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale (VAS) where "0" = no itch/no sleeplessness and "10" = the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome. |
| Time Frame | Baseline, Week 2, 4, 8 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 242 |
| Week 2 |
10.2
7.8%
|
23.6
9.9%
|
38.4
17%
|
15.6
6.4%
|
| Week 4 |
18.6
14.2%
|
45.7
19.2%
|
61.6
27.3%
|
45.8
18.9%
|
| Week 8 |
20.2
15.4%
|
53.4
22.4%
|
71.6
31.7%
|
56.9
23.5%
|
| Week 12 |
27.3
20.8%
|
56.8
23.9%
|
72.3
32%
|
64.3
26.6%
|
| Week 16 |
33.3
25.4%
|
56.1
23.6%
|
68.8
30.4%
|
67.5
27.9%
|
| Title | Percentage of Participants With SCORAD Response >=75% Improvement From Baseline at Week 2, 4, 8 12 and 16 |
|---|---|
| Description | SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2,severe=3. The severity scores were summed to give B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale (VAS) where "0" = no itch/no sleeplessness and "10" = the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome. |
| Time Frame | Baseline, Week 2, 4, 8 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 242 |
| Week 2 |
1.6
1.2%
|
6.4
2.7%
|
8.5
3.8%
|
0.8
0.3%
|
| Week 4 |
3.1
2.4%
|
12.4
5.2%
|
25.4
11.2%
|
7.1
2.9%
|
| Week 8 |
3.1
2.4%
|
19.2
8.1%
|
41.3
18.3%
|
16.3
6.7%
|
| Week 12 |
6.3
4.8%
|
25.6
10.8%
|
39.3
17.4%
|
26.1
10.8%
|
| Week 16 |
10.6
8.1%
|
26.8
11.3%
|
40.3
17.8%
|
29.4
12.1%
|
| Title | Change From Baseline in SCORAD Visual Analogue Scale (VAS) of Itch and Sleep Loss at Week 2, 4, 8 12 and 16 |
|---|---|
| Description | SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2,severe=3. The severity scores were summed to give B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale (VAS) where "0" = no itch/no sleeplessness and "10" = the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome. |
| Time Frame | Baseline, Week 2, 4, 8 12 and 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 129 | 237 | 225 | 241 |
| Itch: Change at Week 2 |
-1.5
|
-2.9
|
-3.7
|
-2.4
|
| Itch: Change at Week 4 |
-2.2
|
-3.7
|
-4.6
|
-3.7
|
| Itch: Change at Week 8 |
-2.3
|
-3.9
|
-4.9
|
-4.2
|
| Itch: Change at Week 12 |
-2.4
|
-3.9
|
-5.0
|
-4.4
|
| Itch: Change at Week 16 |
-2.7
|
-3.8
|
-4.8
|
-4.5
|
| Sleep loss: Change at Week 2 |
-1.6
|
-2.6
|
-3.3
|
-2.3
|
| Sleep loss: Change at Week 4 |
-2.3
|
-3.4
|
-4.2
|
-3.4
|
| Sleep loss: Change at Week 8 |
-2.3
|
-3.6
|
-4.4
|
-3.9
|
| Sleep loss: Change at Week 12 |
-2.4
|
-3.7
|
-4.6
|
-4.2
|
| Sleep loss: Change at Week 16 |
-2.6
|
-3.7
|
-4.8
|
-4.3
|
| Title | SCORAD VAS of Itch and Sleep Loss at Week 18 and 20 |
|---|---|
| Description | SCORAD: scoring index for AD combining extent, severity, subjective symptoms. Extent (A): rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region- head and neck 9%; upper limbs 9% each; lower limbs 18% each; anterior trunk 18%; back 18%; 1% for genitals. The score for each body region was added to determine A (0-100). Severity (B): severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2,severe=3. The severity scores were summed to give B (0-18). Subjective symptoms (C): pruritus and sleep, each of these 2 were scored by participant/caregiver using visual analogue scale (VAS) where "0" = no itch/no sleeplessness and "10" = the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give 'C' (0-20). The SCORAD for an individual was calculated: A/5 + 7*B/2 + C; range from 0 to 103; higher values of SCORAD=worse outcome. |
| Time Frame | Week 18 and 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set for post Week 16 included all randomized participants who received at least 1 dose of study medication post Week 16. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points. |
| Arm/Group Title | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. |
| Measure Participants | 60 | 57 | 217 | 208 | 223 |
| Itch: Week 18 |
3.2
(2.6)
|
2.7
(2.2)
|
3.0
(2.5)
|
2.3
(2.2)
|
2.7
(2.2)
|
| Itch: Week 20 |
2.9
(2.4)
|
2.6
(2.4)
|
3.2
(2.6)
|
2.3
(2.3)
|
2.8
(2.2)
|
| Sleep loss: Week 18 |
2.2
(2.3)
|
2.3
(2.3)
|
2.1
(2.3)
|
1.6
(2.1)
|
1.8
(2.0)
|
| Sleep loss: Week 20 |
2.1
(2.2)
|
2.0
(2.3)
|
2.4
(2.6)
|
1.5
(2.1)
|
1.7
(2.1)
|
| Title | Least Square Mean of Number of Steroid-free Days From Baseline up to Week 16 |
|---|---|
| Description | Number of days when a corticosteroid as a concomitant medication was not used up to Week 16 is reported as Least square mean in this outcome measure. |
| Time Frame | Baseline up to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set till Week 16 included all randomized participants who received at least 1 dose of study medication up to Week 16. |
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 |
|---|---|---|---|---|
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. |
| Measure Participants | 131 | 238 | 226 | 242 |
| Least Squares Mean (95% Confidence Interval) [Days] |
21.8
|
30.2
|
33.6
|
28.1
|
Adverse Events
| Time Frame | For reporting arms till Week 16 analysis: Baseline up to Week 16; For reporting arms post Week 16 analysis: Week 16 to Week 24 (28 days after last dose of study drug) | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all randomized participants who received at least 1 dose of study medication. | |||||||||||||||||
| Arm/Group Title | Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 | |||||||||
| Arm/Group Description | Participants were randomized to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16. | Participants were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16. | Participants were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20. | Participants who were randomized to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20. | |||||||||
All Cause Mortality |
||||||||||||||||||
| Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
Serious Adverse Events |
||||||||||||||||||
| Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/131 (3.8%) | 6/238 (2.5%) | 2/226 (0.9%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||
| Pancytopenia | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Abdominal pain | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| General disorders | ||||||||||||||||||
| Chills | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pyrexia | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hepatobiliary disorders | ||||||||||||||||||
| Drug-induced liver injury | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Immune system disorders | ||||||||||||||||||
| Anaphylactic reaction | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Infections and infestations | ||||||||||||||||||
| Diarrhoea infectious | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Oral herpes | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pneumonia | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Enteritis infectious | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||
| Ankle fracture | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Meniscus injury | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Muscle injury | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tendon injury | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Investigations | ||||||||||||||||||
| Aspartate aminotransferase increased | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||
| Intervertebral disc protrusion | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||
| Invasive ductal breast carcinoma | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Renal and urinary disorders | ||||||||||||||||||
| Hydronephrosis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Nephrolithiasis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Ureterolithiasis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Urinary tract obstruction | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Reproductive system and breast disorders | ||||||||||||||||||
| Breast mass | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Uterine haemorrhage | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||
| Dyspnoea | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Interstitial lung disease | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||
| Dermatitis atopic | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Night sweats | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||
| Placebo up to Week 16 | PF-04965842 100 mg + Placebo Injection up to Week 16 | PF-04965842 200 mg + Placebo Injection up to Week 16 | Dupilumab 300 mg + Oral Placebo up to Week 16 | Placebo up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | Placebo up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | PF-04965842 100 mg + Placebo Injection up to Week 16 Then PF-04965842 100 mg Week 16 to 20 | PF-04965842 200 mg + Placebo Injection up to Week 16 Then PF-04965842 200 mg Week 16 to 20 | Dupilumab 300 mg + Oral Placebo up to Week 16 Then Oral Placebo Week 16 to 20 | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 68/131 (51.9%) | 121/238 (50.8%) | 140/226 (61.9%) | 120/242 (49.6%) | 13/60 (21.7%) | 16/57 (28.1%) | 50/217 (23%) | 45/208 (21.6%) | 31/223 (13.9%) | |||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||
| Anaemia | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Leukopenia | 0/131 (0%) | 1/238 (0.4%) | 3/226 (1.3%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Lymphadenitis | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Lymphadenopathy | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Lymphopenia | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Microcytic anaemia | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Thrombocytopenia | 0/131 (0%) | 0/238 (0%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Thrombocytosis | 0/131 (0%) | 2/238 (0.8%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Cardiac disorders | ||||||||||||||||||
| Arrhythmia | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Atrioventricular block first degree | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Bradycardia | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Defect conduction intraventricular | 2/131 (1.5%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Palpitations | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Sinus bradycardia | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 3/242 (1.2%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Ventricular extrasystoles | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Congenital, familial and genetic disorders | ||||||||||||||||||
| Dermoid cyst | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Congenital lacrimal passage anomaly | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Ear and labyrinth disorders | ||||||||||||||||||
| External ear inflammation | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Vertigo positional | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eye disorders | ||||||||||||||||||
| Asthenopia | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Blepharitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Conjunctival haemorrhage | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Conjunctival irritation | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Conjunctivitis allergic | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Dry eye | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Eye irritation | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eye pain | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eye pruritus | 1/131 (0.8%) | 1/238 (0.4%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eyelid oedema | 1/131 (0.8%) | 3/238 (1.3%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eyelid pain | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eyelids pruritus | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Lacrimation increased | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Noninfective conjunctivitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Ocular discomfort | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Ocular hyperaemia | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Presbyopia | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Swelling of eyelid | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Vision blurred | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eczema eyelids | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Eyelid cyst | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Abdominal discomfort | 0/131 (0%) | 0/238 (0%) | 3/226 (1.3%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Abdominal distension | 1/131 (0.8%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Abdominal pain | 1/131 (0.8%) | 0/238 (0%) | 3/226 (1.3%) | 3/242 (1.2%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Abdominal pain upper | 0/131 (0%) | 1/238 (0.4%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Anal pruritus | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Constipation | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Dental caries | 1/131 (0.8%) | 0/238 (0%) | 2/226 (0.9%) | 0/242 (0%) | 1/60 (1.7%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Diarrhoea | 4/131 (3.1%) | 4/238 (1.7%) | 4/226 (1.8%) | 3/242 (1.2%) | 0/60 (0%) | 2/57 (3.5%) | 3/217 (1.4%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Dyspepsia | 0/131 (0%) | 2/238 (0.8%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Faeces soft | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Flatulence | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Food poisoning | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Frequent bowel movements | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Gastritis | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Gastrooesophageal reflux disease | 1/131 (0.8%) | 2/238 (0.8%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Gingival pain | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Inguinal hernia | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Nausea | 2/131 (1.5%) | 10/238 (4.2%) | 25/226 (11.1%) | 7/242 (2.9%) | 0/60 (0%) | 5/57 (8.8%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Noninfective gingivitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tooth impacted | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Toothache | 1/131 (0.8%) | 1/238 (0.4%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Vomiting | 1/131 (0.8%) | 1/238 (0.4%) | 3/226 (1.3%) | 4/242 (1.7%) | 0/60 (0%) | 0/57 (0%) | 2/217 (0.9%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Gastritis erosive | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| General disorders | ||||||||||||||||||
| Asthenia | 0/131 (0%) | 2/238 (0.8%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Chest pain | 1/131 (0.8%) | 2/238 (0.8%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Chills | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Cyst | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Fatigue | 1/131 (0.8%) | 2/238 (0.8%) | 3/226 (1.3%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Feeling abnormal | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Feeling cold | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Feeling hot | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Inflammation | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Influenza like illness | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Injection site erythema | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Injection site oedema | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Injection site pain | 0/131 (0%) | 1/238 (0.4%) | 2/226 (0.9%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Injection site swelling | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Mass | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Malaise | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Medical device site rash | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Oedema peripheral | 0/131 (0%) | 1/238 (0.4%) | 2/226 (0.9%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pain | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Peripheral swelling | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pyrexia | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Swelling | 0/131 (0%) | 2/238 (0.8%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Swelling face | 0/131 (0%) | 2/238 (0.8%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Therapeutic response unexpected | 0/131 (0%) | 0/238 (0%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Xerosis | 0/131 (0%) | 2/238 (0.8%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hepatobiliary disorders | ||||||||||||||||||
| Gallbladder polyp | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Biliary colic | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hepatic function abnormal | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hepatic lesion | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hyperbilirubinaemia | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Liver disorder | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Immune system disorders | ||||||||||||||||||
| Allergy to chemicals | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Food allergy | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Hypersensitivity | 0/131 (0%) | 0/238 (0%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Seasonal allergy | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Infections and infestations | ||||||||||||||||||
| Abscess limb | 0/131 (0%) | 0/238 (0%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Bacterial vaginosis | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Body tinea | 1/131 (0.8%) | 1/238 (0.4%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Bronchitis | 1/131 (0.8%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 1/60 (1.7%) | 0/57 (0%) | 0/217 (0%) | 2/208 (1%) | 0/223 (0%) | |||||||||
| Cellulitis | 1/131 (0.8%) | 0/238 (0%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 2/217 (0.9%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Conjunctivitis | 3/131 (2.3%) | 2/238 (0.8%) | 3/226 (1.3%) | 15/242 (6.2%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 2/223 (0.9%) | |||||||||
| Conjunctivitis bacterial | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Cystitis | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Dermatophytosis of nail | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Ear infection | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eczema herpeticum | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eczema infected | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Epstein-Barr virus infection | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Erysipelas | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Folliculitis | 4/131 (3.1%) | 4/238 (1.7%) | 4/226 (1.8%) | 2/242 (0.8%) | 0/60 (0%) | 1/57 (1.8%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Fungal infection | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Fungal skin infection | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Furuncle | 2/131 (1.5%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 1/60 (1.7%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Gastroenteritis | 1/131 (0.8%) | 0/238 (0%) | 2/226 (0.9%) | 3/242 (1.2%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Gastroenteritis viral | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Gastrointestinal infection | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Gingivitis | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hand-foot-and-mouth disease | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Herpes dermatitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Herpes simplex | 1/131 (0.8%) | 5/238 (2.1%) | 8/226 (3.5%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 4/208 (1.9%) | 1/223 (0.4%) | |||||||||
| Herpes virus infection | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Herpes zoster | 0/131 (0%) | 1/238 (0.4%) | 4/226 (1.8%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Hordeolum | 1/131 (0.8%) | 2/238 (0.8%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Impetigo | 0/131 (0%) | 5/238 (2.1%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Influenza | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 1/60 (1.7%) | 0/57 (0%) | 2/217 (0.9%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Kaposi's varicelliform eruption | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Laryngitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Lower respiratory tract infection | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Malassezia infection | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Molluscum contagiosum | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Nasopharyngitis | 9/131 (6.9%) | 22/238 (9.2%) | 15/226 (6.6%) | 23/242 (9.5%) | 3/60 (5%) | 2/57 (3.5%) | 3/217 (1.4%) | 9/208 (4.3%) | 5/223 (2.2%) | |||||||||
| Ophthalmic herpes simplex | 1/131 (0.8%) | 0/238 (0%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Ophthalmic herpes zoster | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Oral herpes | 1/131 (0.8%) | 3/238 (1.3%) | 2/226 (0.9%) | 5/242 (2.1%) | 0/60 (0%) | 1/57 (1.8%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Otitis media | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Paronychia | 1/131 (0.8%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Perichondritis | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pharyngitis | 1/131 (0.8%) | 2/238 (0.8%) | 1/226 (0.4%) | 2/242 (0.8%) | 1/60 (1.7%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pharyngitis bacterial | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pharyngotonsillitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pulpitis dental | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pustule | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Rash pustular | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Respiratory tract infection | 1/131 (0.8%) | 2/238 (0.8%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Respiratory tract infection viral | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Rhinitis | 0/131 (0%) | 0/238 (0%) | 2/226 (0.9%) | 3/242 (1.2%) | 0/60 (0%) | 0/57 (0%) | 2/217 (0.9%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Sinusitis | 1/131 (0.8%) | 1/238 (0.4%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 1/57 (1.8%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Sinusitis bacterial | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Skin bacterial infection | 1/131 (0.8%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Skin candida | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Skin infection | 1/131 (0.8%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Staphylococcal skin infection | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Subcutaneous abscess | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tinea pedis | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tinea versicolour | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 1/57 (1.8%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tonsillitis | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tooth abscess | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tooth infection | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Upper respiratory tract infection | 6/131 (4.6%) | 12/238 (5%) | 9/226 (4%) | 9/242 (3.7%) | 1/60 (1.7%) | 0/57 (0%) | 6/217 (2.8%) | 5/208 (2.4%) | 7/223 (3.1%) | |||||||||
| Ureaplasma infection | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Urinary tract infection | 2/131 (1.5%) | 4/238 (1.7%) | 7/226 (3.1%) | 4/242 (1.7%) | 2/60 (3.3%) | 0/57 (0%) | 2/217 (0.9%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Urinary tract infection bacterial | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Viral infection | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Viral upper respiratory tract infection | 0/131 (0%) | 2/238 (0.8%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 1/57 (1.8%) | 2/217 (0.9%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Vulvovaginal mycotic infection | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Wound infection | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Asymptomatic bacteriuria | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Bronchitis bacterial | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 1/57 (1.8%) | 0/217 (0%) | 1/208 (0.5%) | 1/223 (0.4%) | |||||||||
| Bronchitis viral | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Gastrointestinal viral infection | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 1/60 (1.7%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Genital herpes simplex | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Nasal herpes | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 1/60 (1.7%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pneumonia bacterial | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Vulvovaginal candidiasis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||
| Animal bite | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Clavicle fracture | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Contusion | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eye injury | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Fall | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Foot fracture | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Head injury | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Joint injury | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Ligament sprain | 2/131 (1.5%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Limb injury | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Medication error | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Muscle strain | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Procedural pain | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Road traffic accident | 2/131 (1.5%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 1/57 (1.8%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Scapula fracture | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Skin abrasion | 0/131 (0%) | 1/238 (0.4%) | 3/226 (1.3%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Skin laceration | 1/131 (0.8%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 1/57 (1.8%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Soft tissue injury | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tooth fracture | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Traumatic haematoma | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Wound haemorrhage | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Arthropod bite | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Epicondylitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Humerus fracture | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Thermal burn | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Wound | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 1/57 (1.8%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Investigations | ||||||||||||||||||
| Activated partial thromboplastin time prolonged | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Alanine aminotransferase increased | 1/131 (0.8%) | 2/238 (0.8%) | 1/226 (0.4%) | 1/242 (0.4%) | 1/60 (1.7%) | 0/57 (0%) | 0/217 (0%) | 2/208 (1%) | 0/223 (0%) | |||||||||
| Aspartate aminotransferase increased | 1/131 (0.8%) | 2/238 (0.8%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Biopsy endometrium | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Blood bilirubin increased | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Blood cholesterol increased | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 1/223 (0.4%) | |||||||||
| Blood creatine phosphokinase increased | 3/131 (2.3%) | 7/238 (2.9%) | 6/226 (2.7%) | 2/242 (0.8%) | 1/60 (1.7%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Blood creatinine increased | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Blood lactate dehydrogenase increased | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Body temperature increased | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| C-reactive protein increased | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Cardiac murmur | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Ejection fraction decreased | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Electrocardiogram QT prolonged | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Electrocardiogram T wave amplitude increased | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Haematocrit decreased | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Haemoglobin decreased | 0/131 (0%) | 0/238 (0%) | 3/226 (1.3%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 2/208 (1%) | 0/223 (0%) | |||||||||
| Lipids increased | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Liver function test increased | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Natural killer cell count decreased | 0/131 (0%) | 2/238 (0.8%) | 4/226 (1.8%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Red blood cell count decreased | 0/131 (0%) | 0/238 (0%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| T-lymphocyte count decreased | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Transaminases increased | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Weight increased | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Blood pressure increased | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Blood urea increased | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Gamma-glutamyltransferase increased | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 1/60 (1.7%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Liver function test abnormal | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 1/57 (1.8%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Urine analysis abnormal | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eosinophil percentage increased | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||
| Decreased appetite | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Dyslipidaemia | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hypercholesterolaemia | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hyperglycaemia | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hypertriglyceridaemia | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hypophosphataemia | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Increased appetite | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Obesity | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Type 2 diabetes mellitus | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hyperuricaemia | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 2/208 (1%) | 0/223 (0%) | |||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||
| Arthralgia | 1/131 (0.8%) | 0/238 (0%) | 2/226 (0.9%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Arthritis | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Arthropathy | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Back pain | 5/131 (3.8%) | 0/238 (0%) | 1/226 (0.4%) | 7/242 (2.9%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Bursitis | 1/131 (0.8%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Foot deformity | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Mandibular mass | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Muscle spasms | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Muscle tightness | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Musculoskeletal pain | 2/131 (1.5%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Musculoskeletal stiffness | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Osteoarthritis | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pain in extremity | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Plantar fasciitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Rotator cuff syndrome | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Spinal pain | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Synovitis | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Temporomandibular joint syndrome | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tendonitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Joint swelling | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Intervertebral disc protrusion | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||
| Anogenital warts | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Skin papilloma | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Nervous system disorders | ||||||||||||||||||
| Dizziness | 2/131 (1.5%) | 4/238 (1.7%) | 7/226 (3.1%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 2/217 (0.9%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Dysaesthesia | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| External compression headache | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Headache | 6/131 (4.6%) | 10/238 (4.2%) | 15/226 (6.6%) | 13/242 (5.4%) | 1/60 (1.7%) | 1/57 (1.8%) | 2/217 (0.9%) | 0/208 (0%) | 2/223 (0.9%) | |||||||||
| Hypertonia | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hypoaesthesia | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Migraine | 1/131 (0.8%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Nerve compression | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Neuralgia | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Neuropathy peripheral | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Paraesthesia | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Parosmia | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Presyncope | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Somnolence | 0/131 (0%) | 3/238 (1.3%) | 2/226 (0.9%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tension headache | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||||||
| Pregnancy | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Psychiatric disorders | ||||||||||||||||||
| Anxiety | 0/131 (0%) | 2/238 (0.8%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Apathy | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Depression | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Depression suicidal | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Insomnia | 2/131 (1.5%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Irritability | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Libido decreased | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Mood swings | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Schizophrenia | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Renal and urinary disorders | ||||||||||||||||||
| Acute kidney injury | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Dysuria | 1/131 (0.8%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pollakiuria | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Polyuria | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Calculus urinary | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Haematuria | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Leukocyturia | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Urinary tract inflammation | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Reproductive system and breast disorders | ||||||||||||||||||
| Benign prostatic hyperplasia | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Dysmenorrhoea | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Erectile dysfunction | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hypomenorrhoea | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Menorrhagia | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Metrorrhagia | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Ovarian cyst | 0/131 (0%) | 0/238 (0%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Ovarian disorder | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Balanoposthitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Prostatitis | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||
| Asthma | 1/131 (0.8%) | 2/238 (0.8%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Cough | 2/131 (1.5%) | 3/238 (1.3%) | 4/226 (1.8%) | 3/242 (1.2%) | 0/60 (0%) | 0/57 (0%) | 3/217 (1.4%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Dyspnoea | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Epistaxis | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Nasal crusting | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Nasal dryness | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Oropharyngeal pain | 2/131 (1.5%) | 1/238 (0.4%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 1/223 (0.4%) | |||||||||
| Pulmonary mass | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Rhinorrhoea | 1/131 (0.8%) | 0/238 (0%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Sinus congestion | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Snoring | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Throat irritation | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Wheezing | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Sleep apnoea syndrome | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||
| Acne | 0/131 (0%) | 7/238 (2.9%) | 15/226 (6.6%) | 3/242 (1.2%) | 1/60 (1.7%) | 0/57 (0%) | 2/217 (0.9%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Actinic keratosis | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Alopecia | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Alopecia areata | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Angioedema | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Blister | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Dermatitis | 0/131 (0%) | 2/238 (0.8%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Dermatitis allergic | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Dermatitis atopic | 4/131 (3.1%) | 7/238 (2.9%) | 3/226 (1.3%) | 2/242 (0.8%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 4/208 (1.9%) | 2/223 (0.9%) | |||||||||
| Drug eruption | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Dyshidrotic eczema | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Eczema | 1/131 (0.8%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Erythema | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hyperhidrosis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hyperkeratosis | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Ingrowing nail | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Intertrigo | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Keratosis pilaris | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Nail bed disorder | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Nail fold inflammation | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Neurodermatitis | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Neutrophilic dermatosis | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Photosensitivity reaction | 1/131 (0.8%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pruritus | 1/131 (0.8%) | 3/238 (1.3%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 2/217 (0.9%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Pruritus allergic | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Rash | 1/131 (0.8%) | 2/238 (0.8%) | 2/226 (0.9%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Rash erythematous | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Rash papular | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 2/208 (1%) | 0/223 (0%) | |||||||||
| Seborrhoea | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Seborrhoeic dermatitis | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 2/208 (1%) | 0/223 (0%) | |||||||||
| Skin discolouration | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 1/242 (0.4%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Skin disorder | 2/131 (1.5%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Skin fissures | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Skin lesion | 0/131 (0%) | 1/238 (0.4%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Urticaria | 0/131 (0%) | 3/238 (1.3%) | 1/226 (0.4%) | 1/242 (0.4%) | 1/60 (1.7%) | 0/57 (0%) | 0/217 (0%) | 1/208 (0.5%) | 0/223 (0%) | |||||||||
| Dermatitis contact | 0/131 (0%) | 0/238 (0%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 1/217 (0.5%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Social circumstances | ||||||||||||||||||
| Victim of crime | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Surgical and medical procedures | ||||||||||||||||||
| Rotator cuff repair | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Tooth extraction | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Vascular disorders | ||||||||||||||||||
| Aortic stenosis | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Essential hypertension | 0/131 (0%) | 1/238 (0.4%) | 0/226 (0%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hot flush | 0/131 (0%) | 0/238 (0%) | 1/226 (0.4%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 0/208 (0%) | 0/223 (0%) | |||||||||
| Hypertension | 0/131 (0%) | 2/238 (0.8%) | 3/226 (1.3%) | 0/242 (0%) | 0/60 (0%) | 0/57 (0%) | 0/217 (0%) | 2/208 (1%) | 1/223 (0.4%) | |||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03720470
Other Study ID Numbers:
- B7451029
- COMPARE
- 2018-002573-21
First Posted:
Oct 25, 2018
Last Update Posted:
Jan 19, 2021
Last Verified:
Dec 1, 2020