IMPACT-PS: Study to Evaluate the Efficacy and Safety of JTE-451 in Subjects With Moderate to Severe Plaque Psoriasis

• Sponsor: Akros Pharma Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03832738
• Collaborator: (none)
• Enrollment: 152
• Locations: 33
• Arms: 3
• Actual Duration (Months): 13.8
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Study to evaluate the efficacy and safety of JTE-451 administered for 16 weeks in subjects with moderate to severe plaque psoriasis.

Condition or Disease	Intervention/Treatment	Phase
Plaque Psoriasis; Psoriasis; Skin Diseases	Drug: JTE-451 Tablets; Drug: Placebo Tablets	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of JTE-451 Administered for 16 Weeks in Subjects With Moderate to Severe Plaque Psoriasis (IMPACT-PS)
• Actual Study Start Date: Jan 17, 2019
• Actual Primary Completion Date: Mar 13, 2020
• Actual Study Completion Date: Mar 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JTE-451 Dose 1 JTE-451 Tablets Dose 1 daily for 16 weeks.	Drug: JTE-451 Tablets; Active drug tablets containing JTE-451
Experimental: JTE-451 Dose 2 JTE-451 Tablets Dose 2 daily for 16 weeks.	Drug: JTE-451 Tablets; Active drug tablets containing JTE-451
Placebo Comparator: Placebo Placebo Tablets daily for 16 weeks.	Drug: Placebo Tablets; Placebo tablets matching in appearance to the active drug tablets

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Achieving a Minimum 75% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-75) at End-of-treatment (EOT) [End of Treatment (Up to 16 Weeks)]

   The psoriasis area and severity index (PASI) combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. The PASI-75 response rate is defined as at least 75 percent (%) reduction in PASI score at EOT (up to 16 weeks) relative to Baseline.

Secondary Outcome Measures

1. Percentage of Subjects Achieving a Minimum 50% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-50) at EOT [End of Treatment (Up to 16 Weeks)]

   The PASI combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. The PASI-50 response rate is defined as at least 50 percent (%) reduction in PASI score at EOT (up to 16 weeks) relative to Baseline.

2. Percentage of Subjects Achieving a Minimum 90% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-90) at EOT [End of Treatment (Up to 16 Weeks)]

   The PASI combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. The PASI-90 response rate is defined as at least 90 percent (%) reduction in PASI score at EOT (up to 16 weeks) relative to Baseline.

3. Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at EOT [End of Treatment (Up to 16 Weeks)]

   The PASI combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. Percent change from baseline to EOT (up to 16 weeks) in PASI score was calculated by taking the PASI score at EOT and subtracting the baseline PASI score, then dividing by the baseline PASI score and multiplying by 100.

4. Percentage of Subjects Who Achieved Static Physician's Global Assessment (sPGA) Score of 0 or 1 at EOT [End of Treatment (Up to 16 Weeks)]

   The sPGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the redness, thickness and scaling across all psoriatic lesions. Average redness, thickness and scaling are scored separately over the whole body according to a 5-point severity scale (0 [no symptoms] to 4 [severe symptoms]). The total score is calculated as average of the 3 severity (redness, thickness and scaling) scores and rounded to the nearest whole number score to determine the sPGA score (0=cleared; 1=minimal; 2=mild; 3=moderate; and 4=severe). For this outcome measure, at EOT (up to 16 weeks), a score of 0 means no symptoms of psoriasis and a score of 1 means minimal symptoms of psoriasis.

5. Change From Baseline in Static Physician's Global Assessment (sPGA) Score at EOT [End of Treatment (Up to 16 Weeks)]

   The sPGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the redness, thickness and scaling across all psoriatic lesions. Average redness, thickness and scaling are scored separately over the whole body according to a 5-point severity scale (0 [no symptoms] to 4 [severe symptoms]). The total score is calculated as average of the 3 severity (redness, thickness and scaling) scores and rounded to the nearest whole number score to determine the sPGA score (0=cleared; 1=minimal; 2=mild; 3=moderate; and 4=severe). Change from baseline to EOT (up to 16 weeks) in sPGA score was calculated by taking the sPGA score at EOT and subtracting the baseline sPGA score.

6. Percent Change From Baseline in Psoriasis Body Surface Area (BSA) at EOT [End of Treatment (Up to 16 Weeks)]

   The total body surface area (BSA) affected by plaque-type psoriasis was obtained from the percentages of areas affected, including head, trunk, upper limbs and lower limbs. Each reported percentage was multiplied by its respective body region corresponding factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4) and the resulting 4 values were added up to obtain the total psoriasis BSA (Range: 0 to 100). BSA (%)=0.1Sh+0.2Su+0.3St+0.4Sl, where S=body region surface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs. Percent change from baseline to EOT (up to 16 weeks) in BSA was calculated by taking the EOT BSA and subtracting the baseline BSA, then dividing by the baseline BSA and multiplying by 100. A negative change from baseline at EOT indicates a reduction in the Psoriasis BSA compared to the baseline.

7. Change From Baseline in the Skindex-16 Overall Score at EOT [End of Treatment (Up to 16 Weeks)]

   Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Overall scale score is an average of 16 items expressed in a linear scale from 0 to 100. Change from baseline to EOT (up to 16 weeks) in the Skindex-16 Overall Score was calculated by taking the EOT Skindex-16 Overall Score and subtracting the baseline Skindex-16 Overall Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline.

8. Change From Baseline in the Skindex-16 Symptom Scale Scores at EOT [End of Treatment (Up to 16 Weeks)]

   Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Symptoms scale score is an average of items 1 to 4 expressed in a linear scale from 0 to 100. Change from baseline to EOT (up to 16 weeks) in the Skindex-16 Symptoms Scale Score was calculated by taking the EOT Skindex-16 Symptoms Scale Score and subtracting the baseline Skindex-16 Symptoms Scale Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline.

9. Change From Baseline in the Skindex-16 Emotions Scale Scores at EOT [End of Treatment (Up to 16 Weeks)]

   Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Emotions scale score is an average of items 5 to 11 expressed in a linear scale from 0 to 100. Change from baseline to EOT (up to 16 weeks) in the Skindex-16 Emotions Scale Score was calculated by taking the EOT Skindex-16 Emotions Scale Score and subtracting the baseline Skindex-16 Emotions Scale Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline.

10. Change From Baseline in the Skindex-16 Functioning Scale Scores at EOT [End of Treatment (Up to 16 Weeks)]

    Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Functioning scale score is an average of items 12 to 16 expressed in a linear scale from 0 to 100. Change from baseline to EOT (up to 16 weeks) in the Skindex-16 Functioning Scale Score was calculated by taking the EOT Skindex-16 Functioning Scale Score and subtracting the baseline Skindex-16 Functioning Scale Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline.

11. Change From Baseline in Itch Numeric Rating Scale (NRS) at EOT [End of Treatment (Up to 16 Weeks)]

    The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. The Itch NRS scores were recorded by the subject using the e-diary once daily from screening through the last visit. Change from baseline to EOT (up to 16 weeks) in the Itch NRS Score was calculated by taking the Itch NRS Score (weekly average) at EOT and subtracting the baseline Itch NRS Score (weekly average).

12. Number of Subjects With Treatment-emergent Adverse Events [Follow-up (Up to 20 Weeks)]

    Subjects in the Safety Population (151, randomized subjects who received at least one dose of study drug). The treatment-emergent adverse event (TEAE) is defined as one of the following: An adverse event (AE) that occurred during the treatment period or the follow-up period. In the process of collecting the onset dates of AEs, an AE that occurs after the initiation of trial medication on Day 1 (the first day of the treatment period) should be treated as a TEAE. All AEs occurring on the day of first dose will be considered as TEAE if the time of AE occurrence relative to the dosing is unknown. An AE present prior to the treatment period that worsened in severity during the treatment period or the follow-up period. Any events that are present prior to the treatment period and have recovered, but recurred during the treatment period or the follow-up period should be considered as new TEAEs.

13. JTE-451 Trough Plasma Concentrations at Week 16 [Week 16]

    Trough plasma concentration is the measured concentration at the end of a dosing interval at steady state (taken directly before next administration). Blood samples were collected at specific timepoints to measure trough plasma concentration of JTE-451 in the pharmacokinetic (PK) population.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have had a history of moderate to severe plaque psoriasis for at least 6 months prior to Visit 1;

• Subjects with moderate to severe plaque psoriasis covering ≥10% body surface area (BSA), with a psoriasis area and severity index (PASI) ≥12 and static Physician's Global Assessment (sPGA) score ≥3 at Visit 1 and Visit 2

Exclusion Criteria:

• History of discontinuation of biologic therapies (including marketed and investigational drugs) directly targeting Interleukin (IL)-17A, IL-17A/F, IL-17 receptor A, IL-12/IL-23p40 or IL-23p19 due to lack of efficacy, according to the Investigator's judgment;

• Prior exposure to retinoid-related orphan receptor (ROR)-γ inhibitors;

• Presence of erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis or other skin conditions (e.g., clinically-significant eczema or severe acne) at Visit 1;

• History or presence of itch due to underlying conditions other than plaque psoriasis which cause or influence pruritus of the skin within 12 months prior to Visit 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Science Institute	Santa Monica	California	United States	90404
2	Advanced Dermatology and Skin Cancer Specialists	Temecula	California	United States	92592
3	Dawes Fretzin Clinical Research Group, LLC	Indianapolis	Indiana	United States	46250
4	Central Sooner Research	Norman	Oklahoma	United States	73071
5	Rhode Island Hospital	Providence	Rhode Island	United States	02903
6	Health Concepts	Rapid City	South Dakota	United States	57702
7	Wiseman Dermatology Research Inc.	Winnipeg	Manitoba	Canada	R3M 3Z4
8	SimcoDerm Medical and Surgical Dermatology Center	Barrie	Ontario	Canada	L4M 7G1
9	SKiN Health	Cobourg	Ontario	Canada	K9A 0B3
10	Research Toronto	Toronto	Ontario	Canada	M4W 2N2
11	K. Papp Clinical Research	Waterloo	Ontario	Canada	N2J 1C4
12	Diex Research Sherbrooke Inc.	Sherbrooke	Quebec	Canada	J1L 0H8
13	Szpital Uniwersytecki nr 1 im. Dr. A. Jurasza w Bydgoszczy, Klinika Dermatologii, Chorob Prenoszonych Droga Plciowa	Bydgoszcz		Poland	85-094
14	Copernicus Podmiot Leczniczy Sp. z o.o., Oddzial Dermatologii	Gdansk		Poland	80-152
15	Prywatny Gabinet Dermatologiczny Elzbieta Klujszo	Kielce		Poland	25-316
16	Centrum Nowoczesnych Terapii "Dobry Lekarz" Spolka z orgraniczona odpowiedzialnoscia	Krakow		Poland	31-011
17	Centrum Terapii Wspolczesnej J.M. Jasnorzewska Spolka Komandytowo-Akeyjna	Lodz		Poland	90-242
18	ETG Lodz	Lodz		Poland	90-302
19	Dermoklinika - Centrum Medyczne s.c., M. Kierstan, J. Narbutt, A. Lesiak	Lodz		Poland	90-436
20	ETG Lublin	Lublin		Poland	20-412
21	Centrum Medyczne Grunwald	Poznan		Poland	60-369
22	Solumed Centrum Medyczne	Poznan		Poland	60-529
23	Kliniczny Szpital Wojewodzki nr 1 im. Fryderyka Chopina w Rzeszowie, Klinika Dermatologii	Rzeszow		Poland	35-055
24	ETG Siedlce	Siedlce		Poland	08-110
25	ETG Skierniewice	Skierniewice		Poland	96-100
26	Clinical Research Group Sp. z o.o.	Warszawa		Poland	01-142
27	Dorota Bystrzanowska "High-Med" Przychodnia Specjalistyczna	Warszawa		Poland	01-817
28	Carpe Diem Centrum Medycyny Estetycznej	Warszawa		Poland	02-661
29	Royalderm Agnieszka Nawrocka	Warszawa		Poland	02-692
30	ETG Warszawa	Warszawa		Poland	02-777
31	CITYCLINIC Przychodnia Psychologiczno-Lekarska Matusiak Spolka Partnerska	Wroclaw		Poland	50-566
32	DERMMEDICA Sp. z o.o.	Wrocław		Poland	51-318
33	ETG Zamosc	Zamosc		Poland	22-400

Sponsors and Collaborators

• Akros Pharma Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 24, 2019
• Statistical Analysis Plan - Mar 30, 2020

More Information

Publications

None provided.

• Responsible Party: Akros Pharma Inc.
• ClinicalTrials.gov Identifier: NCT03832738
• Other Study ID Numbers: AE451-G-18-004
• First Posted: Feb 6, 2019
• Last Update Posted: Aug 20, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Akros Pharma Inc.: JTE-451; Psoriasis; Plaque psoriasis; IMPACT-PS
• Additional relevant MeSH terms: Psoriasis; Skin Diseases

Study Results

Participant Flow

Recruitment Details	Written informed consent was obtained prior to performing any study-related procedures. A copy of the informed consent was provided to each subject enrolled in this study. To qualify for the study, subjects were required to satisfy defined criteria.
Pre-assignment Detail	Following informed consent signing, screening procedures to confirm eligibility were performed. Intent-to-Treat (ITT) Population - 152 subjects Safety Population - 151 subjects Pharmacokinetic (PK) Population - 101 subjects

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Period Title: Overall Study
STARTED	51	50	51
COMPLETED	43	38	32
NOT COMPLETED	8	12	19

Baseline Characteristics

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily	Total
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks	Total of all reporting groups
Overall Participants	51	50	51	152
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	47 92.2%	46 92%	46 90.2%	139 91.4%
>=65 years	4 7.8%	4 8%	5 9.8%	13 8.6%
Sex: Female, Male (Count of Participants)
Female	13 25.5%	21 42%	16 31.4%	50 32.9%
Male	38 74.5%	29 58%	35 68.6%	102 67.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 2%	1 2%	2 1.3%
Not Hispanic or Latino	51 100%	49 98%	50 98%	150 98.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	2 4%	2 3.9%	4 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 2%	0 0%	1 0.7%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	51 100%	47 94%	49 96.1%	147 96.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	5 9.8%	5 10%	3 5.9%	13 8.6%
United States	2 3.9%	7 14%	6 11.8%	15 9.9%
Poland	44 86.3%	38 76%	42 82.4%	124 81.6%
Prior exposure to biologics therapy (Count of Participants)
Had prior biologics therapy	11 21.6%	15 30%	13 25.5%	39 25.7%
No prior biologics therapy	40 78.4%	35 70%	38 74.5%	113 74.3%
Body weight (Count of Participants)
Below 90 kg	25 49%	24 48%	25 49%	74 48.7%
90 kg or above	26 51%	26 52%	26 51%	78 51.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Achieving a Minimum 75% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-75) at End-of-treatment (EOT)
Description	The psoriasis area and severity index (PASI) combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. The PASI-75 response rate is defined as at least 75 percent (%) reduction in PASI score at EOT (up to 16 weeks) relative to Baseline.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	51
Number [% of subjects achieving PASI-75]	11.8	22.0	7.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	JTE-451 200 mg Twice Daily, Placebo Twice Daily
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.558
	Comments	p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; 0.39 to 5.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	JTE-451 400 mg Twice Daily, Placebo Twice Daily
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments	p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.74
	Confidence Interval	(2-Sided) 95%; 1.07 to 13.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Subjects Achieving a Minimum 50% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-50) at EOT
Description	The PASI combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. The PASI-50 response rate is defined as at least 50 percent (%) reduction in PASI score at EOT (up to 16 weeks) relative to Baseline.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	51
Number [% of subjects achieving PASI-50]	33.3	42.0	17.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	JTE-451 200 mg Twice Daily, Placebo Twice Daily
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.086
	Comments	p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.26
	Confidence Interval	(2-Sided) 95%; 0.89 to 5.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	JTE-451 400 mg Twice Daily, Placebo Twice Daily
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments	p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.76
	Confidence Interval	(2-Sided) 95%; 1.45 to 9.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Subjects Achieving a Minimum 90% Improvement From Baseline in the Psoriasis Area and Severity Index (PASI-90) at EOT
Description	The PASI combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. The PASI-90 response rate is defined as at least 90 percent (%) reduction in PASI score at EOT (up to 16 weeks) relative to Baseline.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	51
Number [% of subjects achieving PASI-90]	2.0	6.0	2.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	JTE-451 200 mg Twice Daily, Placebo Twice Daily
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	>0.999
	Comments	p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1
	Confidence Interval	(2-Sided) 95%; 0.06 to 17.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	JTE-451 400 mg Twice Daily, Placebo Twice Daily
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.244
	Comments	p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.86
	Confidence Interval	(2-Sided) 95%; 0.36 to 41.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at EOT
Description	The PASI combines the assessment of the severity of lesions (scaling, redness and plaque thickness) and the area affected into a single score in the range of 0.0 (no disease) to 72.0 (maximal disease). The body is divided into four sections: (1) Head and neck; (2) Upper limbs; (3) Trunk (including axillae and groin); and (4) Lower limbs (including buttocks). The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. Percent change from baseline to EOT (up to 16 weeks) in PASI score was calculated by taking the PASI score at EOT and subtracting the baseline PASI score, then dividing by the baseline PASI score and multiplying by 100.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	48
Mean (Standard Deviation) [% change in PASI Score]	-30.33 (40.971)	-37.89 (37.896)	-17.53 (34.701)

5. Secondary Outcome

Title	Percentage of Subjects Who Achieved Static Physician's Global Assessment (sPGA) Score of 0 or 1 at EOT
Description	The sPGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the redness, thickness and scaling across all psoriatic lesions. Average redness, thickness and scaling are scored separately over the whole body according to a 5-point severity scale (0 [no symptoms] to 4 [severe symptoms]). The total score is calculated as average of the 3 severity (redness, thickness and scaling) scores and rounded to the nearest whole number score to determine the sPGA score (0=cleared; 1=minimal; 2=mild; 3=moderate; and 4=severe). For this outcome measure, at EOT (up to 16 weeks), a score of 0 means no symptoms of psoriasis and a score of 1 means minimal symptoms of psoriasis.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	51
Number [% of subjects achieving sPGA 0 or 1]	25.5	28.0	5.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	JTE-451 200 mg Twice Daily, Placebo Twice Daily
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments	p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.21
	Confidence Interval	(2-Sided) 95%; 1.38 to 19.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	JTE-451 400 mg Twice Daily, Placebo Twice Daily
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.35
	Confidence Interval	(2-Sided) 95%; 1.86 to 29.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Static Physician's Global Assessment (sPGA) Score at EOT
Description	The sPGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the redness, thickness and scaling across all psoriatic lesions. Average redness, thickness and scaling are scored separately over the whole body according to a 5-point severity scale (0 [no symptoms] to 4 [severe symptoms]). The total score is calculated as average of the 3 severity (redness, thickness and scaling) scores and rounded to the nearest whole number score to determine the sPGA score (0=cleared; 1=minimal; 2=mild; 3=moderate; and 4=severe). Change from baseline to EOT (up to 16 weeks) in sPGA score was calculated by taking the sPGA score at EOT and subtracting the baseline sPGA score.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	48
Mean (Standard Deviation) [score on a scale]	-0.96 (0.848)	-1.02 (0.869)	-0.54 (0.713)

7. Secondary Outcome

Title	Percent Change From Baseline in Psoriasis Body Surface Area (BSA) at EOT
Description	The total body surface area (BSA) affected by plaque-type psoriasis was obtained from the percentages of areas affected, including head, trunk, upper limbs and lower limbs. Each reported percentage was multiplied by its respective body region corresponding factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4) and the resulting 4 values were added up to obtain the total psoriasis BSA (Range: 0 to 100). BSA (%)=0.1Sh+0.2Su+0.3St+0.4Sl, where S=body region surface area with psoriasis: h=head; u=upper limbs; t=trunk; l=lower limbs. Percent change from baseline to EOT (up to 16 weeks) in BSA was calculated by taking the EOT BSA and subtracting the baseline BSA, then dividing by the baseline BSA and multiplying by 100. A negative change from baseline at EOT indicates a reduction in the Psoriasis BSA compared to the baseline.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	48
Mean (Standard Deviation) [% Change in Psoriasis BSA]	-18.67 (39.582)	-19.03 (48.696)	-5.74 (38.707)

8. Secondary Outcome

Title	Change From Baseline in the Skindex-16 Overall Score at EOT
Description	Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Overall scale score is an average of 16 items expressed in a linear scale from 0 to 100. Change from baseline to EOT (up to 16 weeks) in the Skindex-16 Overall Score was calculated by taking the EOT Skindex-16 Overall Score and subtracting the baseline Skindex-16 Overall Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	48
Mean (Standard Deviation) [score on a scale]	-10.029 (23.2635)	-10.896 (26.7910)	-3.386 (20.8617)

9. Secondary Outcome

Title	Change From Baseline in the Skindex-16 Symptom Scale Scores at EOT
Description	Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Symptoms scale score is an average of items 1 to 4 expressed in a linear scale from 0 to 100. Change from baseline to EOT (up to 16 weeks) in the Skindex-16 Symptoms Scale Score was calculated by taking the EOT Skindex-16 Symptoms Scale Score and subtracting the baseline Skindex-16 Symptoms Scale Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	48
Mean (Standard Deviation) [score on a scale]	-8.905 (34.2989)	-11.500 (31.5148)	-2.170 (26.0563)

10. Secondary Outcome

Title	Change From Baseline in the Skindex-16 Emotions Scale Scores at EOT
Description	Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses to the Skindex-16 are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Emotions scale score is an average of items 5 to 11 expressed in a linear scale from 0 to 100. Change from baseline to EOT (up to 16 weeks) in the Skindex-16 Emotions Scale Score was calculated by taking the EOT Skindex-16 Emotions Scale Score and subtracting the baseline Skindex-16 Emotions Scale Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	48
Mean (Standard Deviation) [score on a scale]	-10.411 (21.8268)	-13.143 (28.4467)	-5.953 (22.6358)

11. Secondary Outcome

Title	Change From Baseline in the Skindex-16 Functioning Scale Scores at EOT
Description	Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Each raw score is multiplied by 16.667 to transform all responses to a linear scale from 0 (no effect) to 100 (effect experienced all the time). Responses are categorized into 3 subscales: symptom, emotional & functional; their respective scores are expressed in a linear scale from 0 to 100. Functioning scale score is an average of items 12 to 16 expressed in a linear scale from 0 to 100. Change from baseline to EOT (up to 16 weeks) in the Skindex-16 Functioning Scale Score was calculated by taking the EOT Skindex-16 Functioning Scale Score and subtracting the baseline Skindex-16 Functioning Scale Score. A negative change from baseline at EOT indicates an improvement in the subject's condition compared to the baseline.
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	48
Mean (Standard Deviation) [score on a scale]	-10.392 (23.5294)	-7.267 (27.6823)	-0.764 (20.1090)

12. Secondary Outcome

Title	Change From Baseline in Itch Numeric Rating Scale (NRS) at EOT
Description	The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. The Itch NRS scores were recorded by the subject using the e-diary once daily from screening through the last visit. Change from baseline to EOT (up to 16 weeks) in the Itch NRS Score was calculated by taking the Itch NRS Score (weekly average) at EOT and subtracting the baseline Itch NRS Score (weekly average).
Time Frame	End of Treatment (Up to 16 Weeks)

Outcome Measure Data

Analysis Population Description

Subjects in the ITT Population at the EOT. The EOT value is defined as the last assessment during the treatment period (from the first dose of study drug to the last dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	48
Mean (Standard Deviation) [score on a scale]	-1.302 (2.8165)	-1.537 (3.2634)	-0.547 (2.4239)

13. Secondary Outcome

Title	Number of Subjects With Treatment-emergent Adverse Events
Description	Subjects in the Safety Population (151, randomized subjects who received at least one dose of study drug). The treatment-emergent adverse event (TEAE) is defined as one of the following: An adverse event (AE) that occurred during the treatment period or the follow-up period. In the process of collecting the onset dates of AEs, an AE that occurs after the initiation of trial medication on Day 1 (the first day of the treatment period) should be treated as a TEAE. All AEs occurring on the day of first dose will be considered as TEAE if the time of AE occurrence relative to the dosing is unknown. An AE present prior to the treatment period that worsened in severity during the treatment period or the follow-up period. Any events that are present prior to the treatment period and have recovered, but recurred during the treatment period or the follow-up period should be considered as new TEAEs.
Time Frame	Follow-up (Up to 20 Weeks)

Outcome Measure Data

Analysis Population Description

Safety Population (151, randomized subjects who received at least one dose of study drug).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily	Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)	Placebo Tablets orally twice daily for 16 weeks
Measure Participants	51	50	50
Number of subjects with TEAEs	27 52.9%	28 56%	25 49%
Number of subjects with no TEAEs	24 47.1%	22 44%	25 49%

14. Secondary Outcome

Title	JTE-451 Trough Plasma Concentrations at Week 16
Description	Trough plasma concentration is the measured concentration at the end of a dosing interval at steady state (taken directly before next administration). Blood samples were collected at specific timepoints to measure trough plasma concentration of JTE-451 in the pharmacokinetic (PK) population.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Subjects (75 subjects) in the PK population at Week 16 with available trough plasma concentrations of JTE-451 (subjects who received at least one dose of JTE-451 and have at least one usable JTE-451 plasma concentration measurement at Week 16).

Arm/Group Title	JTE-451 200 mg Twice Daily	JTE-451 400 mg Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)	JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)
Measure Participants	42	33
Mean (Standard Deviation) [ng/mL]	575 (704)	1210 (1660)

Adverse Events

Time Frame	Up to 20 Weeks
Adverse Event Reporting Description	Subjects in the Safety Population (151, randomized subjects who received at least one dose of study drug).
Arm/Group Title	JTE-451 200 mg Twice Daily		JTE-451 400 mg Twice Daily		Placebo Twice Daily
Arm/Group Description	JTE-451 200 mg orally twice daily for 16 weeks (total daily dose - 400 mg)		JTE-451 400 mg orally twice daily for 16 weeks (total daily dose - 800 mg)		Placebo Tablets orally twice daily for 16 weeks
All Cause Mortality
	JTE-451 200 mg Twice Daily		JTE-451 400 mg Twice Daily		Placebo Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/50 (0%)		0/50 (0%)
Serious Adverse Events
	JTE-451 200 mg Twice Daily		JTE-451 400 mg Twice Daily		Placebo Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/51 (2%)		2/50 (4%)		1/50 (2%)
Cardiac disorders
Atrial fibrillation	0/51 (0%)	0	1/50 (2%)	1	0/50 (0%)	0
Infections and infestations
Breast Abscess	1/51 (2%)	1	0/50 (0%)	0	0/50 (0%)	0
Gastroenteritis	0/51 (0%)	0	1/50 (2%)	1	0/50 (0%)	0
Skin and subcutaneous tissue disorders
Psoriasis	0/51 (0%)	0	0/50 (0%)	0	1/50 (2%)	1
Other (Not Including Serious) Adverse Events
	JTE-451 200 mg Twice Daily		JTE-451 400 mg Twice Daily		Placebo Twice Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/51 (39.2%)		22/50 (44%)		17/50 (34%)
Gastrointestinal disorders
Abdominal Pain	2/51 (3.9%)	2	2/50 (4%)	2	1/50 (2%)	1
Abdominal Pain Upper	4/51 (7.8%)	4	2/50 (4%)	3	0/50 (0%)	0
Diarrhoea	7/51 (13.7%)	13	19/50 (38%)	30	3/50 (6%)	3
Infections and infestations
Nasopharyngitis	3/51 (5.9%)	4	2/50 (4%)	2	5/50 (10%)	5
Pharyngitis	1/51 (2%)	1	0/50 (0%)	0	2/50 (4%)	2
Sinusitis	0/51 (0%)	0	0/50 (0%)	0	2/50 (4%)	2
Upper Respiratory Tract Infection	2/51 (3.9%)	2	3/50 (6%)	3	4/50 (8%)	4
Urinary Tract Infection	3/51 (5.9%)	4	3/50 (6%)	3	0/50 (0%)	0
Investigations
Alanine Aminotransferase Increased	1/51 (2%)	1	3/50 (6%)	3	1/50 (2%)	1
Blood Glucose Increased	2/51 (3.9%)	2	1/50 (2%)	1	2/50 (4%)	2
Gamma-Glutamyltransferase Increased	2/51 (3.9%)	2	2/50 (4%)	2	0/50 (0%)	0
Nervous system disorders
Headache	4/51 (7.8%)	8	1/50 (2%)	1	2/50 (4%)	2
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	0/51 (0%)	0	0/50 (0%)	0	2/50 (4%)	2
Skin and subcutaneous tissue disorders
Pruritus	1/51 (2%)	1	2/50 (4%)	4	1/50 (2%)	1
Vascular disorders
Hypertension	2/51 (3.9%)	3	0/50 (0%)	0	1/50 (2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.