Efficacy and Safety of MT-9938 for Treatment of Uremic Pruritus in Subjects With End-stage Renal Disease Receiving Hemodialysis

• Sponsor: Toray Industries, Inc (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01660243
• Collaborator: (none)
• Enrollment: 45
• Locations: 4
• Arms: 4
• Duration (Months): 17.9
• Patients Per Site: 11.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study is being conducted to investigate the efficacy of MT-9938 compared with placebo after 2 weeks, to continue to evaluate efficacy for an additional 6 weeks, and to explore the effect of a reduction in itching intensity on health-related Quality of Life(QoL) domains, especially those which recent research suggests have a positive correlation with overall survival for this patient group. The study will consist of the following phases: Screening (1 to 2 weeks), Run in (1 week), double-blind Treatment (8 weeks), Washout (1 week) culminating in a Follow-up Visit (1 week after the last dose).

Condition or Disease	Intervention/Treatment	Phase
Uremic Pruritus	Drug: Nalfurafine hydrochloride(MT-9938) 2.5μg; Drug: Nalfurafine hydrochloride(MT-9938) 5μg; Drug: Nalfurafine hydrochloride(MT-9938) 10μg; Drug: Placebo	Phase 2

Detailed Description

This study has been terminated because of insufficient patient recruitment. There were no safety concerns.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-blind, Placebo-controlled, Fixed-dose, Parallel-group, Multicenter, Efficacy, and Safety Study of MT-9938 for Treatment of Uremic Pruritus in Subjects With End-stage Renal Disease Receiving Hemodialysis
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: MT-9938 2.5μg	Drug: Nalfurafine hydrochloride(MT-9938) 2.5μg; 2.5 μg (2capsules) once daily for 8 weeks
Active Comparator: MT-9938 5μg	Drug: Nalfurafine hydrochloride(MT-9938) 5μg; 5 μg (2capsules) once daily for 8 weeks
Active Comparator: MT-9938 10μg	Drug: Nalfurafine hydrochloride(MT-9938) 10μg; 10 μg (2capsules) once daily for 8 weeks
Placebo Comparator: Placebo	Drug: Placebo; Placebo (2capsules) once daily for 8 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Worst-itching 11-point Numerical Rating Scale (NRS) [2 weeks, 4 weeks and 8 week]

   The subject indicated the number on the line from left (0:no itching) to right (10:worst itch I have ever experienced). Assessments was made twice daily using an electronic Patient Reported Outcomes (ePRO) device from the Screening Visit to the Follow-up Visit (Week 9). The 2 daily assessments was separated by 12 h, at approximately 8 am and at approximately 8 pm. Subjects selected the number that best described the worst itch during the day (assessed at approximately 8 pm) or during the night (assessed at approximately 8 am). The day or night score, whichever was greater, was used to calculate the weekly average score and changes from baseline (average over the Run-in Phase [Days -7 to -1]) score in weekly average at 2, 4 and 8 weeks as specified in the protocol are reported. Amount of change score of plus indicates worsening, and minus indicates improvement.

2. Change From Baseline in Worst-itching Visual Analog Scale (VAS) [2 weeks, 4 weeks and 8 weeks]

   The subject placed a single vertical mark on the line of a VAS corresponding to degree of itching intensity from left (no itching) to right (worst itch I have ever experienced). The VAS represents a 100 mm line. It consists of 101 selectable regions and the subject's score on the VAS will correspond to the region (0 to 100) selected on the line. Assessments was made twice daily using an ePRO device from the Screening Visit to the Follow-up Visit (Week 9). The 2 daily assessments was separated by 12 h, in the morning at approximately 8 am and in the night at approximately 8 pm. Subjects put a single vertical mark on the line to show the intensity of your worst itching during the day or during the night. The day or night score, whichever was greater, was used to calculate the weekly average score and changes from baseline in weekly average at 2, 4 and 8 weeks as specified in the protocol are reported. Amount of change score of plus indicates worsening, and minus indicates improvement.

3. Change From Baseline in Itch Severity Score [2 weeks, 4 weeks and 8 weeks]

   The subject performed an assessment on day and nighttime symptoms of itch and effect of itch on sleep using a 5-point ordinal scale of itchiness (0 = none, 1 = mild, 2 = Moderate, 3=Severe, 4 = very severe). Assessments was made during each dialysis treatment (3x/week) and recorded on paper from the Screening Visit to the Follow-up Visit (Week 9). Change from Baseline (average over the Run-in Phase [Days -7 to -1]) in Weekly Averages of Itch Severity Score were assessed and score at 2, 4 and 8 weeks as specified in the protocol are reported. Amount of change score of plus indicates worsening, and minus indicates improvement.

4. Change From Baseline in Sleep Quality Assessment [2 weeks, 4 weeks and 8 weeks]

   The PSQI has a minimum possible score of 0 (better sleep quality) and a maximum possible score of 10 (worse sleep quality). Subjects was asked to rate their sleep experience during the previous week. Pittsburgh Sleep Quality Index (PSQI) modified assessment was made during the dialysis treatment 1x/week every week and recorded on paper from the Screening Visit to the Follow-up Visit (Week 9).Change from Baseline (the Run-in Phase [Days -7 to -1]) were assessed and score at 2, 4 and 8 weeks as specified in the protocol are reported. Amount of change score of plus indicates worsening, and minus indicates improvement.

5. Change From Baseline in QoL Assessment (Skindex-10) [2 weeks, 4 weeks and 8 weeks]

   The Skindex-10 has a minimum possible score of 0 (itching not bothersome) and a maximum possible score of 60 (itching very bothersome). The Skindex-10 is a self-administered questionnaire used to evaluate the health-related QoL in UP. It is comprised of 10 questions, adopted for pruritus from the Skindex-16, a widely used instrument for a variety of skin disease. Subjects was asked to identify on paper at Baseline and Weeks 2, 4, and 8 (EOT) what has bothered them most during the past week by marking along a scale 0 to 6 boxes from "never bothered" to "always bothered. Change from Baseline (the Run-in Phase [Days -7 to -1]) were assessed. Amount of change score of plus indicates worsening, and minus indicates improvement.

6. The Mean Value in Treatment Satisfaction (Patient's Global Impression of Change ) [2 weeks, 4 weeks and 8 weeks]

   The PGIC has a minimum possible score of 1 (very much improved) and a maximum possible score of 7 (very much worse). Subjects was asked to use a categorical scale with 7 categories to describe their global impression of change (PGIC) with study drug treatment. Subjects recorded their impression of change on paper at Weeks 2, 4, and 8 (EOT). Although the change from baseline (run-in phase [Days -7 to -1]) was specified as an outcome in this study, it was not calculated because the target enrollment was not met and no meaningful statistical analysis could be expected. Therefore, the mean value of patients at each point is shown instead.

7. Change From Baseline in QoL Assessment (5-D-Itch Scale) [2 weeks, 4 weeks and 8 weeks]

   The 5-D-Itch scale has a minimum possible score of 5 (better) and a maximum possible score of 25 (worse). Subjects was asked to assess QoL by means of the 5D-Itch-Scale at Baseline, Weeks 2, 4, and 8 (EOT). The 5D-Itch Scale is a 5-item (duration, degree, direction, disability, and distribution) multidimensional measure of pruritus itch. Change from Baseline (the Run-in Phase [Days -7 to -1]) were assessed. Amount of change score of plus indicates worsening, and minus indicates improvement.

8. The Number of Patients in Excoriation [2 weeks, 4 weeks and 8 weeks]

   Investigator and/or the designated medically qualified staff assessed the subject's excoriation at Baseline, and weekly thereafter, by completing the subject's answers to the following questions: Excoriation present? Yes/No If yes, please rate the severity: Mild/Moderate/Severe Although the change from baseline (run-in phase [Days -7 to -1]) was specified as an outcome in this study, it was not calculated because the target enrollment was not met and no meaningful statistical analysis could be expected. Therefore, the number of patients at each point is shown instead.

Secondary Outcome Measures

1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [8 weeks]

   The number of subjects with at least 1 treatment-emergent adverse event (TEAE). Please see the adverse event table for specific.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• On stable hemodialysis for at least 3 months

• Has stable functioning arteriovenous fistula, graft or other venous access

• Has continued (uncontrolled) uremic pruritus despite standard of care in the institution

• Has severe pruritus, as determined by a qualifying score of ≥3 on the Itch Severity Score Scale (0 to 4) either day or night during the week prior to Screening Visit

• Has no known drug addiction to any prescription, nonprescription, herbal or natural drugs, and successfully passes a drug screen test

• Women and men whose partners are of childbearing potential agree to practice the medically acceptable methods of birth control and agree to continue with the regimen throughout the duration of the study

• Capable of understanding and responding to the subject questionnaires, understands the purpose and risks of the study, and has given written informed consent

• Has rated his/her NRS score each day for at least 5 days out of the 7 days of the Run-in Phase

• Has severe pruritus, as determined by qualifying mean worst NRS score in a day of ≥5 (on 11 point NRS) at the end of the 1-week Run-in Phase

Exclusion Criteria:

• Current, clinically significant medical comorbidities

• Abnormal liver dysfunction

• Pruritus attributed mainly to any disease unrelated to kidney disease

• Calcium x phosphorus product >80 mg2/dL2 or hemoglobin <7 g/dL or parathyroid hormone levels >1000 pg/mL at Screening

• Received ultraviolet B treatment within 30 days prior to Screening

• Started or changed psychotropic medication within 14 days prior to Screening

• Is receiving opioid antagonists or opioid agonists within 7 days prior to Screening and not willing to abstain from these medications during the study.

• Started or changed medications, creams or emollients including over-the-counter oil bath treatment for relief of pruritus within 7 days prior to Screening

• Has known hypersensitivity to opioids or the study drug ingredients

• Is currently participating in an investigational drug or device clinical study or was participating in such a study within 30 days prior to the start of Screening

• Female subject who is known to be pregnant or nursing

• Is considered not suitable for inclusion in the study in the opinion of Investigator

• Has current suicidal ideation with some intent to act or with specific plan and intent or had suicidal behavior at any time in subject's life

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States
2		New York	New York	United States
3		Rosedale	New York	United States
4		San Antonio	Texas	United States

Sponsors and Collaborators

• Toray Industries, Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Toray Industries, Inc
• ClinicalTrials.gov Identifier: NCT01660243
• Other Study ID Numbers: MT-9938-A01
• First Posted: Aug 8, 2012
• Last Update Posted: Feb 9, 2022
• Last Verified: Nov 1, 2021

• Keywords provided by Toray Industries, Inc: Pruritus; Renal dialysis; Receptors, Opioid, kappa; Sleep Disorders; Quality of Life
• Additional relevant MeSH terms: Kidney Failure, Chronic; Pruritus

Study Results

Participant Flow

Pre-assignment Detail

Subjects who remained eligible entered the 1-week Run-in Phase. The NRS, VAS, and Itch Severity Score were averaged and formed the Baseline itch-intensity scores. After the Run-in, subjects who met additional inclusion criteria (having an NRS score for at least 5 days out of the 7 days and a mean worst NRS score ≥5) entered the Double-blind Treatment Phase (8 weeks) and were randomized to 1 of 4 study treatments.

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks
Period Title: Overall Study
STARTED	10	13	11	11
COMPLETED	8	13	9	10
NOT COMPLETED	2	0	2	1

Baseline Characteristics

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo	Total
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks	Total of all reporting groups
Overall Participants	10	13	11	11	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.5 (10.62)	54.6 (12.78)	55.3 (13.64)	55.2 (12.94)	55.8 (12.25)
Sex: Female, Male (Count of Participants)
Female	5 50%	2 15.4%	2 18.2%	4 36.4%	13 28.9%
Male	5 50%	11 84.6%	9 81.8%	7 63.6%	32 71.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Worst-itching 11-point Numerical Rating Scale (NRS)
Description	The subject indicated the number on the line from left (0:no itching) to right (10:worst itch I have ever experienced). Assessments was made twice daily using an electronic Patient Reported Outcomes (ePRO) device from the Screening Visit to the Follow-up Visit (Week 9). The 2 daily assessments was separated by 12 h, at approximately 8 am and at approximately 8 pm. Subjects selected the number that best described the worst itch during the day (assessed at approximately 8 pm) or during the night (assessed at approximately 8 am). The day or night score, whichever was greater, was used to calculate the weekly average score and changes from baseline (average over the Run-in Phase [Days -7 to -1]) score in weekly average at 2, 4 and 8 weeks as specified in the protocol are reported. Amount of change score of plus indicates worsening, and minus indicates improvement.
Time Frame	2 weeks, 4 weeks and 8 week

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks
Measure Participants	10	13	11	11
At 2 weeks	-1.11 (1.224)	-1.19 (1.177)	-1.12 (0.828)	-2.27 (2.774)
At 4 weeks	-1.41 (2.032)	-2.12 (2.527)	-1.85 (1.392)	-2.25 (3.114)
At 8 weeks (EOT)	-2.33 (2.269)	-3.13 (2.833)	-3.42 (2.262)	-3.39 (3.614)

2. Primary Outcome

Title	Change From Baseline in Worst-itching Visual Analog Scale (VAS)
Description	The subject placed a single vertical mark on the line of a VAS corresponding to degree of itching intensity from left (no itching) to right (worst itch I have ever experienced). The VAS represents a 100 mm line. It consists of 101 selectable regions and the subject's score on the VAS will correspond to the region (0 to 100) selected on the line. Assessments was made twice daily using an ePRO device from the Screening Visit to the Follow-up Visit (Week 9). The 2 daily assessments was separated by 12 h, in the morning at approximately 8 am and in the night at approximately 8 pm. Subjects put a single vertical mark on the line to show the intensity of your worst itching during the day or during the night. The day or night score, whichever was greater, was used to calculate the weekly average score and changes from baseline in weekly average at 2, 4 and 8 weeks as specified in the protocol are reported. Amount of change score of plus indicates worsening, and minus indicates improvement.
Time Frame	2 weeks, 4 weeks and 8 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks
Measure Participants	10	13	11	11
At 2 weeks	-8.77 (15.158)	-12.27 (12.154)	-6.56 (18.778)	-21.09 (26.719)
At 4 weeks	-14.17 (22.631)	-19.46 (25.097)	-21.24 (20.300)	-23.63 (31.239)
At 8 weeks (EOT)	-23.06 (23.686)	-29.16 (27.628)	-24.49 (42.732)	-30.09 (31.582)

3. Primary Outcome

Title	Change From Baseline in Itch Severity Score
Description	The subject performed an assessment on day and nighttime symptoms of itch and effect of itch on sleep using a 5-point ordinal scale of itchiness (0 = none, 1 = mild, 2 = Moderate, 3=Severe, 4 = very severe). Assessments was made during each dialysis treatment (3x/week) and recorded on paper from the Screening Visit to the Follow-up Visit (Week 9). Change from Baseline (average over the Run-in Phase [Days -7 to -1]) in Weekly Averages of Itch Severity Score were assessed and score at 2, 4 and 8 weeks as specified in the protocol are reported. Amount of change score of plus indicates worsening, and minus indicates improvement.
Time Frame	2 weeks, 4 weeks and 8 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks
Measure Participants	10	13	11	11
At 2 weeks	-0.77 (0.721)	-0.77 (0.542)	-0.43 (0.872)	-0.92 (1.106)
At 4 weeks	-0.81 (0.835)	-1.08 (0.741)	-1.30 (0.885)	-0.90 (1.275)
At 8 weeks (EOT)	-1.13 (1.003)	-1.49 (0.919)	-1.28 (1.094)	-1.28 (1.197)

4. Primary Outcome

Title	Change From Baseline in Sleep Quality Assessment
Description	The PSQI has a minimum possible score of 0 (better sleep quality) and a maximum possible score of 10 (worse sleep quality). Subjects was asked to rate their sleep experience during the previous week. Pittsburgh Sleep Quality Index (PSQI) modified assessment was made during the dialysis treatment 1x/week every week and recorded on paper from the Screening Visit to the Follow-up Visit (Week 9).Change from Baseline (the Run-in Phase [Days -7 to -1]) were assessed and score at 2, 4 and 8 weeks as specified in the protocol are reported. Amount of change score of plus indicates worsening, and minus indicates improvement.
Time Frame	2 weeks, 4 weeks and 8 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks
Measure Participants	10	13	11	11
At 2 weeks	-0.4 (1.06)	-0.2 (2.17)	-0.2 (1.64)	-1.0 (1.15)
At 4 weeks	-0.4 (1.92)	-0.3 (1.65)	-1.1 (1.36)	-0.1 (1.36)
At 8 weeks (EOT)	-1.1 (1.35)	-0.6 (1.62)	-1.2 (1.55)	-0.4 (1.59)

5. Primary Outcome

Title	Change From Baseline in QoL Assessment (Skindex-10)
Description	The Skindex-10 has a minimum possible score of 0 (itching not bothersome) and a maximum possible score of 60 (itching very bothersome). The Skindex-10 is a self-administered questionnaire used to evaluate the health-related QoL in UP. It is comprised of 10 questions, adopted for pruritus from the Skindex-16, a widely used instrument for a variety of skin disease. Subjects was asked to identify on paper at Baseline and Weeks 2, 4, and 8 (EOT) what has bothered them most during the past week by marking along a scale 0 to 6 boxes from "never bothered" to "always bothered. Change from Baseline (the Run-in Phase [Days -7 to -1]) were assessed. Amount of change score of plus indicates worsening, and minus indicates improvement.
Time Frame	2 weeks, 4 weeks and 8 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks
Measure Participants	10	13	11	11
At 2 weeks	-5.5 (8.55)	-11.6 (11.16)	-5.4 (9.27)	-13.6 (15.21)
At 4 weeks	-0.5 (14.99)	-16.5 (15.00)	-16.4 (14.55)	-13.7 (17.68)
At 8 weeks (EOT)	-11.9 (5.61)	-23.5 (15.52)	-19.2 (14.59)	-16.3 (14.63)

6. Primary Outcome

Title	The Mean Value in Treatment Satisfaction (Patient's Global Impression of Change )
Description	The PGIC has a minimum possible score of 1 (very much improved) and a maximum possible score of 7 (very much worse). Subjects was asked to use a categorical scale with 7 categories to describe their global impression of change (PGIC) with study drug treatment. Subjects recorded their impression of change on paper at Weeks 2, 4, and 8 (EOT). Although the change from baseline (run-in phase [Days -7 to -1]) was specified as an outcome in this study, it was not calculated because the target enrollment was not met and no meaningful statistical analysis could be expected. Therefore, the mean value of patients at each point is shown instead.
Time Frame	2 weeks, 4 weeks and 8 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks
Measure Participants	10	13	11	11
2 weeks	3.1 (0.64)	3.1 (1.51)	3.0 (0.87)	2.6 (1.07)
4 weeks	3.3 (0.71)	2.8 (1.36)	2.5 (0.93)	2.8 (1.09)
8 weeks	2.6 (0.98)	1.9 (0.90)	2.1 (1.17)	2.2 (1.30)

7. Primary Outcome

Title	Change From Baseline in QoL Assessment (5-D-Itch Scale)
Description	The 5-D-Itch scale has a minimum possible score of 5 (better) and a maximum possible score of 25 (worse). Subjects was asked to assess QoL by means of the 5D-Itch-Scale at Baseline, Weeks 2, 4, and 8 (EOT). The 5D-Itch Scale is a 5-item (duration, degree, direction, disability, and distribution) multidimensional measure of pruritus itch. Change from Baseline (the Run-in Phase [Days -7 to -1]) were assessed. Amount of change score of plus indicates worsening, and minus indicates improvement.
Time Frame	2 weeks, 4 weeks and 8 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks
Measure Participants	10	13	11	11
At 2 weeks	-2.8 (2.12)	-3.3 (2.46)	-3.0 (2.62)	-6.1 (5.84)
At 4 weeks	-1.6 (4.17)	-5.1 (3.80)	-5.6 (3.16)	-5.7 (5.02)
At 8 weeks	-3.7 (3.90)	-8.6 (4.25)	-6.2 (5.01)	-7.6 (4.53)

8. Primary Outcome

Title	The Number of Patients in Excoriation
Description	Investigator and/or the designated medically qualified staff assessed the subject's excoriation at Baseline, and weekly thereafter, by completing the subject's answers to the following questions: Excoriation present? Yes/No If yes, please rate the severity: Mild/Moderate/Severe Although the change from baseline (run-in phase [Days -7 to -1]) was specified as an outcome in this study, it was not calculated because the target enrollment was not met and no meaningful statistical analysis could be expected. Therefore, the number of patients at each point is shown instead.
Time Frame	2 weeks, 4 weeks and 8 weeks

Outcome Measure Data

Analysis Population Description

Not all rows could be analyzed with the overall number analyzed due to several reasons (e.g. patient discontinuation, missing data etc.), so some rows have different number of subjects analyzed.

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks
Measure Participants	10	13	11	11
Excoriation not present	7 70%	6 46.2%	7 63.6%	7 63.6%
Mild	2 20%	4 30.8%	3 27.3%	2 18.2%
Moderate	1 10%	2 15.4%	1 9.1%	2 18.2%
Severe	0 0%	0 0%	0 0%	0 0%
Missing	0 0%	0 0%	0 0%	0 0%
Excoriation not present	6 60%	7 53.8%	7 63.6%	7 63.6%
Mild	2 20%	5 38.5%	2 18.2%	3 27.3%
Moderate	0 0%	0 0%	0 0%	0 0%
Severe	0 0%	0 0%	0 0%	0 0%
Missing	0 0%	0 0%	0 0%	0 0%
Excoriation not present	6 60%	11 84.6%	7 63.6%	7 63.6%
Mild	2 20%	2 15.4%	1 9.1%	2 18.2%
Moderate	0 0%	0 0%	0 0%	1 9.1%
Severe	0 0%	0 0%	0 0%	0 0%
Missing	0 0%	0 0%	0 0%	0 0%
Excoriation not present	6 60%	9 69.2%	9 81.8%	7 63.6%
Mild	1 10%	2 15.4%	0 0%	1 9.1%
Moderate	0 0%	1 7.7%	0 0%	0 0%
Severe	0 0%	0 0%	0 0%	1 9.1%
Missing	0 0%	0 0%	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Description	The number of subjects with at least 1 treatment-emergent adverse event (TEAE). Please see the adverse event table for specific.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MT-9938 2.5μg	MT-9938 5μg	MT-9938 10μg	Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks	Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks	Placebo: Placebo (2capsules) once daily for 8 weeks
Measure Participants	10	13	11	11
Count of Participants [Participants]	6 60%	5 38.5%	9 81.8%	6 54.5%

Adverse Events

Time Frame	8 weeks for treatment phase + 1 week follow-up visit after last dose
Arm/Group Title	MT-9938 2.5μg		MT-9938 5μg		MT-9938 10μg		Placebo
Arm/Group Description	Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks		Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks		Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks		Placebo: Placebo (2capsules) once daily for 8 weeks
All Cause Mortality
	MT-9938 2.5μg		MT-9938 5μg		MT-9938 10μg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/13 (0%)		0/11 (0%)		0/11 (0%)
Serious Adverse Events
	MT-9938 2.5μg		MT-9938 5μg		MT-9938 10μg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		0/13 (0%)		3/11 (27.3%)		2/11 (18.2%)
Cardiac disorders
Cardiac Failure Congestive	0/10 (0%)		0/13 (0%)		2/11 (18.2%)		0/11 (0%)
Gastrointestinal disorders
Pancreatitis Relapsing	1/10 (10%)		0/13 (0%)		0/11 (0%)		0/11 (0%)
General disorders
Asthenia	0/10 (0%)		0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Infections and infestations
Cellulitis	0/10 (0%)		0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Diverticulitis	1/10 (10%)		0/13 (0%)		0/11 (0%)		0/11 (0%)
Pneumonia	0/10 (0%)		0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Metabolism and nutrition disorders
Fluid Overload	1/10 (10%)		0/13 (0%)		0/11 (0%)		0/11 (0%)
Hypercalcaemia	1/10 (10%)		0/13 (0%)		0/11 (0%)		0/11 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/10 (0%)		0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Pleural Effusion	0/10 (0%)		0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	MT-9938 2.5μg		MT-9938 5μg		MT-9938 10μg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20%)		2/13 (15.4%)		5/11 (45.5%)		3/11 (27.3%)
Endocrine disorders
Hyperprolactinaemia	1/10 (10%)		1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Nausea	1/10 (10%)		0/13 (0%)		3/11 (27.3%)		1/11 (9.1%)
Psychiatric disorders
Insomnia	1/10 (10%)		1/13 (7.7%)		5/11 (45.5%)		1/11 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The disclosure restriction on the PIs is that 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 from the time submitted to sponsor for review. Sponsor can require changes to the communication which is considered confidential and/or proprietary. If necessary, sponsor shall have the right to request to delay the proposed disclosure for an additional 60 days.