Back to resultsEfficacy and Safety of MT-9938 for Treatment of Uremic Pruritus in Subjects With End-stage Renal Disease Receiving Hemodialysis
Primary Purpose
Uremic Pruritus
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nalfurafine hydrochloride(MT-9938) 2.5μg
Nalfurafine hydrochloride(MT-9938) 5μg
Nalfurafine hydrochloride(MT-9938) 10μg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Uremic Pruritus focused on measuring Pruritus, Renal dialysis, Receptors, Opioid, kappa, Sleep Disorders, Quality of Life
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
MT-9938 2.5μg
MT-9938 5μg
MT-9938 10μg
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Change From Baseline in Worst-itching 11-point Numerical Rating Scale (NRS)
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.
Change From Baseline in Worst-itching Visual Analog Scale (VAS)
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.
Change From Baseline in Itch Severity Score
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.
Change From Baseline in Sleep Quality Assessment
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.
Change From Baseline in QoL Assessment (Skindex-10)
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.
The Mean Value in Treatment Satisfaction (Patient's Global Impression of Change )
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.
Change From Baseline in QoL Assessment (5-D-Itch Scale)
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.
The Number of Patients in Excoriation
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
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
The number of subjects with at least 1 treatment-emergent adverse event (TEAE). Please see the adverse event table for specific.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01660243
Brief Title
Efficacy and Safety of MT-9938 for Treatment of Uremic Pruritus in Subjects With End-stage Renal Disease Receiving Hemodialysis
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 Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Terminated
Why Stopped
This study has been terminated because of insufficient patient recruitment.
Study Start Date
September 2012 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Toray Industries, Inc
4. Oversight
Data Monitoring Committee
No
5. 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).
Detailed Description
This study has been terminated because of insufficient patient recruitment. There were no safety concerns.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uremic Pruritus
Keywords
Pruritus, Renal dialysis, Receptors, Opioid, kappa, Sleep Disorders, Quality of Life
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MT-9938 2.5μg
Arm Type
Active Comparator
Arm Title
MT-9938 5μg
Arm Type
Active Comparator
Arm Title
MT-9938 10μg
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Nalfurafine hydrochloride(MT-9938) 2.5μg
Intervention Description
2.5 μg (2capsules) once daily for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Nalfurafine hydrochloride(MT-9938) 5μg
Intervention Description
5 μg (2capsules) once daily for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Nalfurafine hydrochloride(MT-9938) 10μg
Intervention Description
10 μg (2capsules) once daily for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo (2capsules) once daily for 8 weeks
Primary Outcome Measure Information:
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
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
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
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
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
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
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
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
Secondary Outcome Measure Information:
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
City
Los Angeles
State/Province
California
Country
United States
City
New York
State/Province
New York
Country
United States
City
Rosedale
State/Province
New York
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
33283264
Citation
Hercz D, Jiang SH, Webster AC. Interventions for itch in people with advanced chronic kidney disease. Cochrane Database Syst Rev. 2020 Dec 7;12(12):CD011393. doi: 10.1002/14651858.CD011393.pub2.
Results Reference
derived
Learn more about this trial
Efficacy and Safety of MT-9938 for Treatment of Uremic Pruritus in Subjects With End-stage Renal Disease Receiving Hemodialysis
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