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This study has been terminated because of insufficient patient recruitment.
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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).
This study has been terminated because of insufficient patient recruitment. There were no safety concerns.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MT-9938 2.5μg | Active Comparator |
| |
| MT-9938 5μg | Active Comparator |
| |
| MT-9938 10μg | Active Comparator |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nalfurafine hydrochloride(MT-9938) 2.5μg | Drug | 2.5 μg (2capsules) once daily for 8 weeks |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 2 weeks, 4 weeks and 8 week |
| 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. | 2 weeks, 4 weeks and 8 weeks |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 8 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Los Angeles | California | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33283264 | Derived | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | MT-9938 2.5μg | Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks |
| FG001 | MT-9938 5μg | Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Nalfurafine hydrochloride(MT-9938) 5μg |
| Drug |
5 μg (2capsules) once daily for 8 weeks |
|
| Nalfurafine hydrochloride(MT-9938) 10μg | Drug | 10 μg (2capsules) once daily for 8 weeks |
|
| Placebo | Drug | Placebo (2capsules) once daily for 8 weeks |
|
| 2 weeks, 4 weeks and 8 weeks |
| 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. | 2 weeks, 4 weeks and 8 weeks |
| 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. | 2 weeks, 4 weeks and 8 weeks |
| 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. | 2 weeks, 4 weeks and 8 weeks |
| 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. | 2 weeks, 4 weeks and 8 weeks |
| 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. | 2 weeks, 4 weeks and 8 weeks |
| New York |
| New York |
| United States |
| Rosedale | New York | United States |
| San Antonio | Texas | United States |
| FG002 | MT-9938 10μg | Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks |
| FG003 | Placebo | Placebo: Placebo (2capsules) once daily for 8 weeks |
| COMPLETED |
|
| NOT COMPLETED |
|
|
ITT
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | MT-9938 2.5μg | Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks |
| BG001 | MT-9938 5μg | Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks |
| BG002 | MT-9938 10μg | Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks |
| BG003 | Placebo | Placebo: Placebo (2capsules) once daily for 8 weeks |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | ITT | Posted | Mean | Standard Deviation | score on a scale | 2 weeks, 4 weeks and 8 week |
|
|
| ||||||||||||||||||||||||||||||||||
| Primary | 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. | ITT | Posted | Mean | Standard Deviation | mm | 2 weeks, 4 weeks and 8 weeks |
| ||||||||||||||||||||||||||||||||||||
| Primary | 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. | ITT | Posted | Mean | Standard Deviation | score on a scale | 2 weeks, 4 weeks and 8 weeks |
| ||||||||||||||||||||||||||||||||||||
| Primary | 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. | ITT | Posted | Mean | Standard Deviation | score on a scale | 2 weeks, 4 weeks and 8 weeks |
| ||||||||||||||||||||||||||||||||||||
| Primary | 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. | ITT | Posted | Mean | Standard Deviation | score on a scale | 2 weeks, 4 weeks and 8 weeks |
| ||||||||||||||||||||||||||||||||||||
| Primary | 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. | ITT | Posted | Mean | Standard Deviation | units on a scale | 2 weeks, 4 weeks and 8 weeks |
| ||||||||||||||||||||||||||||||||||||
| Primary | 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. | ITT | Posted | Mean | Standard Deviation | score on a scale | 2 weeks, 4 weeks and 8 weeks |
| ||||||||||||||||||||||||||||||||||||
| Primary | 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. | 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. | Posted | Count of Participants | Participants | 2 weeks, 4 weeks and 8 weeks |
| |||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Count of Participants | Participants | 8 weeks |
|
|
8 weeks for treatment phase + 1 week follow-up visit after last dose
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MT-9938 2.5μg | Nalfurafine hydrochloride(MT-9938) 2.5μg: 2.5 μg (2capsules) once daily for 8 weeks | 0 | 10 | 4 | 10 | 2 | 10 |
| EG001 | MT-9938 5μg | Nalfurafine hydrochloride(MT-9938) 5μg: 5 μg (2capsules) once daily for 8 weeks | 0 | 13 | 0 | 13 | 2 | 13 |
| EG002 | MT-9938 10μg | Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks | 0 | 11 | 3 | 11 | 5 | 11 |
| EG003 | Placebo | Placebo: Placebo (2capsules) once daily for 8 weeks | 0 | 11 | 2 | 11 | 3 | 11 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 16.1 | Non-systematic Assessment |
| |
| Fluid Overload | Metabolism and nutrition disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Cardiac Failure Congestive | Cardiac disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Pancreatitis Relapsing | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 16.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperprolactinaemia | Endocrine disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 16.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 16.1 | Non-systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials Information Desk | Toray Industries, Inc | clinical-trials.toray.mb@mail.toray |
| ID | Term |
|---|---|
| D011537 | Pruritus |
| D012893 | Sleep Wake Disorders |
| ID | Term |
|---|---|
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
| D001523 | Mental Disorders |
Not provided
Not provided
| Male |
|
| At 4 weeks |
|
| At 8 weeks (EOT) |
|
| OG002 |
| MT-9938 10μg |
Nalfurafine hydrochloride(MT-9938) 10μg: 10 μg (2capsules) once daily for 8 weeks |
| OG003 | Placebo | Placebo: Placebo (2capsules) once daily for 8 weeks |
|
|
| Placebo |
Placebo: Placebo (2capsules) once daily for 8 weeks |
|
|
| Placebo |
Placebo: Placebo (2capsules) once daily for 8 weeks |
|
|
| OG003 | Placebo | Placebo: Placebo (2capsules) once daily for 8 weeks |
|
|
| OG003 | Placebo | Placebo: Placebo (2capsules) once daily for 8 weeks |
|
|
Placebo: Placebo (2capsules) once daily for 8 weeks
|
|
| OG003 | Placebo | Placebo: Placebo (2capsules) once daily for 8 weeks |
|
|
| Participants |
|
|
| Mild |
|
| Moderate |
|
| Severe |
|
| Missing |
|
| Title | Measurements |
|---|---|
| Excoriation not present |
|
| Mild |
|
| Moderate |
|
| Severe |
|
| Missing |
|
| Title | Measurements |
|---|---|
| Excoriation not present |
|
| Mild |
|
| Moderate |
|
| Severe |
|
| Missing |
|
| Title | Measurements |
|---|---|
| Excoriation not present |
|
| Mild |
|
| Moderate |
|
| Severe |
|
| Missing |
|