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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Mitsubishi Tanabe Pharma Corporation
ClinicalTrials.gov Identifier:
NCT01660243
First received: August 2, 2012
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Uremic Pruritus
Drug: Nalfurafine hydrochloride 2.5μg
Drug: Nalfurafine hydrochloride 5μg
Drug: Nalfurafine hydrochloride 10μg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Mitsubishi Tanabe Pharma Corporation:

Primary Outcome Measures:
  • Change from baseline in Worst-itching 11-point Numerical Rating Scale (NRS) [ Time Frame: 2 weeks, 4 weeks and 8 week ] [ Designated as safety issue: No ]
  • Change from baseline in Worst-itching Visual Analog Scale (VAS) [ Time Frame: 2 weeks, 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Itch Severity Score [ Time Frame: 2 weeks, 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Sleep quality assessment [ Time Frame: 2 weeks, 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Excoriation [ Time Frame: 2 weeks, 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in QoL assessment [ Time Frame: 2 weeks, 4 weeks and 8 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Treatment satisfaction (Patient's Global Impression of Change ) [ Time Frame: 2 weeks, 4 weeks and 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 360
Study Start Date: September 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MT-9938 2.5μg Drug: Nalfurafine hydrochloride 2.5μg
2.5 μg (2capsules) once daily for 8 weeks
Active Comparator: MT-9938 5μg Drug: Nalfurafine hydrochloride 5μg
5 μg (2capsules) once daily for 8 weeks
Active Comparator: MT-9938 10μg Drug: Nalfurafine hydrochloride 10μg
10 μg (2capsules) once daily for 8 weeks
Placebo Comparator: Placebo Drug: Placebo
Placebo (2capsules) once daily for 8 weeks

Detailed Description:

MT-9938 is a potent and selective agonist for the kappa -opioid receptor and a novel derivative of the opioid receptor antagonist, naltrexone. Although MT-9938 is not designated a Schedule-controlled substance in Japan and Europe, MT-9938 is currently a Schedule II substance under the Controlled Substance Act in the United States as a derivative of noroxymorphone based on the chemical structure. DOPPS has reported 70% of patients having some degree of pruritus, with 42-45% moderately-to-extremely being bothered by itchiness. For this subset of hemodialysis patients, the intensity of pruritus is highly correlated with multiple measures of QoL.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01660243

Locations
United States, California
Los Angeles, California, United States
United States, New York
New York, New York, United States
Rosedale, New York, United States
United States, Texas
San Antonio, Texas, United States
Sponsors and Collaborators
Mitsubishi Tanabe Pharma Corporation
  More Information

No publications provided

Responsible Party: Mitsubishi Tanabe Pharma Corporation
ClinicalTrials.gov Identifier: NCT01660243     History of Changes
Other Study ID Numbers: MT-9938-A01
Study First Received: August 2, 2012
Last Updated: March 4, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Mitsubishi Tanabe Pharma Corporation:
Pruritus
Renal dialysis
Receptors, Opioid, kappa
Sleep Disorders
Quality of Life

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Pruritus
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Skin Diseases
Skin Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on April 16, 2014