Treatment of Uremic Pruritus With PA101B

Treatment of Uremic Pruritus With Inhaled PA101B in Patients With End-Stage Renal Disease Requiring Hemodialysis

This is a randomized, double blind, placebo-controlled, parallel-arm, multi-center, Phase 2, proof-of-concept efficacy and safety study in patients with end-stage renal disease requiring hemodialysis.

The purpose of the study is to determine the efficacy and safety profile of PA101B delivered via eFlow high efficiency nebulizer in patients with uremic pruritus who are symptomatic despite using standard treatments.

Study Overview

• Status: Completed
• Conditions: Uremic Pruritus
• Intervention / Treatment: Drug: PA101B; Drug: Placebo

Detailed Description

The symptom score for determining eligibility will be established during the Screening Period (up to 4 weeks) and eligible patients will be randomly allocated in a 2:1 ratio between the active and placebo arms at the baseline visit (Week 0). During the Treatment Period, clinic visits will occur at the end of Weeks 1, 3, 5 and 7. Following completion of the Treatment Period, patients will enter a 2-week Washout Period in both treatment arms.

Routine hemodialysis treatment will continue according to the dialysis unit's standard practice in all patients.

Patients will be allowed to continue to use the same daily doses of pre-randomization H1 antihistamines as well as the same daily doses of any other allowed medications throughout the study.

Blood samples will be collected for various biomarkers. In a subset of patients, additional blood samples will be collected for pharmacokinetic assessments. Clinical safety assessments will be performed at each clinic visit.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Kidney Disease and Hypertension Center
  • Arkansas
    • Pine Bluff, Arkansas, United States, 71603
      • US Renal Care
  • California
    • Northridge, California, United States, 91324
      • Valley Renal Medical Group
    • San Dimas, California, United States, 91773
      • North America Research Institute
  • Florida
    • Pembroke Pines, Florida, United States, 33028
      • Pines Clinical Research, Inc.
    • Tampa, Florida, United States, 33614
      • Genesis Clinical Research
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Boise Kidney and Hypertension Institute
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
      • Fresenius Medical Care of Evergreen Park
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Renal Medicine Associates
    • Gallup, New Mexico, United States, 87313
      • US Renal Care
  • New York
    • Ridgewood, New York, United States, 11385
      • Ridgewood Dialysis Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Brookview Hills Research Associates LLC
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
      • Southeast Renal Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of end-stage renal disease (ESRD) requiring hemodialysis for at least 3 months prior to the Screening Period
• Receiving conventional hemodialysis (i.e., not hemofiltration or hemodiafiltration)
• Pruritus present for at least 6 weeks of Screening
• Mean pruritus severity score on a numerical rating scale (NRS) > 4
• Patient-Assessed Disease Severity Scale Type B or C at Screening
• Documentation of a urea reduction ratio (URR) >65% or single-pooled Kt/V> 1.4 during Screening
• Willing and able to provide written informed consent

Exclusion Criteria:

• Current or recent history of clinically significant medical condition, laboratory abnormality, or illness that could put the patient at risk or compromise the quality of the study data as determined by the investigator
• Myocardial infarction within 6 months or unstable angina, acute coronary syndrome, or interventional coronary procedure within 2 months of Screening
• Upper or lower respiratory tract infection (including sinus infection) within 4 weeks of Screening
• Severely symptomatic cardiopulmonary disease defined by the use of home oxygen treatment, dyspnea at rest or with minimal exertion, uncontrolled arrhythmias (e.g. atrial fibrillation with inadequate rate control), or history of life-threatening arrhythmias (e.g. cardiac arrest or syncope related to arrhythmia)
• Acute exacerbation of asthma or chronic obstructive pulmonary disease resulting in hospitalization or visit to an emergency department or urgent care clinic within 6 months of Screening
• Hospitalization for any medical reason other than for a pre-planned procedure or dialysis access related procedure within the 2 weeks of Screening
• Malignancy requiring active treatment with a systemic drug
• Participation in any other investigation drug study within 4 weeks of Screening
• Current or anticipated use of baclofen, gabapentin, pregabalin and nalbuphine for the treatment of pruritus
• Current or anticipated use of glucocorticoids administered intravenously, orally, or transdermally
• Pregnant or breastfeeding females, or if of child-bearing potential unwilling to practice acceptable means of birth control or abstinence during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo administered via inhalation twice daily for 7 weeks
Experimental: PA101B	Drug: PA101B; 40 mg PA101B administered via inhalation twice daily for 7 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Itching intensity	Numerical rating scale (NRS)	7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pruritus-specific quality of life (QoL)	Skindex-10	7 weeks
Pruritus-specific sleep quality	Itch MOS	7 weeks
Assessment of depression	Beck Depression Inventory-II	7 weeks
Patient Global Impression of Change (PGIC)		7 weeks

Collaborators and Investigators

• Sponsor: Patara Pharma

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: February 25, 2016
• First Submitted That Met QC Criteria: February 25, 2016
• First Posted (Estimate): March 2, 2016

Study Record Updates

• Last Update Posted (Actual): April 20, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: End-stage renal disease; Itch; Hemodialysis; Pruritus; Uremic pruritus; Chronic itch
• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus
• Other Study ID Numbers: PA101B-UP-02