Clinical trial NCT02696499: Treatment of Uremic Pruritus With PA101B
Official title: Treatment of Uremic Pruritus With Inhaled PA101B in Patients With End-Stage Renal Disease Requiring Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Uremic Pruritus
Keywords: Uremic pruritus
Pruritus
Chronic itch
Itch
Hemodialysis
End-stage renal disease
Lead sponsor: Patara Pharma
Sponsor class: INDUSTRY
First posted: 2016-03-02
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Itching intensity
timeFrame: 7 weeks
Secondary outcomes:
measure: Pruritus-specific quality of life (QoL)
timeFrame: 7 weeks
measure: Pruritus-specific sleep quality
timeFrame: 7 weeks
measure: Assessment of depression
timeFrame: 7 weeks
measure: Patient Global Impression of Change (PGIC)
timeFrame: 7 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Kidney Disease and Hypertension Center
state: Arizona
city: Pine Bluff
country: United States
facility: US Renal Care
state: Arkansas
city: Northridge
country: United States
facility: Valley Renal Medical Group
state: California
city: San Dimas
country: United States
facility: North America Research Institute
state: California
city: Pembroke Pines
country: United States
facility: Pines Clinical Research, Inc.
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Research
state: Florida
city: Meridian
country: United States
facility: Boise Kidney and Hypertension Institute
state: Idaho
city: Evergreen Park
country: United States
facility: Fresenius Medical Care of Evergreen Park
state: Illinois
city: Albuquerque
country: United States
facility: Renal Medicine Associates
state: New Mexico
city: Gallup
country: United States
facility: US Renal Care
state: New Mexico
city: Ridgewood
country: United States
facility: Ridgewood Dialysis Center
state: New York
city: Winston-Salem
country: United States
facility: Brookview Hills Research Associates LLC
state: North Carolina
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
Study officials:
References:
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.