Impact of renal impairment on the pharmacokinetic profile of intravenous difelikefalin, a kappa opioid receptor agonist for the treatment of pruritus.

Spencer RH, Noonan PK, Marbury T, Menzaghi F

BMC nephrology14 Oct 2024Cited by 3 (Europe PMC)

PMID39402448PMCIDPMC11476771DOI10.1186/s12882-024-03790-wPepBankPUB-39402448

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: CC BY-NC-ND. Results still quote short attributed sentences.

Results from this study10

10 results from studies that gave the peptide. 10 results from people.

01HumanNon-randomized trialPharmacokinetics
In non-dialysis-dependent subjects, difelikefalin clearance decreased as renal impairment increased.
In plain wordsDifelikefalin clearance decreased as kidney impairment increased.
Peptide
Difelikefalin
Outcome
DecreaseClearance by renal impairment
Study
n = 36
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
3.0 mcg/kg · intravenous · single doseAs given in this study (human).
Source sentences
Summary
Clearance of difelikefalin correspondingly decreased with increasing renal impairment.
2 context sentences(design, population, supporting numbers)
Summary · context
The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects.
Summary · context
Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).
Report a problemFND-3940244805
02HumanNon-randomized trialPharmacokinetics
In subjects with ESRD undergoing haemodialysis, difelikefalin demonstrated dose proportionality.
In plain wordsIn dialysis patients, difelikefalin exposure was proportional to dose.
Peptide
Difelikefalin
Outcome
Not applicableDose proportionality in ESRD
Study
n = 19
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
0.5, 1.0, or 2.5 mcg/kg · intravenous · 3 doses over 1 weekAs given in this study (human).
Source sentences
Summary
In the multiple-dose study in subjects with ESRD undergoing HD (N = 19), IV difelikefalin demonstrated dose proportionality and was shown to be mostly cleared by dialysis; steady state was achieved with the second dose on day 3.
2 context sentences(design, population, supporting numbers)
Summary · context
The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects.
Summary · context
Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).
Report a problemFND-3940244806
03HumanNon-randomized trialPharmacokinetics
In subjects with ESRD, difelikefalin was mostly cleared by dialysis.
In plain wordsIn patients with kidney failure, dialysis removed most difelikefalin.
Peptide
Difelikefalin
Outcome
Not applicableDialysis clearance
Study
n = 19
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
0.5, 1.0, or 2.5 mcg/kg · intravenous · 3 doses over 1 weekAs given in this study (human).
Source sentences
Summary
In the multiple-dose study in subjects with ESRD undergoing HD (N = 19), IV difelikefalin demonstrated dose proportionality and was shown to be mostly cleared by dialysis; steady state was achieved with the second dose on day 3.
2 context sentences(design, population, supporting numbers)
Summary · context
The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects.
Summary · context
Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).
Report a problemFND-3940244807
04HumanNon-randomized trialPharmacokinetics
In subjects with ESRD undergoing haemodialysis, difelikefalin reached steady state with the second dose on day 3.
In plain wordsIn dialysis patients, difelikefalin reached steady levels with the second dose on day 3.
Peptide
Difelikefalin
Outcome
Not applicableTime to steady state
Study
n = 19
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
0.5, 1.0, or 2.5 mcg/kg · intravenous · 3 doses over 1 weekAs given in this study (human).
Source sentences
Summary
In the multiple-dose study in subjects with ESRD undergoing HD (N = 19), IV difelikefalin demonstrated dose proportionality and was shown to be mostly cleared by dialysis; steady state was achieved with the second dose on day 3.
2 context sentences(design, population, supporting numbers)
Summary · context
The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects.
Summary · context
Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).
Report a problemFND-3940244808
05HumanNon-randomized trialPharmacokinetics
After difelikefalin dosing, subjects with mild renal impairment had exposure comparable to healthy subjects.
In plain wordsDifelikefalin exposure was similar in people with mild kidney impairment and healthy people.
Peptide
Difelikefalin
Outcome
Not applicableExposure in mild renal impairment
Study
n: not reported in source
Comparator
Healthy subjects with normal renal function
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
3.0 mcg/kg · intravenous · single doseAs given in this study (human).
Source sentences
Summary
Single IV dosing of difelikefalin in NDD subjects (N = 36) with mild renal impairment demonstrated comparable exposure to healthy subjects with normal renal function, while subjects with moderate or severe renal impairment had higher total exposure.
2 context sentences(design, population, supporting numbers)
Summary · context
The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects.
Summary · context
Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).
Report a problemFND-3940244801
06HumanNon-randomized trialPharmacokinetics
After difelikefalin dosing, subjects with moderate renal impairment had higher total exposure than healthy subjects.
In plain wordsDifelikefalin exposure was higher in people with moderate kidney impairment than healthy people.
Peptide
Difelikefalin
Outcome
IncreaseExposure in moderate renal impairment
Study
n: not reported in source
Comparator
Healthy subjects with normal renal function
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
3.0 mcg/kg · intravenous · single doseAs given in this study (human).
Source sentences
Summary
Single IV dosing of difelikefalin in NDD subjects (N = 36) with mild renal impairment demonstrated comparable exposure to healthy subjects with normal renal function, while subjects with moderate or severe renal impairment had higher total exposure.
2 context sentences(design, population, supporting numbers)
Summary · context
The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects.
Summary · context
Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).
Report a problemFND-3940244802
07HumanNon-randomized trialPharmacokinetics
After difelikefalin dosing, subjects with severe renal impairment had higher total exposure than healthy subjects.
In plain wordsDifelikefalin exposure was higher in people with severe kidney impairment than healthy people.
Peptide
Difelikefalin
Outcome
IncreaseExposure in severe renal impairment versus healthy subjects
Study
n: not reported in source
Comparator
Healthy subjects with normal renal function
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
3.0 mcg/kg · intravenous · single doseAs given in this study (human).
Source sentences
Summary
Single IV dosing of difelikefalin in NDD subjects (N = 36) with mild renal impairment demonstrated comparable exposure to healthy subjects with normal renal function, while subjects with moderate or severe renal impairment had higher total exposure.
2 context sentences(design, population, supporting numbers)
Summary · context
The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects.
Summary · context
Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).
Report a problemFND-3940244803
08HumanNon-randomized trialPharmacokinetics
After difelikefalin dosing, subjects with severe renal impairment had higher total exposure than those with moderate impairment.
In plain wordsDifelikefalin exposure was higher with severe kidney impairment than moderate impairment.
Peptide
Difelikefalin
Outcome
IncreaseExposure in severe versus moderate renal impairment
Study
n: not reported in source
Comparator
Moderate renal impairment
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
3.0 mcg/kg · intravenous · single doseAs given in this study (human).
Source sentences
Summary
NDD subjects with severe renal impairment had higher total exposure compared with those with moderate renal impairment (i.e., exposure in severe NDD > moderate NDD > mild NDD ≈ healthy subjects).
2 context sentences(design, population, supporting numbers)
Summary · context
The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects.
Summary · context
Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).
Report a problemFND-3940244804
09HumanNon-randomized trialSafety outcome
In subjects across renal-function groups, safety findings matched the known intravenous difelikefalin profile.
In plain wordsSafety findings matched the known difelikefalin profile across the study groups.
Peptide
Difelikefalin
Outcome
Not applicableSafety profile
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated · intravenousAs given in this study (human).
Source sentences
Summary
Safety findings for all subjects were consistent with the known profile of IV difelikefalin.
2 context sentences(design, population, supporting numbers)
Summary · context
The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects.
Summary · context
Based on those data, the PK and safety of 3 dose levels of IV difelikefalin (0.5, 1.0, or 2.5 mcg/kg) were compared with matched placebo in subjects undergoing HD with each dose administered following dialysis, 3 times over a 1-week treatment period).
Report a problemFND-3940244809
10HumanNon-randomized trialPharmacokinetics
After difelikefalin dosing, subjects with moderate renal impairment had higher total exposure than those with mild impairment.
In plain wordsDifelikefalin exposure was higher with moderate kidney impairment than mild impairment.
Peptide
Difelikefalin
Outcome
IncreaseExposure in moderate versus mild renal impairment
Study
n: not reported in source
Comparator
Mild renal impairment
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
3.0 mcg/kg · intravenous · single doseAs given in this study (human).
Source sentences
Summary
NDD subjects with severe renal impairment had higher total exposure compared with those with moderate renal impairment (i.e., exposure in severe NDD > moderate NDD > mild NDD ≈ healthy subjects).
1 context sentence(design, population, supporting numbers)
Summary · context
The PK and safety of single IV doses of difelikefalin (3.0 mcg/kg) were initially evaluated in NDD subjects with mild, moderate, or severe renal impairment compared with matched healthy subjects.
Report a problemFND-3940244810

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2NCT02229929

Safety and Pharmacokinetics of IV CR845 in Hemodialysis Patients, and Its Efficacy in Patients With Uremic Pruritus

Cara Therapeutics, Inc.n = 89Jul 2014 to Jul 2015

Pruritus · Uremic Pruritus

Trial page ClinicalTrials.govUpdated 10 Aug 2016

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:35 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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