Effect of difelikefalin, a selective kappa opioid receptor agonist, on respiratory depression: A randomized, double-blind, placebo-controlled trial.

Viscusi ER, Torjman MC, Munera CL, Stauffer JW, Setnik BS, Bagal SN

Clinical and translational science21 Jul 2021Cited by 26 (Europe PMC)

PMID33982405PMCIDPMC8504812DOI10.1111/cts.13042PepBankPUB-33982405

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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. Results still quote short attributed sentences.

Results from this study12

12 results from studies that gave the peptide. 12 results from people.

01HumanRandomized controlled trialSafety outcome
In healthy volunteers, neither difelikefalin nor placebo met the respiratory-depression criterion: ETCO2 rise ≥10 mm Hg versus baseline or ETCO2 >50 mm Hg sustained ≥30 seconds.
In plain wordsIn healthy volunteers, neither difelikefalin nor placebo caused carbon dioxide increases that met the respiratory-depression criterion.
Peptide
Difelikefalin
Outcome
No significant changeIncreased ETCO2 respiratory-depression threshold
Study
n = 15
Comparator
Placebo
Analysis
Primary
Outcome group
Adverse events · Respiratory
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Source sentences
Summary
No subject on placebo or difelikefalin met the increased ETCO₂ or reduced SpO₂ primary end point criteria for respiratory depression.
3 context sentences(design, population, supporting numbers)
Summary · context
incidence of increased end-tidal carbon dioxide (ETCO₂ ) greater than or equal to 10 mm Hg versus baseline or a level greater than 50 mm Hg sustained greater than or equal to 30 seconds
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240501
02HumanRandomized controlled trialSafety outcome
In healthy volunteers, neither difelikefalin nor placebo met the respiratory-depression criterion of oxygen saturation below 92% sustained for at least 30 seconds.
In plain wordsIn healthy volunteers, neither difelikefalin nor placebo caused oxygen saturation decreases that met the respiratory-depression criterion.
Peptide
Difelikefalin
Outcome
No significant changeReduced SpO2 respiratory-depression threshold
Study
n = 15
Comparator
Placebo
Analysis
Primary
Outcome group
Adverse events · Respiratory
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Source sentences
Summary
No subject on placebo or difelikefalin met the increased ETCO₂ or reduced SpO₂ primary end point criteria for respiratory depression.
3 context sentences(design, population, supporting numbers)
Summary · context
incidence of reduction in saturation of peripheral oxygen (SpO₂ ) to less than 92% sustained greater than or equal to 30 seconds.
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240502
03HumanRandomized controlled trialSafety outcome
In healthy volunteers, no difelikefalin or placebo recipient met the reduced respiratory rate criterion.
In plain wordsIn healthy volunteers, neither difelikefalin nor placebo met the reduced breathing rate criterion.
Peptide
Difelikefalin
Outcome
No significant changeReduced respiratory rate criterion
Study
n = 15
Comparator
Placebo
Analysis
Secondary
Outcome group
Adverse events · Respiratory
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Source sentences
Summary
No subject met the reduced respiratory rate criterion or experienced clinically significant changes in ETCO₂ , SpO₂ , or respiratory rate.
2 context sentences(design, population, supporting numbers)
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240504
04HumanRandomized controlled trialSafety outcome
In healthy volunteers, no difelikefalin or placebo recipient experienced clinically significant end-tidal carbon dioxide changes.
In plain wordsIn healthy volunteers, neither difelikefalin nor placebo produced clinically significant carbon dioxide changes.
Peptide
Difelikefalin
Outcome
No significant changeClinically significant ETCO2 change
Study
n = 15
Comparator
Placebo
Outcome group
Adverse events · Respiratory
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Source sentences
Summary
No subject met the reduced respiratory rate criterion or experienced clinically significant changes in ETCO₂ , SpO₂ , or respiratory rate.
2 context sentences(design, population, supporting numbers)
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240505
05HumanRandomized controlled trialSafety outcome
In healthy volunteers, no difelikefalin or placebo recipient experienced clinically significant oxygen saturation changes.
In plain wordsIn healthy volunteers, neither difelikefalin nor placebo produced clinically significant oxygen saturation changes.
Peptide
Difelikefalin
Outcome
No significant changeClinically significant SpO2 change
Study
n = 15
Comparator
Placebo
Outcome group
Adverse events · Respiratory
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Source sentences
Summary
No subject met the reduced respiratory rate criterion or experienced clinically significant changes in ETCO₂ , SpO₂ , or respiratory rate.
2 context sentences(design, population, supporting numbers)
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240506
06HumanRandomized controlled trialSafety outcome
In healthy volunteers, no difelikefalin or placebo recipient experienced clinically significant respiratory rate changes.
In plain wordsIn healthy volunteers, neither difelikefalin nor placebo produced clinically significant breathing rate changes.
Peptide
Difelikefalin
Outcome
No significant changeClinically significant respiratory rate change
Study
n = 15
Comparator
Placebo
Outcome group
Adverse events · Respiratory
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Source sentences
Summary
No subject met the reduced respiratory rate criterion or experienced clinically significant changes in ETCO₂ , SpO₂ , or respiratory rate.
2 context sentences(design, population, supporting numbers)
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240507
07HumanNon-randomized trialSafety outcome
In healthy volunteers, respiratory measures remained near baseline during 4-h observations in every group, including difelikefalin and placebo.
In plain wordsIn healthy volunteers, respiratory measures remained near baseline for 4-h in both difelikefalin and placebo groups.
Peptide
Difelikefalin
Outcome
No significant changeRespiratory measures near baseline
Study
n = 15
Comparator
Baseline
Outcome group
Adverse events · Respiratory
Studied dose
1.0 and 5.0 mcg/kg · intravenous · 4-h postdose observationAs given in this study (human).
Source sentences
Summary
All respiratory measures in each group remained near baseline values during 4-h postdose observations.
2 context sentences(design, population, supporting numbers)
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240503
08HumanNon-randomized trialSafety outcome
In healthy volunteers, paresthesia was among the most common difelikefalin treatment-emergent adverse events, reported in ≥20% of subjects.
In plain wordsIn healthy volunteers, tingling was among the most common difelikefalin adverse events, reported in ≥20% of subjects.
Peptide
Difelikefalin
Outcome
Direction not reportedParesthesia
Study
n = 15
Outcome group
Adverse events · Nervous system and cognition
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Measurements
Subjects with paresthesia
≥ 20%
difelikefalin arms, TEAEs reported in at least this share
Source sentences
Summary
The most commonly reported treatment-emergent AEs (TEAEs; ≥20% of subjects) were paresthesia, hypoesthesia, and somnolence in the difelikefalin arms.
2 context sentences(design, population, supporting numbers)
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240508
09HumanNon-randomized trialSafety outcome
In healthy volunteers, hypoesthesia was among the most common difelikefalin treatment-emergent adverse events, reported in ≥20% of subjects.
In plain wordsIn healthy volunteers, reduced sensation was among the most common difelikefalin adverse events, reported in ≥20% of subjects.
Peptide
Difelikefalin
Outcome
Direction not reportedHypoesthesia
Study
n = 15
Outcome group
Adverse events · Nervous system and cognition
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Measurements
Subjects with hypoesthesia
≥ 20%
difelikefalin arms, TEAEs reported in at least this share
Source sentences
Summary
The most commonly reported treatment-emergent AEs (TEAEs; ≥20% of subjects) were paresthesia, hypoesthesia, and somnolence in the difelikefalin arms.
2 context sentences(design, population, supporting numbers)
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240509
10HumanNon-randomized trialSafety outcome
In healthy volunteers, somnolence was among the most common difelikefalin treatment-emergent adverse events, reported in ≥20% of subjects.
In plain wordsIn healthy volunteers, sleepiness was among the most common difelikefalin adverse events, reported in ≥20% of subjects.
Peptide
Difelikefalin
Outcome
Direction not reportedSomnolence
Study
n = 15
Outcome group
Adverse events · Nervous system and cognition
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Measurements
Subjects with somnolence
≥ 20%
difelikefalin arms, TEAEs reported in at least this share
Source sentences
Summary
The most commonly reported treatment-emergent AEs (TEAEs; ≥20% of subjects) were paresthesia, hypoesthesia, and somnolence in the difelikefalin arms.
2 context sentences(design, population, supporting numbers)
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240510
11HumanNon-randomized trialSafety outcome
In healthy volunteers, all treatment-emergent adverse events, including those with difelikefalin, were mild.
In plain wordsIn healthy volunteers, all adverse events, including those with difelikefalin, were mild.
Peptide
Difelikefalin
Outcome
Not applicableAdverse event severity
Study
n = 15
Outcome group
Adverse events · Whole body
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Source sentences
Summary
All TEAEs were mild and resolved without intervention.
2 context sentences(design, population, supporting numbers)
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240511
12HumanNon-randomized trialSafety outcome
In healthy volunteers, all treatment-emergent adverse events, including those with difelikefalin, resolved without intervention.
In plain wordsIn healthy volunteers, all adverse events, including those with difelikefalin, resolved without treatment.
Peptide
Difelikefalin
Outcome
Not applicableAdverse event resolution
Study
n = 15
Outcome group
Adverse events · Whole body
Studied dose
1.0 and 5.0 mcg/kg · intravenousAs given in this study (human).
Source sentences
Summary
All TEAEs were mild and resolved without intervention.
2 context sentences(design, population, supporting numbers)
Summary · context
This single-center, randomized, double-blind, placebo-controlled, three-way crossover study enrolled healthy, nonsmoking volunteers.
Summary · context
Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period.
Report a problemFND-3398240512

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

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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