What side effects are associated with this type of intervention?

Common treatments for itching, particularly those similar to Difelikefalin, include opioid antagonists like naltrexone and naloxone, and other medications such as sertraline and rifampin. Known side effects of opioid antagonists can include gastrointestinal issues, dizziness, and in some cases, pain as a complication. Sertraline, an SSRI, may cause nausea, insomnia, and sexual dysfunction. Rifampin can lead to liver dysfunction, gastrointestinal disturbances, and allergic reactions. It is important to discuss these potential side effects with a healthcare provider to determine the best treatment option.

What prior FDA approvals exist?

FDA-approved treatments for itching include opioid antagonists such as naltrexone and naloxone, which have been used for pruritus associated with cholestasis. Additionally, sertraline, a selective serotonin reuptake inhibitor (SSRI), has been approved for treating cholestatic pruritus. These treatments are somewhat related to Difelikefalin, as they also target neurotransmitter pathways involved in the sensation of itch.

What other types of research exist?

Promising alternatives to Difelikefalin for treating itching include: 1) Sertraline, which has shown efficacy in treating antihistamine-refractory uremic pruritus and cholestatic pruritus. 2) Paroxetine and fluvoxamine, which have been effective in treating chronic pruritus. 3) Pregabalin, which has been used for post-burn pruritus. 4) Thalidomide, which has been used for severe paraneoplastic pruritus. These alternatives have demonstrated potential in clinical studies and may be considered for treatment in 2024.

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Opioid Analgesic

Difelikefalin for Itching in Chronic Kidney Disease

Verified Trial

Phase 3

Waitlist Available

Research Sponsored by Cara Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subject self-reports experiencing daily or near-daily pruritus for at least 6 months prior to screening.

Inadequate response to current or prior topical treatments (including emollients) for pruritus prior to screening.

Must not have

New or change of treatment received for itch, including antihistamines and corticosteroids (oral, intravenous, or topical), within 14 days prior to screening.

Timeline

Screening 4 weeks

Treatment 12 weeks

Follow Up 1 week

Awards & highlights

Pivotal Trial

Summary

This trial tests a pill called difelikefalin to help reduce severe itching in patients with advanced kidney disease. The pill works by calming the nerves that cause itchiness. Difelikefalin is recently approved for treating itching in chronic kidney disease patients.

Who is the study for?

This trial is for adults with advanced stage 4 or 5 chronic kidney disease who have been dealing with daily itching for at least six months and haven't found relief from topical treatments. It's not open to those about to undergo dialysis, receive a kidney transplant, or who have recently changed their itch medication.

What is being tested?

The study tests if Difelikefalin tablets can reduce itch intensity in patients compared to a placebo. Participants will be randomly assigned to either the drug or placebo group and evaluated over a 12-week period, followed by an optional extension phase of up to one year.

What are the potential side effects?

While specific side effects are not listed here, participants may experience adverse reactions related to Difelikefalin which could include typical drug-related symptoms such as nausea, dizziness, or headaches.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have had itchy skin almost every day for the last 6 months.

Select...

My itchiness didn't improve with creams or lotions.

Select...

My kidney disease is in stage 4 or 5.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I haven't started or changed itch treatment in the last 14 days.

Timeline

Screening ~ 4 weeks1 visit

Treatment ~ 12 weeks4 visits

Follow Up ~ 1 week1 visit

Screening ~ 4 weeks

Treatment ~ 12 weeks

Follow Up ~1 week

This trial's timeline: 4 weeks for screening, 12 weeks for treatment, and 1 week for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS score at Week 12 of Treatment Period 1

Secondary study objectives

Efficacy Assessment Phase (Treatment Period 1): Change from baseline in Sleep Quality Questionnaire score at the end of Week 12 of Treatment Period 1.

Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the WI-NRS at Week 4 of Treatment Period 1.

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Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Difelikefalin 1 mg Oral TabletExperimental Treatment1 Intervention

Patients receive oral difelikefalin 1 mg once daily

Group II: Placebo Oral TabletPlacebo Group1 Intervention

Patients receive oral placebo once daily

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for itching, particularly those similar to Difelikefalin, include kappa opioid receptor agonists, bile acid sequestrants, opioid antagonists, and selective serotonin reuptake inhibitors (SSRIs). Kappa opioid receptor agonists, like Difelikefalin, work by activating kappa opioid receptors, which can reduce the sensation of itch by modulating the nervous system's response to itch stimuli. Bile acid sequestrants, such as cholestyramine, bind bile acids in the gut, reducing their reabsorption and thereby decreasing itch associated with liver conditions. Opioid antagonists, like naltrexone, block opioid receptors, which can help alleviate itch by counteracting the itch-promoting effects of endogenous opioids. SSRIs, such as sertraline, increase serotonin levels, which can help modulate the perception of itch. Understanding these mechanisms is crucial for patients as it helps tailor treatments to the underlying cause of their itching, potentially improving efficacy and reducing side effects.

Efficacy and Safety of Difelikefalin in Japanese Patients With Moderate to Severe Pruritus Receiving Hemodialysis: A Randomized Clinical Trial.Post-marketing surveillance study of the safety and efficacy of nalfurafine hydrochloride (Remitch® capsules 2.5 μg) in 3,762 hemodialysis patients with intractable pruritus.