Topical Tripelennamine 1% Cream Versus Diphenhydramine 1% Cream for the Relief of Histamine-Induced Itching: A Proof Concept Study in Healthy Adults.

NCT07778472 | Completed Early Phase 1 FDA Drug

• 1 other identifier: IIIc, 01.21.2025
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine whether topical tripelennamine 1% cream can relieve histamine-induced itching and whether it is more effective than diphenhydramine 1% cream in healthy adults aged 18 to 50 years. The main questions it aims to answer are:

• Does tripelennamine 1% cream reduce the intensity, duration, and peak severity of histamine-induced itch as measured by a visual analog scale (VAS)?
• Does tripelennamine 1% cream reduce the histamine-induced wheal and flare skin responses compared with diphenhydramine 1% cream and vehicle control? Researchers will compare tripelennamine 1% cream, diphenhydramine 1% cream, and a vehicle control cream base to see if tripelennamine provides greater relief of histamine-induced itching and skin reactions. Participants will:
• Have four test areas marked on their forearms.
• Receive topical application of tripelennamine 1% cream, diphenhydramine 1% cream, and vehicle control cream to randomized test sites.
• Undergo a histamine challenge administered through iontophoresis after treatment application.
• Rate their itch intensity every minute using a 0 to 10 visual analog scale until the itch subsides.
• Have wheal and flare skin reactions assessed every 5 minutes for up to 20 minutes, including photographs and videos of the reactions.
• Report any adverse events for up to one week after study completion.

Conditions

Healthy

Keywords

Tripelennamine; Diphenhydramine; Histamine; Itch; VAS; Iontophoresis

Outcome Measures

Primary Outcomes (1)

• VAS

  The effectiveness of tripelennamine 1% cream compared to diphenhydramine 1% cream in relieving histamine-induced itching was determined using a visual analogue scale for pruritus (VAS) as an endpoint. The following parameters were determined from the VAS itch score vs time curves: area under the curve, peak VAS itch score and duration of itch.

  Subjects rated their itch intensity every 60 seconds until the itch sensation had completely subsided using a visual analog scale (VAS) for 60 minutes.

Secondary Outcomes (1)

• Histamine Triple Response

  Research assistants rated the magnitude of the wheal and flare in 5-minute intervals for up to 20 minutes using a rating of 1-mild, 2-moderate, 3-severe.

Study Arms (3)

Vehicle control cream base

PLACEBO COMPARATOR

Participants received a single topical application of vehicle cream base prior to histamine iontophoresis to serve as a control condition.

Drug: Vehicle Control Cream Base

Diphenhydramine 1% topical cream

ACTIVE COMPARATOR

Participants received a single topical application of diphenhydramine 1% cream prior to histamine iontophoresis to evaluate its effect on histamine-induced itch and skin reactions.

Drug: Diphenhydramine

Tripelennamine 1% topical cream

EXPERIMENTAL

Participants received a single topical application of tripelennamine 1% cream prior to histamine iontophoresis to evaluate its effect on histamine-induced itch and skin reactions.

Drug: Tripelennamine

Interventions

Tripelennamine DRUG

Tripelennamine 1% topical cream applied to the skin of one arm of an individual 15 minutes before the application of iontophoretically administered histamine 2% gel.

Also known as: Pyribenzamine

Tripelennamine 1% topical cream

Diphenhydramine DRUG

Diphenhydramine 1% topical cream applied to the skin of one arm of an individual 15 minutes before the application of iontophoretically administered histamine 2% gel.

Diphenhydramine 1% topical cream

Vehicle Control Cream Base DRUG

Approximately 0.2 g of vehicle cream base without antihistamine was applied topically to designated forearm test areas. The cream remained on the skin for 15 minutes before histamine iontophoresis was performed.

Vehicle control cream base

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be in general good health with no disease or physical conditions that would impair evaluation of itch and pain perception.
• No history of chronic itch or pain.
• Must abstain from the use of any systemic or topical antihistamine, steroid, or pain relief medications from the week prior to the study till the completion of the study.
• Must abstain from the use of moisturizers on the arms 24 hours before study visit.

You may not qualify if:

• Inability to complete the required measures.
• The presence of an itchy skin disease.
• Diagnosis of disease that would affect itch or pain perception (e.g. neuropathies).
• Currently enrolled in any investigational study in which the subject is receiving any type of drug, biological, or non-drug therapy.
• Use of oral, topical analgesics, or other medications known to interfere with itch or pain perception in the week prior to the study and throughout the study (e.g. antihistamines, anesthetics, opioids, neuroleptics, etc.).
• Use of emollients on the arms a week prior to the study and throughout the study.
• Known allergies to tripelennamine and/or diphenhydramine.
• Pregnant women. (Women of childbearing potential will undergo an hCG pregnancy test).

Sponsors & Collaborators

• Palm Beach Atlantic University: lead

Study Sites (1)

Palm Beach Atlantic University

West Palm Beach, Florida, 33401, United States

Location

MeSH Terms

Conditions

Pruritus

Interventions

Tripelennamine; Diphenhydramine

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Aminopyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• David M Compton, PhD

  Palm Beach Atlantic University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: randomized (to do with the arm of an individual, ie left or right arm), double-blind, vehicle-controlled crossover human study

Study Record Dates

• First Submitted: August 17, 2026
• First Posted: August 21, 2026
• Study Start: February 24, 2025
• Primary Completion: September 18, 2025
• Study Completion: September 18, 2025
• Last Updated: August 21, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Beginning 6 months following publication of primary results and ending 5 years after publication.
• Access Criteria: Available to qualified researchers upon reasonable request, review and approval of a research proposal, and execution of a Data Use Agreement.

Locations

US (1)