Tariquidar-ondansetron Combination in Neuropathic Pain

NCT04603066 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 202008183
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective, randomized, double-blind, placebo controlled, cross-over proof of concept study. To determine the pharmacokinetics and tolerability of co-administration of 5-HT3R antagonist ondansetron with a P-glycoprotein inhibitor tariquidar, in patients with neuropathic pain.

Conditions

Neuropathic Pain

Outcome Measures

Primary Outcomes (2)

• Concertation-time Profile of Ondansetron in Plasma, Measured by the Area Under the Concentration-time Curve (AUC)

  AUCinf for Ondansetron concentration in plasma based on venous blood sampling for plasma concentrations of ondansetron obtained at 0, 15, 30, 60, 90, 120, 180, and 240 minutes from the beginning of ondansetron infusion.

  Measurements over 240 minutes, extrapolated to infinity

• Cerebrospinal Fluid to Plasma Concentration Ratio of Ondansetron

  The level of ondansetron in plasma and CSF (cerebrospinal fluid) in samples, taken around the same time, was measured, and the ratio of the two values was calculated. This ratio (partition coefficient, Kp) of ondansetron, compared between the two sessions, with placebo vs tariquidar

  anytime between 0-240 minutes

Secondary Outcomes (4)

• % Change in Pain Intensity

  baseline to 90 minutes after ondansetron IV infusion

• Conditioned Pain Modulation (CPM) Magnitude (ΔCPM)

  Baseline and 90 minutes after the end of ondansetron infusion

• Correlation Between CPM Magnitude (ΔCPM) and Change in Pain Intensity

  0-240 min from infusion

• Change in Neuropathic Pain Symptom Inventory (NPSI) Score

  baseline to 70 min after infusion

Study Arms (2)

Ondansetron/Placebo first, then Ondansetron/Tariquidar

OTHER

The study group where patients received Ondansetron with Placebo during Visit 1, and after a washout period of 3 weeks Ondansetron with Tariquidar at Visit 2 per the randomization schedule. Ondansetron 16 mg was administered IV over 60 minutes with placebo (D5W) or with tariquidar (4mg/kg dose in D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.

Drug: Ondansetron 16 mg with Tariquidar; Drug: Ondansetron 16 mg with Placebo

Ondansetron/Tariquidar first, then Ondansetron/Placebo

OTHER

The study group where patients received Ondansetron with Tariquidar during Visit 1, and after 3 weeks of washout period Ondansetron with Placebo at Visit 2 per the randomization schedule. Ondansetron 16 mg was administered IV over 60 minutes with tariquidar (4mg/kg dose in D5W) or with placebo (D5W). Ondansetron was diluted in 100mL 0.9% normal saline, and tariquidar was diluted in 500mL D5W.

Drug: Ondansetron 16 mg with Tariquidar; Drug: Ondansetron 16 mg with Placebo

Interventions

Ondansetron 16 mg with Tariquidar DRUG

In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.

Also known as: Ondansetron/Tariquidar

Ondansetron/Placebo first, then Ondansetron/Tariquidar; Ondansetron/Tariquidar first, then Ondansetron/Placebo

Ondansetron 16 mg with Placebo DRUG

In randomized order, each participant will receive two IV infusions of ondansetron, 3 weeks apart; one with placebo (D5W), and one with tariquidar (4mg/kg dose in D5W) administered IV over 60 minutes. Ondansetron will be diluted in 100mL 0.9% normal saline, and tariquidar will be diluted in 500mL D5W.

Also known as: Ondansetron/ Placebo

Ondansetron/Placebo first, then Ondansetron/Tariquidar; Ondansetron/Tariquidar first, then Ondansetron/Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65;
• Documented diagnosis of neuropathic pain due to damage or disease affecting the peripheral nervous system;
• At least Probable neuropathic pain grading1;
• Pain duration \>3 months;
• Average pain intensity ≥4 on 0-10 numerical rating scale (NRS).

You may not qualify if:

• Current pregnancy or lactation;
• Moderate-severe kidney or liver dysfunction;
• Active cardiac arrhythmias (non-sinus rhythm), Long QT syndrome, or QTc interval \>450msec;
• Congestive heart failure
• Abnormal troponin values at screening visit;
• Current treatment with MAO inhibitors, mirtazapine, SSRI antidepressants, or SNRI medications duloxetine or venlafaxine;
• Current treatment with tapentadol, tramadol, or fentanyl;
• Current treatment with P-glycoprotein substrate drugs with narrow therapeutic window, e.g. digoxin;
• Current treatment with tricyclic antidepressant medications (e.g. amitriptyline, desipramine, imipramine) at a dose \>25mg/day;
• Ongoing use of any of the following medications with known effects on Pgp function: carbamazepine, phenytoin, phenobarbital, cyclosporine, clarithromycin, erythromycin, ritonavir, verapamil, rifampicin, St. John's wort;
• Current treatment with QT-prolonging drugs, and drugs known to have a significant interaction with ondansetron or other P-glycoprotein substrates (see section 2.3.3.);
• Current treatment with anticoagulant drugs;

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine/Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Related Publications (3)

• Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice ASC, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016 Aug;157(8):1599-1606. doi: 10.1097/j.pain.0000000000000492.

  PMID: 27115670 BACKGROUND

• Yawn BP, Wollan PC, Weingarten TN, Watson JC, Hooten WM, Melton LJ 3rd. The prevalence of neuropathic pain: clinical evaluation compared with screening tools in a community population. Pain Med. 2009 Apr;10(3):586-93. doi: 10.1111/j.1526-4637.2009.00588.x. Epub 2009 Mar 17.

  PMID: 20849570 BACKGROUND

• Smith BH, Torrance N. Epidemiology of neuropathic pain and its impact on quality of life. Curr Pain Headache Rep. 2012 Jun;16(3):191-8. doi: 10.1007/s11916-012-0256-0.

  PMID: 22395856 BACKGROUND

MeSH Terms

Conditions

Neuralgia

Interventions

Ondansetron; tariquidar

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Limitations and Caveats

Due to ethical considerations, cerebrospinal fluid (CSF) sampling was optional in the study, therefore data on plasma/CSF ratio is not available for all patients. A total of 24 patients were enrolled out of 28 participant planned.

Results Point of Contact

• Title: Simon Haroutounian
• Organization: Washington University in St Louis

sharout@wustl.edu

3132861715

Study Officials

• Simon Haroutounian, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Prospective, randomized, double blind, crossover study

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: October 26, 2020
• Study Start: January 31, 2021
• Primary Completion: October 21, 2023
• Study Completion: November 3, 2023
• Last Updated: August 14, 2025
• Results First Posted: August 14, 2025

Record last verified: 2025-07

Locations

US (1)