Tariquidar-ondansetron Combination in Neuropathic Pain

The Washington University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Neuropathic Pain

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

Study type: Interventional

Funder types: Other

Identifiers

NCT04603066

202008183

Details and patient eligibility

About

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.

Full description

The investigators hypothesize that co-administration of a 5-HT3 receptor antagonist ondansetron (single 16mg dose) with p-glycoprotein inhibitor tariquidar (single 4mg/kg dose) vs placebo in a cross-over prospective randomized study, will:

1. Be tolerable in patients with neuropathic pain.
2. Increase the cerebrospinal fluid (CSF) to plasma ratio of ondansetron after intravenous administration, compare to ondansetron alone
3. Result in a greater reduction in pain intensity than with ondansetron alone.

Enrollment: 24 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Current pregnancy or lactation;
2. Moderate-severe kidney or liver dysfunction;
3. Active cardiac arrhythmias (non-sinus rhythm), Long QT syndrome, or QTc interval >450msec;
4. Congestive heart failure
5. Abnormal troponin values at screening visit;
6. Current treatment with MAO inhibitors, mirtazapine, SSRI antidepressants, or SNRI medications duloxetine or venlafaxine;
7. Current treatment with tapentadol, tramadol, or fentanyl;
8. Current treatment with P-glycoprotein substrate drugs with narrow therapeutic window, e.g. digoxin;
9. Current treatment with tricyclic antidepressant medications (e.g. amitriptyline, desipramine, imipramine) at a dose >25mg/day;
10. 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;
11. 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.);
12. Current treatment with anticoagulant drugs;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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24 participants in 2 patient groups

Ondansetron/Placebo first, then Ondansetron/Tariquidar

Other group

Description:

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.

Treatment:

Drug: Ondansetron 16 mg with Tariquidar

Drug: Ondansetron 16 mg with Placebo

Ondansetron/Tariquidar first, then Ondansetron/Placebo

Other group

Description:

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.

Treatment:

Drug: Ondansetron 16 mg with Tariquidar

Drug: Ondansetron 16 mg with Placebo