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Neuropathic PainPhase 1NCT03809234

Pgp Transporter and CNS Biodistribution of Ondansetron in Healthy Volunteers

A Phase 1 study testing Ondansetron 8mg with Saline & Tariquidar and Ondansetron 16mg with Saline & Tariquidar in people with Neuropathic Pain, run by Washington University School of Medicine at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

To determine the time-course of plasma and CSF concentrations of intravenous (IV) ondansetron in healthy subjects, with and without selective inhibition of Pgp efflux transporter. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Neuropathic Pain
What is being tested?
Ondansetron 8mg with Saline & Tariquidar and Ondansetron 16mg with Saline & Tariquidar
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
14 participants
Where
1 siteUnited States
Study dates
20 May 2019to 30 Nov 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Age 18-50;
  • Body mass index between 18.5 and 30;
  • Good general health with no remarkable medical conditions;
  • Able and willing to provide informed consent.

Who cannot join

  • Current pregnancy or lactation;
  • Known history of hepatic, renal, or cardiac disease, including Long QT Syndrome, cardiac arrhythmias or QTc interval >450msec;
  • Known hypertension, endocrine disorders (such as diabetes mellitus), chronic pain, hematologic disorders, or psychiatric conditions requiring medications;
  • Abnormal vital signs at screening visit, including:
  • HR <40 or >100
  • SBP < 90mmHg or >150mmHg
Show all 32Show fewer
  • DBP > 100mmHg
  • Abnormal troponin values at screening visit
  • Abnormal complete blood count (CBC) or comprehensive metabolic panel (CMP) values at screening visit that could affect drug pharmacokinetics, or suggest undiagnosed medical condition which would increase the risk of complications resulting from this study.
  • Any contraindication for ondansetron administration;
  • Peri- or post-menopausal women experiencing symptoms such as hot flashes;
  • Contraindication to intrathecal catheter placement, such as known coagulopathy or history of clotting disorders, history of scoliosis or lumbar fusion, current infection or fever;
  • 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 (or treatment within < 5 half-lives) with any medication, including QT-prolonging drugs and drugs known to have a significant interaction with ondansetron or P-gp substrates (see below:)
  • Antiretrovirals of Protease inhibitor (e.g. Ritonavir, Saquinavir) or Non-nucleoside reverse transcriptase inhibitors (e.g. Efavirenz, Zidovudine) family.
  • Phenytoin, Carbamazepine, Oxcarbazepine, Rifampin
  • Amiodarone
  • Azole antifungals (e.g. Itraconazole, Fluconazole)
  • Macrolide antibiotics (Erythromycin, Clarithromycin)
  • Cimetidine
  • Non-DHP calcium channel blockers Verapamil and Diltiazem
  • First generation antipsychotic medications Thioridazine, Haloperidol, Chlorpromazine, and Pimozide
  • Second generation antipsychotic medications Ziprasidone and Quetiapine
  • Antihistamine Terfenadine
  • Antidepressants Trazodone, Bupropion, monoamine oxidase inhibitors, Mirtazapine
  • Antiarrhythmics Propafenone, Flecainide, and Procainamide
  • Fluoroquinolone antibiotics Norfloxacin, Ofloxacin, and Ciprofloxacin
  • Cisapride
  • Fentanyl, Lithium, Tramadol
  • Intravenous Methylene blue
  • Other strong inhibitors or inducers of Cytochromes P450 2D6 or 3A4.
  • Other strong inhibitors or inducers of P-glycoprotein

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University in St. Louis

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Effects of Pgp Transporter Inhibition on CNS Biodistribution of Ondansetron in Healthy Volunteers

To determine the time-course of plasma and CSF concentrations of intravenous (IV) ondansetron in healthy subjects, with and without selective inhibition of Pgp efflux transporter.

Read the detailed description

The study hypothesis is that inhibition of Pgp efflux transporters will increase the CNS bio-distribution of the 5-HT3R antagonist ondansetron.

Specifically:

  1. Intravenous administration of ondansetron is expected to yield low CSF exposure.
  2. Co-administration of ondansetron with intravenous tariquidar, an inhibitor of Pgp efflux transporters, will result in increased CSF exposure of ondansetron.
Being tested
Ondansetron 8mg with Saline & Tariquidar, Ondansetron 16mg with Saline & Tariquidar
Medical subject headings
Neuralgia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ondansetron 8mg with Saline & TariquidarDrug

    Each participant will receive two IV infusions of ondansetron, 24 hours apart. In the first and second sessions, respectively, placebo (D5W) or tariquidar (4mg/kg dose in D5W) 22 will be administered IV over 60 minutes. Ondansetron will be diluted in 50mL 0.9% normal saline, and tariquidar will be diluted in 250mL D5W.

  • Ondansetron 16mg with Saline & TariquidarDrug

    Each participant will receive two IV infusions of ondansetron, 24 hours apart. In the first and second sessions, respectively, placebo (D5W) or tariquidar (4mg/kg dose in D5W) 22 will be administered IV over 60 minutes. Ondansetron will be diluted in 50mL 0.9% normal saline, and tariquidar will be diluted in 250mL D5W.

Study groups in NCT03809234
Study groupRoleWhat they receive
Ondansetron with TariquidarExperimentalThe participants will receive an IV ondansetron infusion with tariquidar. Participants will receive either 8mg or 16 mg of iv ondansetron, with 4mg/kg tariguidar.
Receives: Drug: Ondansetron 8mg with Saline & Tariquidar; Drug: Ondansetron 16mg with Saline & Tariquidar
Ondansetron with PlaceboPlacebo comparatorThe participants will receive an IV ondansetron infusion with D5W as placebo. Participants will receive either 8mg or 16 mg of iv ondansetron.
Receives: Drug: Ondansetron 8mg with Saline & Tariquidar; Drug: Ondansetron 16mg with Saline & Tariquidar

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CSF penetration of ondansetron with and without tariquidar - area under the curve (AUC)

    CSF penetration of intravenous ondansetron will be determined as AUCCSF0-∞ of ondansetron, and compared between the two sessions, with and without tariquidar

    Measured: 48 hours

Secondary outcomes (3)

  1. Cmax CSF

    Maximum CSF concentration (Cmax CSF) of ondansetron, compared between the sessions

    Measured: 48 hours

  2. CSF:plasma concentration ratio

    CSF:plasma concentration ratio of ondansetron, compared between the two sessions

    Measured: 48 hours

  3. Plasma Cmax

    Maximum plasma concentration (Cmax) of ondansetron, compared between the sessions

    Measured: 48 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2019
  2. Study start20 May 2019
  3. Primary completion30 Nov 2020
  4. Study completion30 Nov 2020

Why it stopped: Adverse effects related to study procedure (not study drug)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03809234
Sponsor's protocol ID
201811167
Status last verified
Mar 2022
First submitted
14 Jan 2019
Last updated
7 Apr 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 20849570

  • 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.

    PubMed 22395856

  • Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015 Feb;14(2):162-73. doi: 10.1016/S1474-4422(14)70251-0. Epub 2015 Jan 7.

    PubMed 25575710

  • Dogrul A, Ossipov MH, Porreca F. Differential mediation of descending pain facilitation and inhibition by spinal 5HT-3 and 5HT-7 receptors. Brain Res. 2009 Jul 14;1280:52-9. doi: 10.1016/j.brainres.2009.05.001. Epub 2009 May 8.

    PubMed 19427839

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ondansetron 8mg with Saline & Tariquidar and Ondansetron 16mg with Saline & Tariquidar in people with Neuropathic Pain, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Adverse effects related to study procedure (not study drug)). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CSF penetration of ondansetron with and without tariquidar - area under the curve (AUC) (time frame: 48 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03809234, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2022.

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