Combined Effect of Pregabalin and Oxycodone, and Lacosamide and Oxycodone, on Breathing

NCT05598905 | Completed Phase 4

• 1 other identifier: P22.044
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Opioids are commonly prescribed for moderate to severe pain. While initially intended for moderate to severe acute and cancer pain, opioids are currently frequently considered and prescribed in chronic noncancer pain. Due to the large increase in opioid prescription rate, the number of unintentional drug overdoses is rapidly increasing, not only in the Unites States but also in the Netherlands. A potential lethal consequence of an opioid overdose is opioid-induced respiratory depression. Additionally, it is well known that opioids are often used (and abused) in combination with other legal or illicit substances, for example alcohol, benzodiazepines, cannabis, neuropathic pain medication including the anticonvulsant pregabaline. There are no high-quality data on the interaction between oxycodone and (neuropathic pain) medication on the ventilatory control system. Case reports and randomized studies show that pregabalin induces respiratory depression when combined with opioids. Some alternatives to pregabalin may have a better safety profile. One such alternative is lacosamide, an antiepileptic with a different mode of action than pregabalin, and effective in the treatment of neuropathic pain. The hypothesis is that in contrast to lacosamide, pregabalin will increase the respiratory depressant effect of low-dose oxycodone. The objective of the study is to quantify the effect of pregabalin and lacosamide on oxycodone-induced respiratory depression. 24 participants will be screened beforehand if subjects meet the inclusion and exclusion criteria. If so, the subjects will visit the hospital twice. On both occasions, participants will take a 10 mg oxycodone tablet and 90 minutes after a capsule of pregabalin or lacosamide. The order of visits will be randomized. During the visits, at set time points the hypercapnic ventilatory response will be measured, relief of nociception, pupil diameter and several side effects other than respiratory depression. There will be a washout period of 7 days between study visits with the study ending after 2 visits. Amendment: In order to get an impression of the effect of 10 mg oxycodone per se, one open label arm of just 10 mg oxycodone was added as a visit 3. Since the procedures in this third arm will be identical to the two blinded arms, no changes will be made to any of the procedures apart from not administering any lacosamide or pregabalin.

Conditions

Opioid-induced Respiratory Depression

Keywords

Oxycodone; Pregabalin; Lacosamide

Outcome Measures

Primary Outcomes (2)

• Ventilation

  The primary endpoint of the study is the change in ventilation at an increased level of CO2

  Study day 1

• Ventilation

  The primary endpoint of the study is the change in ventilation at an increased level of CO2

  Study day 2

Secondary Outcomes (5)

• Level of sedation

  Study day 1

• Pain relief

  Study day 1

• Occurence of nausea/vomiting

  Study day 1

• pupil diameter

  Study day 1

• Baseline ventilation

  Study day 1

Study Arms (3)

Oxycodone + Pregabalin

EXPERIMENTAL

Participants will visit twice. On one visit they will take a 10mg oxycodone tablet and 90 minutes later a 150mg pregabaline capsule.

Drug: Pregabalin 150mg; Drug: Oxycodone 10mg

Oxycodone + Lacosamide

EXPERIMENTAL

Participants will visit twice. On one visit they will take a 10mg oxycodone tablet and 90 minutes later a 150mg Lacosamide capsule.

Drug: Oxycodone 10mg; Drug: Lacosamide 150 mg

Oxycodone

OTHER

Amendment: one open label arm. In order to get an impression of the effect of 10 mg oxycodone per se, one open label arm of just 10 mg oxycodone as a visit 3 was added.

Drug: Oxycodone 10mg

Interventions

Pregabalin 150mg DRUG

one capsule of 150mg 90 minutes after 10mg of oxycodone

Also known as: Lyrica capsule 150 mg

Oxycodone + Pregabalin

Oxycodone 10mg DRUG

one 10mg tablet

Also known as: Oxycodone tablet 10 mg

Oxycodone; Oxycodone + Lacosamide; Oxycodone + Pregabalin

Lacosamide 150 mg DRUG

one capsule of 150mg 90 minutes after 10mg of oxycodone

Also known as: Vimpat 150 mg capsule

Oxycodone + Lacosamide

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• aged 18-45 years,
• body mass index \< 30 kg.m-2,
• able to understand the written informed consent form,
• able to communicate with the staff,
• able and willing to complete the study procedures,
• signed the informed consent form.

You may not qualify if:

• Presence or history of any medical or psychiatric disease (incl. a history of substance abuse, anxiety, or the presence of a painful syndrome such as fibromyalgia);
• Use of any medication in the three months prior to the study which may influence the outcome of the study as judged by the investigator;
• Use of more than 21 alcohol units per week;
• A positive urinary drug test or a breath alcohol test at screening or on the morning of the experiment;
• Pregnancy, lactating or a positive pregnancy test on the morning of the experiment;
• Participation in another drug trial in the 60 days prior to dosing.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

Location

MeSH Terms

Interventions

Pregabalin; Oxycodone; Lacosamide

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Acetamides; Amides; Acetates

Study Officials

• Marieke Niesters, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind cross-over trial in which the order of visits is randomized. Amendment: In order to get an impression of the effect of 10 mg oxycodone per se, one open label arm of just 10 mg oxycodone as a visit 3 was added.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Double-blind, randomized cross-over design. Amendment: In order to get an impression of the effect of 10 mg oxycodone per se, one open label arm of just 10 mg oxycodone as a visit 3 was added.

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 28, 2022
• Study Start: October 10, 2022
• Primary Completion: January 12, 2024
• Study Completion: January 12, 2024
• Last Updated: June 4, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)