Influence of Oxycodone on Individuals Taking an SSRI

NCT05730062 | Unknown Phase 1

• 1 other identifier: P22.052
• Study Type: interventional
• Target: 55
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will determine whether selective serotonin reuptake inhibitors (SSRI) exacerbate opioid induced respiratory depression in patients initiating treatment for underlying conditions such as depression or an anxiety disorder. Next to paroxetine which has been evaluated in a previous study in healthy volunteers sertraline, citalopram and escitalopram will be evaluated with regards to its influence on opioid induced respiratory depression.

Conditions

Opioid Induced Respiratory Depression; Depressive Disorder; Anxiety Disorders

Outcome Measures

Primary Outcomes (1)

• Ve55 Paroxetine 1 week

  After one week of starting Paroxetine, extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be measured, followed by oxycodone or placebo ingestion. The extrapolated ventilation at an end-tidal carbon dioxide concentration of 55 mmHg will be assessed two hours after oxycodone/placebo ingestion. The change from the baseline will be determined.

  two hours following ingestion of the Paroxetine either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.

Secondary Outcomes (5)

• Ve55 Sertraline, Citalopram, Escitalopram 1 week

  two hours following ingestion of the Sertraline or Citalopram or Escitalopram either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.

• Ve55 Paroxetine, Sertraline, Citalopram, Escitalopram at 1 month

  two hours following ingestion of the Sertraline or Citalopram or Escitalopram either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.

• Ve55 over course Treatment

  two hours following ingestion of the Sertraline or Citalopram or Escitalopram either oxycodone or placebo will be administered two hours following ingestion of oxycodone/placebo the change in Ve55 from baseline Ve55 will be evaluated.

• Pupillometry

  Will be determined from pupillometry at t= 0,30,60,90,120,150,180,210,240,270,300 minutes

• Plasma concentration oxycodone

  Will be determined from blood samples drawn at t= 0,15,30,45,60,120,180,240,300 minutes

Study Arms (4)

SSRI 1 week following initiation oxycodone

EXPERIMENTAL

Patients will be included day 4-10 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and will be administered oxycodone 10 mg IR

Drug: Oxycodone Hydrochloride

SSRI 1 week following initiation placebo

PLACEBO COMPARATOR

Patients will be included day 25-45 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and and will be administered placebo comparator

Drug: Placebo

SSRI 1 month following initiation oxycodone

EXPERIMENTAL

Patients will be included day 25-45 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and and will be administered oxycodone 10 mg IR.

Drug: Oxycodone Hydrochloride

SSRI 1 month following initiation placebo

PLACEBO COMPARATOR

Patients will be included day 25-45 following initiation of treatment with either Paroxetine, Sertraline, Escitalopram or Citalopram and and will be administered placebo comparator.

Drug: Placebo

Interventions

Oxycodone Hydrochloride DRUG

Oxycodone 10 mg IR

Also known as: oxynorm

SSRI 1 month following initiation oxycodone; SSRI 1 week following initiation oxycodone

Placebo DRUG

placebo comparator

SSRI 1 month following initiation placebo; SSRI 1 week following initiation placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed the informed consent form (ICF) and able to comply with the study requirements and restrictions listed therein;
• Male and female subjects, age 18 to 75 years, inclusive;
• Women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative serum pregnancy test prior to enrolment and must agree to use a medically acceptable means of contraception from screening through at least 1 month after the last dose of study drug;
• Body Mass Index (BMI) 18 to 35 kg/m2, inclusive;
• Stable as defined by the Investigator, based on a medical evaluation that includes the subject's medical and surgical history, physical examination, vital signs;
• Using sertraline (minimal dose 50 mg), paroxetine minimal dose 20 mg), citalopram (minimal dose 20 mg) or escitalopram (minimal dose 10 mg).

You may not qualify if:

• Currently meet the criteria for diagnosis of moderate or severe substance use disorder according to the DSM-5 criteria on any substances other than caffeine, or nicotine;
• Any active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints;
• Consume, on average, \>27 units/week of alcohol in men and \>20 units/week of alcohol in women (1 unit = 1 glass (250 mL) beer, 125 mL glass of wine or 25 mL of 40% spirit);
• Currently receiving medication-assisted treatment for the treatment of opioid-use disorder;
• Require on-going prescription or over-the-counter medications that are clinically relevant CYP P450 3A4 or CYP P450 2C8 inducers or inhibitors (e.g., rifampicin, azole antifungals \[e.g., ketoconazole\], macrolide antibiotics \[e.g., erythromycin\]);
• Significant traumatic injury, major surgery, or open biopsy within the prior 4 weeks of informed consent;
• History of substance use disorder;
• History of suicidal ideation within 30 days prior to informed consent or history of a suicide attempt in the 6 months prior to informed consent;
• Measured systolic blood pressure greater than 160 or less than 95 mmHg or diastolic pressure greater than 95 mmHg at screening;
• History or presence of allergic response to study medication;
• Treatment with another investigational drug within 3 months prior to dosing or having participated in more than 4 investigational drug studies within 1 year prior to screening;
• Site staff or subjects affiliated with, or a family member of, site staff directly involved in the study.
• Current use of any opioid.
• Opioid use less than 4 weeks prior to dosing with oxycodone in the current study.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Related Publications (7)

• Florian J, van der Schrier R, Gershuny V, Davis MC, Wang C, Han X, Burkhart K, Prentice K, Shah A, Racz R, Patel V, Matta M, Ismaiel OA, Weaver J, Boughner R, Ford K, Rouse R, Stone M, Sanabria C, Dahan A, Strauss DG. Effect of Paroxetine or Quetiapine Combined With Oxycodone vs Oxycodone Alone on Ventilation During Hypercapnia: A Randomized Clinical Trial. JAMA. 2022 Oct 11;328(14):1405-1414. doi: 10.1001/jama.2022.17735.

  PMID: 36219407 BACKGROUND

• Cohen R, Finn H, Steen SN. Effect of diazepam and meperidine, alone and in combination, on respiratory response to carbon dioxide. Anesth Analg. 1969 May-Jun;48(3):353-5. No abstract available.

  PMID: 5815096 BACKGROUND

• Geddes DM, Rudolf M, Saunders KB. Effect of nitrazepam and flurazepam on the ventilatory response to carbon dioxide. Thorax. 1976 Oct;31(5):548-51. doi: 10.1136/thx.31.5.548.

  PMID: 11571 BACKGROUND

• Olsson M, Annerbrink K, Bengtsson F, Hedner J, Eriksson E. Paroxetine influences respiration in rats: implications for the treatment of panic disorder. Eur Neuropsychopharmacol. 2004 Jan;14(1):29-37. doi: 10.1016/s0924-977x(03)00044-0.

  PMID: 14659984 BACKGROUND

• van der Schrier R, Roozekrans M, Olofsen E, Aarts L, van Velzen M, de Jong M, Dahan A, Niesters M. Influence of Ethanol on Oxycodone-induced Respiratory Depression: A Dose-escalating Study in Young and Elderly Individuals. Anesthesiology. 2017 Mar;126(3):534-542. doi: 10.1097/ALN.0000000000001505.

  PMID: 28170358 BACKGROUND

• Xu L, Krishna A, Stewart S, Shea K, Racz R, Weaver JL, Volpe DA, Pilli NR, Narayanasamy S, Florian J, Patel V, Matta MK, Stone MB, Zhu H, Davis MC, Strauss DG, Rouse R. Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat. Clin Transl Sci. 2021 Nov;14(6):2208-2219. doi: 10.1111/cts.13080. Epub 2021 Jun 16.

  PMID: 34080766 BACKGROUND

• Yunusa I, Gagne JJ, Yoshida K, Bykov K. Risk of Opioid Overdose Associated With Concomitant Use of Oxycodone and Selective Serotonin Reuptake Inhibitors. JAMA Netw Open. 2022 Feb 1;5(2):e220194. doi: 10.1001/jamanetworkopen.2022.0194.

  PMID: 35201310 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder; Anxiety Disorders

Interventions

Oxycodone

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Albert Dahan, MD PhD

  LUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rutger van der Schrier, MD

CONTACT

+31 (0)71 5299893; r.m.van_der_schrier@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double (Participant, Outcomes Assessor)
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Model Details: This is a placebo controlled (oxycodone vs placebo) crossover study in patients initiating one of the following SSRIs (Paroxetine, Sertraline, Citalopram, Escitalopram)

Study Record Dates

• First Submitted: January 12, 2023
• First Posted: February 15, 2023
• Study Start: March 15, 2023
• Primary Completion: January 15, 2025
• Study Completion: April 15, 2025
• Last Updated: February 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share