HypercapniaPhase 1NCT05470465
Effect of Selective Serotonin Reuptake Inhibitors (SSRIs) and an Opioid on Ventilation
A Phase 1 study testing Paroxetine and Oxycodone and Escitalopram and Oxycodone in people with Hypercapnia and Ventilatory Depression, run by Food and Drug Administration (FDA) at 1 site in United States.
Trial summary
This study is designed to evaluate the effects of the coadministration of paroxetine or escitalopram with an opioid on ventilation. Ventilation will be assessed using a rebreathing methodology. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypercapnia, Ventilatory Depression
- What is being tested?
- Paroxetine and Oxycodone and Escitalopram and Oxycodone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2022to 17 Sep 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Subject signs an Institutional Review Board (IRB) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
- Subject is a healthy, non-smoking man or woman, 18 to 50 years of age, inclusive, who has a body mass index of 18.5 to 33.0 kg/m2, inclusive, at Screening.
- Subject has normal medical history findings, clinical laboratory results, vital sign measurements, pulse oximetry, 12-lead ECG results, and physical examination findings at screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
- Subject must have a negative test result for alcohol and drugs of abuse at screening and check-in days.
- Subject must test negative for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) by a rapid antigen test at check-in for all study periods. If a subject's test comes back as invalid, the test can be repeated.
- Female subjects must be of non-childbearing potential (confirmed with follicle-stimulating hormone levels > 40 milli-international unit [mIU]/mL) or, if they are of childbearing potential, they must: 1) have been strictly abstinent for 1 month before check-in (Day -1) and agree to remain strictly abstinent for the duration of the study and for at least 1month after the last application of study drug; OR 2) be practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from at least 1 month before check-in (Day -1) until at least 1 month after the end of the study.
- Male subjects must agree to practice 2 highly effective methods of birth control (as determined by the investigator or designee) from at least 1 month before check-in (Day -1) until at least 1 month after the last dose of study drug.
- Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study.
Who cannot join
- Subject has used any prescription or nonprescription drugs (including aspirin or NSAIDs and excluding oral contraceptives and acetaminophen) within 14 days or 5 half-lives (whichever is longer) or complementary and alternative medicines within 28 days before the first dose of study drug. This includes prescription or nonprescription ophthalmic drugs.
- Subject is currently participating in another clinical study of an investigational drug or has been treated with any investigational drug within 30 days or 5 half-lives (whichever is longer) of the compound.
- Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, electronic cigarettes) within 6 weeks of Screening. Subjects must refrain from using these throughout the study.
- Subject has consumed alcohol, xanthine containing products (e.g., tea, coffee, cola), caffeine, grapefruit, or grapefruit juice within 24 h of check-in. Subjects must refrain from ingesting these throughout the study.
- Subject has a history or evidence of a clinically significant disorder, condition, or disease (e.g., cancer, human immunodeficiency virus [HIV], hepatic or renal impairment) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. This includes subjects with any underlying medical conditions that put subjects at increased risk of severe illness from coronavirus disease 2019 (COVID-19) based on the Centers for Disease Control and Prevention (CDC) guidelines.
- Subject has any signs or symptoms at screening or check-in of any study periods that are consistent with COVID-19. Per current CDC recommendations this includes subjects with the symptoms cough or shortness of breath or difficulty breathing, or at least two of the following symptoms: fever, chills, repeated shaking with chills, muscle pain, headache, sore throat or new loss of taste/smell. In addition, the subject has any other findings suggestive of COVID-19 risk in the opinion of the investigator.
Show all 31Show fewer
- Subject has known or suspected allergies or sensitivities to any study drugs.
- Subject has clinical laboratory test results (hematology, serum chemistry and urinalysis) at Screening or period check-in that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator. Clinical laboratory results may be repeated once, as needed, for confirming results at Screening and period check-in.
- Subject has a positive test result at Screening for HIV 1 or 2 antibody, hepatitis C virus antibodies, or hepatitis B surface antigen.
- Subject is unable or unwilling to undergo multiple venipunctures for blood sample collection because of poor tolerability or poor venous access.
- Female subject is currently pregnant or lactating or was within 3 months of before enrollment.
- Subject has a history of opioid or psychotropic drugs within 60 days of the start of the study.
- Subject has a history of asthma that has required medication within the last five years.
- Subject has non-reactive or misshapen pupil(s) or damaged orbit structure or surrounding soft tissue is edematous or has an open lesion.
- Subject has a Mallampati score of >2.
- Subject's Duffin rebreathing data is of poor quality or subject does not agree to remain clean-shaven for all days when the Duffin rebreathing procedure is performed.
- Subject has a history of sleep disorders, Panic disorders, Panic Attacks, Generalized Anxiety Disorder, or any associated Diagnostic and Statistical Manual of Mental Disorders diagnosis or condition.
- Subject has a history of or currently has hypoventilation syndrome or sleep apnea and is on non-invasive ventilation.
- Subject has a history of unexplained syncope, structural heart disease, long QT syndrome, heart failure, myocardial infarction, angina, unexplained cardiac arrhythmia, Torsades de Pointes, ventricular tachycardia, or placement of a pacemaker or implantable defibrillator. Subjects will be also excluded if there is a family history of long QT syndrome (genetically proven or suggested by sudden death of a close relative to cardiac causes at a young age) or Brugada syndrome.
- Subject has a history of suicidal ideation or previous suicide attempts.
- Subject has a safety 12-lead ECG result at Screening or check-in at any study period with evidence of any of the following abnormalities:
- QTc using Fridericia correction (QTcF)>430 msec
- PR interval>220 msec or <120msec
- QRS duration>110 msec
- Second- or third-degree atrioventricular block
- Complete left or right bundle branch block or incomplete right bundle branch block
- Heart rate <50 or >90 beats per minute
- Pathological Q-waves (defined as Q-wave>40 msec)
- Ventricular pre-excitation
- Subject has a skin condition likely to compromise ECG electrode placement.
- Any individual with breast implants.
Trial locations and contacts
1 site in 1 country.
United States1 site
Spaulding Clinical Research
West Bend, Wisconsin, 53095
About this study
Official title: Clinical Study to Investigate the Effect of Administration of Selective Serotonin Reuptake Inhibitors (SSRIs) and an Opioid on Ventilation
This study is designed to evaluate the effects of the coadministration of paroxetine or escitalopram with an opioid on ventilation. Ventilation will be assessed using a rebreathing methodology. This study will evaluate chronic and acute dosing of paroxetine and escitalopram combined with an opioid as well as chronic and acute dosing of the two drugs without coadministration of an opioid.
This study is a 3-period, randomized, placebo-controlled crossover study conducted with 25 healthy participants. Each participant will receive each of the 3 treatments (placebo/oxycodone, paroxetine/oxycodone, escitalopram/oxycodone) in a randomized order.
Read the detailed description
This study is designed to evaluate the effects of the coadministration of paroxetine or escitalopram, two selective serotonin reuptake inhibitors (SSRI), with an opioid on hypercapnic ventilation. Hypercapnic ventilation will be assessed under both hyperoxic and hypoxic conditions using the Duffin rebreathing method. This method allows for critical physiological measurements and thresholds to be captured that can then be used to model the effects of drugs when there are dynamic changes in oxygen partial pressure (PO2) and carbon dioxide partial pressure (PCO2), such as during a real-world opioid overdose.
SSRIs take approximately 3 weeks to reach maximal therapeutic effect, which correlates with the time required for pre-synaptic inhibitory serotonergic receptors to desensitize. Therefore, drug-effects on ventilation should be evaluated under steady state conditions.
This study is randomized, placebo-controlled crossover study which includes three 21-day periods conducted with 25 healthy participants. Participants will receive each of the 3 treatments (placebo/oxycodone, paroxetine/oxycodone, or escitalopram/oxycodone) in a randomized order. Paroxetine dosing will range from 40-60 mg once daily (QD) and escitalopram dosing will range from 20-30 mg QD. Subjects will receive 10 mg oxycodone on three different days each period. Subjects will undergo 6 days of rebreathing and time-matched pupillary assessments along with 3 separate days of ECG assessments each period. Additionally, blood samples will be collected for determination of plasma concentrations for each study drug on days with rebreathing and ECG assessments.
- Conditions
- Hypercapnia, Ventilatory Depression
- Being tested
- Placebo and Oxycodone, Paroxetine and Oxycodone, Escitalopram and Oxycodone
- Medical subject headings
- Hypercapnia, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo and OxycodoneDrug
Participants will receive placebo on days 1-21 for this treatment period. Oxycodone 10 mg (2 x 5 mg tablets) will be administered on days 6, 12, and 21 of this treatment period.
Paroxetine and OxycodoneDrug
Participants will receive 40 mg paroxetine (2 x 20 mg tablets) on days 1-6 and 60 mg paroxetine (3 x 20 mg tablets) on days 7-21 for this treatment period. Oxycodone 10 mg (2 x 5 mg tablets) will be administered on days 6, 12, and 21 of this treatment period.
Escitalopram and OxycodoneDrug
Participants will receive 20 mg escitalopram (2 x 10 mg tablets) on days 1-6 and 30 mg escitalopram (3 x 10 mg tablets) on days 7-21 for this treatment period. Oxycodone 10 mg (2 x 5 mg tablets) will be administered on days 6, 12, and 21 of this treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Treatment A: Placebo | Placebo comparator | Participants will receive placebo on days 1-21 for this treatment period. Oxycodone will be administered on days 6, 12, and 21 of this treatment period. Receives: Drug: Placebo and Oxycodone |
| Treatment B: Paroxetine | Experimental | Participants will receive paroxetine on days 1-21 for this treatment period. Oxycodone will be administered on days 6, 12, and 21 of this treatment period. Receives: Drug: Paroxetine and Oxycodone |
| Treatment C: Escitalopram | Experimental | Participants will receive escitalopram on days 1-21 for this treatment period. Oxycodone will be administered on days 6, 12, and 21 of this treatment period. Receives: Drug: Escitalopram and Oxycodone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minute Ventilation at 55mm Hg End Tidal CO2 (VE55) Under Hyperoxic Conditions on Day 21
Comparison of escitalopram or paroxetine with oxycodone to oxycodone alone. Rebreathing data will be analyzed by regression of the minute ventilation versus partial pressure of end tidal CO2 (PETCO2) data to estimate VE55. Resulting VE55 data will be compared using a linear mixed effects model. Comparison will be at 5 hours on day 21.
Measured: 5 hours on day 21
VE55 Under Hyperoxic Conditions on Day 20
Comparison of escitalopram or paroxetine to placebo. Rebreathing data will be analyzed by regression of the minute ventilation versus partial pressure of end tidal CO2 (PETCO2) data to estimate VE55. Resulting VE55 data will be compared using a linear mixed effects model. Comparison will be at 5 hours on day 20.
Measured: 5 hours on day 20
Secondary outcomes (4)
VE55 Under Hyperoxic Conditions on Day 6
Comparison of escitalopram or paroxetine with oxycodone to oxycodone alone. Rebreathing data will be analyzed by regression of the minute ventilation versus partial pressure of end tidal CO2 (PETCO2) data to estimate VE55. Resulting VE55 data will be compared using a linear mixed effects model. Comparison will be at 5 hours on day 6.
Measured: 5 hours on day 6
VE55 Under Hyperoxic Conditions on Day 12
Comparison of escitalopram or paroxetine with oxycodone to oxycodone alone. Rebreathing data will be analyzed by regression of the minute ventilation versus partial pressure of end tidal CO2 (PETCO2) data to estimate VE55. Resulting VE55 data will be compared using a linear mixed effects model. Comparison will be at 5 hours on day 12.
Measured: 5 hours on day 12
VE55 Under Hyperoxic Conditions on Day 5
Comparison of escitalopram or paroxetine to placebo. Rebreathing data will be analyzed by regression of the minute ventilation versus partial pressure of end tidal CO2 (PETCO2) data to estimate VE55. Resulting VE55 data will be compared using a linear mixed effects model. Comparison will be at 5 hours on day 5.
Measured: 5 hours on day 5
VE55 Under Hyperoxic Conditions on Day 11
Comparison of escitalopram or paroxetine to placebo. Rebreathing data will be analyzed by regression of the minute ventilation versus partial pressure of end tidal CO2 (PETCO2) data to estimate VE55. Resulting VE55 data will be compared using a linear mixed effects model. Comparison will be at 5 hours on day 11.
Measured: 5 hours on day 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2022
- Study start1 Sep 2022
- Primary completion17 Sep 2023
- Study completion17 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for HypercapniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Crossover
- Model description
- This is a 3-period, double-blind, randomized crossover study. The duration of each treatment period will be 21 days in addition to a three-week washout between periods. The duration of study participation will be 106 days (excluding the screening period).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Food and Drug Administration (FDA)
- Sponsor type
- US federal agency
- Collaborators
- Spaulding Clinical Research LLC, Leiden University
- Responsible party
- Sponsor
- Investigators
- Jan Matousek, D.O., Principal investigator, Spaulding Clinical Research LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05470465
- Sponsor's protocol ID
- SCR-012
- Status last verified
- May 2025
- First submitted
- 14 Jul 2022
- Last updated
- 22 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 34080766Rebuck AS. Measurement of ventilatory response to CO2 by rebreathing. Chest. 1976 Jul;70(1 Suppl):118-21. doi: 10.1378/chest.70.1_supplement.118. No abstract available.
PubMed 939123van der Schrier R, Jonkman K, van Velzen M, Olofsen E, Drewes AM, Dahan A, Niesters M. An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers. Br J Anaesth. 2017 Dec 1;119(6):1169-1177. doi: 10.1093/bja/aex295.
PubMed 29029015van 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.
PubMed 28170358Nutt DJ, Forshall S, Bell C, Rich A, Sandford J, Nash J, Argyropoulos S. Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders. Eur Neuropsychopharmacol. 1999 Jul;9 Suppl 3:S81-6. doi: 10.1016/s0924-977x(99)00030-9.
PubMed 10523062Czachura JF, Rasmussen K. Effects of acute and chronic administration of fluoxetine on the activity of serotonergic neurons in the dorsal raphe nucleus of the rat. Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):266-75. doi: 10.1007/s002100000290.
PubMed 10997729Casey K, Duffin J, McAvoy GV. The effect of exercise on the central-chemoreceptor threshold in man. J Physiol. 1987 Feb;383:9-18. doi: 10.1113/jphysiol.1987.sp016392.
PubMed 3116207Duffin J, McAvoy GV. The peripheral-chemoreceptor threshold to carbon dioxide in man. J Physiol. 1988 Dec;406:15-26. doi: 10.1113/jphysiol.1988.sp017365.
PubMed 3151077Dong TW, MacLeod DB, Santoro A, Augustine Z, Barth S, Cooter M, Moon RE. A methodology to explore ventilatory chemosensitivity and opioid-induced respiratory depression risk. J Appl Physiol (1985). 2020 Sep 1;129(3):500-507. doi: 10.1152/japplphysiol.00460.2020. Epub 2020 Jul 16.
PubMed 32673158Read DJ. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med. 1967 Feb;16(1):20-32. doi: 10.1111/imj.1967.16.1.20. No abstract available.
PubMed 6032026Gorman JM, Browne ST, Papp LA, Martinez J, Welkowitz L, Coplan JD, Goetz RR, Kent J, Klein DF. Effect of antipanic treatment on response to carbon dioxide. Biol Psychiatry. 1997 Dec 1;42(11):982-91. doi: 10.1016/s0006-3223(97)00160-1.
PubMed 9386849Bertani A, Perna G, Arancio C, Caldirola D, Bellodi L. Pharmacologic effect of imipramine, paroxetine, and sertraline on 35% carbon dioxide hypersensitivity in panic patients: a double-blind, random, placebo-controlled study. J Clin Psychopharmacol. 1997 Apr;17(2):97-101. doi: 10.1097/00004714-199704000-00006.
PubMed 10950471Robillard R, Saad M, Ray LB, BuJaki B, Douglass A, Lee EK, Soucy L, Spitale N, De Koninck J, Kendzerska T. Selective serotonin reuptake inhibitor use is associated with worse sleep-related breathing disturbances in individuals with depressive disorders and sleep complaints: a retrospective study. J Clin Sleep Med. 2021 Mar 1;17(3):505-513. doi: 10.5664/jcsm.8942.
PubMed 33118928Florian J, Keshishi D, Gershuny V, Salcedo P, van der Schrier R, Burkhart K, Shah A, Racz R, Patel V, DePalma R, Matta M, Vegesna G, Hsiao CH, Rouse R, Fein M, Stone M, Dahan A, Strauss DG. Effect of Paroxetine or Escitalopram Coadministered with Oxycodone versus Oxycodone Alone on Ventilation during Hypercapnia: A Randomized Clinical Trial. Anesthesiology. 2026 Jul 1;145(1):98-110. doi: 10.1097/ALN.0000000000006043. Epub 2026 Mar 18.
PubMed 41849255
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study to Investigate the Effect of Administration of Selective Serotonin Reuptake Inhibitors (SSRIs) and an Opioid on Ventilation
- ClinicalTrials.gov ID
- NCT05470465
- Acronym / sponsor ID
- SCR-012
- Conditions
- Hypercapnia, Ventilatory Depression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Food and Drug Administration (FDA)US federal agency
- Collaborators
- Spaulding Clinical Research LLC, Leiden University
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 17 Sep 2023 (actual)
- Study completion
- 17 Sep 2023 (actual)
- First posted
- 22 Jul 2022 (actual)
- Results
- Posted 22 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate the effects of the coadministration of paroxetine or escitalopram with an opioid on ventilation. Ventilation will be assessed using a rebreathing methodology. This study will evaluate chronic and acute dosing of paroxetine and escitalopram combined with an opioid as well as chronic and acute dosing of the two drugs without coadministration of an opioid.
This study is a 3-period, randomized, placebo-controlled crossover study conducted with 25 healthy participants. Each participant will receive each of the 3 treatments (placebo/oxycodone, paroxetine/oxycodone, escitalopram/oxycodone) in a randomized order.
Detailed description
This study is designed to evaluate the effects of the coadministration of paroxetine or escitalopram, two selective serotonin reuptake inhibitors (SSRI), with an opioid on hypercapnic ventilation. Hypercapnic ventilation will be assessed under both hyperoxic and hypoxic conditions using the Duffin rebreathing method. This method allows for critical physiological measurements and thresholds to be captured that can then be used to model the effects of drugs when there are dynamic changes in oxygen partial pressure (PO2) and carbon dioxide partial pressure (PCO2), such as during a real-world opioid overdose.
SSRIs take approximately 3 weeks to reach maximal therapeutic effect, which correlates with the time required for pre-synaptic inhibitory serotonergic receptors to desensitize. Therefore, drug-effects on ventilation should be evaluated under steady state conditions.
This study is randomized, placebo-controlled crossover study which includes three 21-day periods conducted with 25 healthy participants. Participants will receive each of the 3 treatments (placebo/oxycodone, paroxetine/oxycodone, or escitalopram/oxycodone) in a randomized order. Paroxetine dosing will range from 40-60 mg once daily (QD) and escitalopram dosing will range from 20-30 mg QD. Subjects will receive 10 mg oxycodone on three different days each period. Subjects will undergo 6 days of rebreathing and time-matched pupillary assessments along with 3 separate days of ECG assessments each period. Additionally, blood samples will be collected for determination of plasma concentrations for each study drug on days with rebreathing and ECG assessments.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- This is a 3-period, double-blind, randomized crossover study. The duration of each treatment period will be 21 days in addition to a three-week washout between periods. The duration of study participation will be 106 days (excluding the screening period).
| Arm | Type | Receives |
|---|---|---|
| Treatment A: Placebo | Placebo comparator | Drug: Placebo and OxycodoneParticipants will receive placebo on days 1-21 for this treatment period. Oxycodone will be administered on days 6, 12, and 21 of this treatment period. |
| Treatment B: Paroxetine | Experimental | Drug: Paroxetine and OxycodoneParticipants will receive paroxetine on days 1-21 for this treatment period. Oxycodone will be administered on days 6, 12, and 21 of this treatment period. |
| Treatment C: Escitalopram | Experimental | Drug: Escitalopram and OxycodoneParticipants will receive escitalopram on days 1-21 for this treatment period. Oxycodone will be administered on days 6, 12, and 21 of this treatment period. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Subject signs an Institutional Review Board (IRB) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
- Subject is a healthy, non-smoking man or woman, 18 to 50 years of age, inclusive, who has a body mass index of 18.5 to 33.0 kg/m2, inclusive, at Screening.
- Subject has normal medical history findings, clinical laboratory results, vital sign measurements, pulse oximetry, 12-lead ECG results, and physical examination findings at screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
- Subject must have a negative test result for alcohol and drugs of abuse at screening and check-in days.
- Subject must test negative for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) by a rapid antigen test at check-in for all study periods. If a subject's test comes back as invalid, the test can be repeated.
Key exclusion criteria (31 listed)
- Subject has used any prescription or nonprescription drugs (including aspirin or NSAIDs and excluding oral contraceptives and acetaminophen) within 14 days or 5 half-lives (whichever is longer) or complementary and alternative medicines within 28 days before the first dose of study drug. This includes prescription or nonprescription ophthalmic drugs.
- Subject is currently participating in another clinical study of an investigational drug or has been treated with any investigational drug within 30 days or 5 half-lives (whichever is longer) of the compound.
- Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, electronic cigarettes) within 6 weeks of Screening. Subjects must refrain from using these throughout the study.
- Subject has consumed alcohol, xanthine containing products (e.g., tea, coffee, cola), caffeine, grapefruit, or grapefruit juice within 24 h of check-in. Subjects must refrain from ingesting these throughout the study.
- Subject has a history or evidence of a clinically significant disorder, condition, or disease (e.g., cancer, human immunodeficiency virus [HIV], hepatic or renal impairment) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. This includes subjects with any underlying medical conditions that put subjects at increased risk of severe illness from coronavirus disease 2019 (COVID-19) based on the Centers for Disease Control and Prevention (CDC) guidelines.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo and OxycodoneParticipants will receive placebo on days 1-21 for this treatment period. Oxycodone 10 mg (2 x 5 mg tablets) will be administered on days 6, 12, and 21 of this treatment period. | Drug | Treatment A: Placebo |
| Paroxetine and OxycodoneParticipants will receive 40 mg paroxetine (2 x 20 mg tablets) on days 1-6 and 60 mg paroxetine (3 x 20 mg tablets) on days 7-21 for this treatment period. Oxycodone 10 mg (2 x 5 mg tablets) will be administered on days 6, 12, and 21 of this treatment period. | Drug | Treatment B: Paroxetine |
| Escitalopram and OxycodoneParticipants will receive 20 mg escitalopram (2 x 10 mg tablets) on days 1-6 and 30 mg escitalopram (3 x 10 mg tablets) on days 7-21 for this treatment period. Oxycodone 10 mg (2 x 5 mg tablets) will be administered on days 6, 12, and 21 of this treatment period. | Drug | Treatment C: Escitalopram |
Primary outcome
Minute Ventilation at 55mm Hg End Tidal CO2 (VE55) Under Hyperoxic Conditions on Day 21
Time frame: 5 hours on day 21
Comparison of escitalopram or paroxetine with oxycodone to oxycodone alone. Rebreathing data will be analyzed by regression of the minute ventilation versus partial pressure of end tidal CO2 (PETCO2) data to estimate VE55. Resulting VE55 data will be compared using a linear mixed effects model. Comparison will be at 5 hours on day 21.
VE55 Under Hyperoxic Conditions on Day 20
Time frame: 5 hours on day 20
Comparison of escitalopram or paroxetine to placebo. Rebreathing data will be analyzed by regression of the minute ventilation versus partial pressure of end tidal CO2 (PETCO2) data to estimate VE55. Resulting VE55 data will be compared using a linear mixed effects model. Comparison will be at 5 hours on day 20.
4 secondary outcomes
VE55 Under Hyperoxic Conditions on Day 6
Time frame: 5 hours on day 6
VE55 Under Hyperoxic Conditions on Day 12
Time frame: 5 hours on day 12
VE55 Under Hyperoxic Conditions on Day 5
Time frame: 5 hours on day 5
VE55 Under Hyperoxic Conditions on Day 11
Time frame: 5 hours on day 11
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 34080766Xu 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.
- Background: PubMed 939123Rebuck AS. Measurement of ventilatory response to CO2 by rebreathing. Chest. 1976 Jul;70(1 Suppl):118-21. doi: 10.1378/chest.70.1_supplement.118. No abstract available.
- Background: PubMed 29029015van der Schrier R, Jonkman K, van Velzen M, Olofsen E, Drewes AM, Dahan A, Niesters M. An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers. Br J Anaesth. 2017 Dec 1;119(6):1169-1177. doi: 10.1093/bja/aex295.
- Background: PubMed 28170358van 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.
- Background: PubMed 10523062Nutt DJ, Forshall S, Bell C, Rich A, Sandford J, Nash J, Argyropoulos S. Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders. Eur Neuropsychopharmacol. 1999 Jul;9 Suppl 3:S81-6. doi: 10.1016/s0924-977x(99)00030-9.
- Background: PubMed 10997729Czachura JF, Rasmussen K. Effects of acute and chronic administration of fluoxetine on the activity of serotonergic neurons in the dorsal raphe nucleus of the rat. Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):266-75. doi: 10.1007/s002100000290.
- Background: PubMed 3116207Casey K, Duffin J, McAvoy GV. The effect of exercise on the central-chemoreceptor threshold in man. J Physiol. 1987 Feb;383:9-18. doi: 10.1113/jphysiol.1987.sp016392.
- Background: PubMed 3151077Duffin J, McAvoy GV. The peripheral-chemoreceptor threshold to carbon dioxide in man. J Physiol. 1988 Dec;406:15-26. doi: 10.1113/jphysiol.1988.sp017365.
- Background: PubMed 32673158Dong TW, MacLeod DB, Santoro A, Augustine Z, Barth S, Cooter M, Moon RE. A methodology to explore ventilatory chemosensitivity and opioid-induced respiratory depression risk. J Appl Physiol (1985). 2020 Sep 1;129(3):500-507. doi: 10.1152/japplphysiol.00460.2020. Epub 2020 Jul 16.
- Background: PubMed 6032026Read DJ. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med. 1967 Feb;16(1):20-32. doi: 10.1111/imj.1967.16.1.20. No abstract available.
- Background: PubMed 9386849Gorman JM, Browne ST, Papp LA, Martinez J, Welkowitz L, Coplan JD, Goetz RR, Kent J, Klein DF. Effect of antipanic treatment on response to carbon dioxide. Biol Psychiatry. 1997 Dec 1;42(11):982-91. doi: 10.1016/s0006-3223(97)00160-1.
- Background: PubMed 10950471Bertani A, Perna G, Arancio C, Caldirola D, Bellodi L. Pharmacologic effect of imipramine, paroxetine, and sertraline on 35% carbon dioxide hypersensitivity in panic patients: a double-blind, random, placebo-controlled study. J Clin Psychopharmacol. 1997 Apr;17(2):97-101. doi: 10.1097/00004714-199704000-00006.
Related trials for Hypercapnia
Active, not recruiting
Influence of FreeO2 on Percentage of Time Within Oxygen Saturation Target Using Noninvasive Ventilation (NIV) and Continuous Positive Airway Pressure (CPAP) for Patients Admitted for AECOPD or Bariatric Surgery
COPD Exacerbation, Oxygen Toxicity
RecruitingObservational study
Frequency and Severity of Respiratory Acidosis During One-lung Ventilation, a Retrospective Pilot Study to Compare Clinician Settings and Those Proposed by the VentilO Application
Thoracic, Surgery
Not yet recruiting
ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
Acute Respiratory Failure, Critical Illness
Not yet recruitingObservational study
Effectiveness and Efficiency of Home Telemonitoring and Non-invasive Ventilation in Patients With COPD and Hypercapnia (EVALECO)
Pulmonary Disease, Chronic Obstructive (COPD), Hypercapnia
Not yet recruiting
Comparing Two Types of Breathing Support in People With COPD, High Carbon Dioxide Levels, and Sleep Apnea
OSA COPD Overlap Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Matousek, D.O. principal investigator
Spaulding Clinical Research LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Paroxetine and Oxycodone and Escitalopram and Oxycodone in people with Hypercapnia and Ventilatory Depression, run by Food and Drug Administration (FDA) 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 8 inclusion and 31 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: finished, as of the sponsor's last update on 22 May 2025. 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?
Yes. Results are posted in the registry (first posted 22 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Minute Ventilation at 55mm Hg End Tidal CO2 (VE55) Under Hyperoxic Conditions on Day 21 (time frame: 5 hours on day 21). The study lists 2 primary outcomes in all. 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 NCT05470465, which also lists 14 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 22 May 2025.