Status:

COMPLETED

Clinical Study to Investigate the Effect of the Combination of Psychotropic Drugs and an Opioid on Ventilation

Lead Sponsor:

Food and Drug Administration (FDA)

Collaborating Sponsors:

Spaulding Clinical Research LLC

Leiden University

Conditions:

Hypercapnia

Ventilatory Depression

Eligibility:

All Genders

18-50 years

Phase:

PHASE1

Brief Summary

Opioids can decrease breathing and co-administration of benzodiazepines with opioids can further decrease breathing. It is unknown whether certain other drugs also decrease breathing when co-administe...

Detailed Description

Opioids can cause respiratory/ventilatory depression, and this can be exacerbated when opioids are co-administered with benzodiazepines. Research suggests this is caused by a reduced respiratory/venti...

Eligibility Criteria

Inclusion

  • 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 man or woman, 18 to 50 years of age, inclusive, who has a body mass index of 18.5 to 29.9 kg/m2, inclusive, at Screening.
  • Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead electrocardiogram (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 (Day -1).
  • Subject has no known or suspected allergies or sensitivities to any of the study drugs.
  • Female subjects must be of non-childbearing potential 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 1 month 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 last application of study drug.
  • Male subjects must agree to practice 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 last application of study drug.
  • Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures and to complete the study

Exclusion

  • Subject has history of opioid or psychotropic drug use within 60 days of the start of the study.
  • 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 intubation score of \>2 (for Part 1 and 2 only).
  • Subject Read Rebreathing data is of poor quality or subject does not agree to remain clean-shaven for all days when the Read Rebreathing procedure is being performed.
  • Subject has used any prescription or nonprescription drugs (including aspirin or \[non-steroidal anti-inflammatory drugs\] 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.
  • Subjects are currently participating in another clinical study of an investigational drug or are have 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) within 6 weeks of Screening.
  • Subject has consumed alcohol, xanthine containing products (e.g., tea, coffee, chocolate, cola), caffeine, grapefruit, or grapefruit juice within 48 h of dosing. Subjects must refrain from ingesting these throughout the study.
  • Subject has a history of sleep disorders, Panic Disorder, Panic Attacks, Generalized Anxiety Disorder, or any associated Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis or condition.
  • Subject has any underlying disease or surgical or medical condition (e.g., cancer, human immunodeficiency virus \[HIV\], severe hepatic or renal impairment) that could put the subject at risk or would normally prevent participation in a clinical study. This includes subjects with any underlying medical conditions that the Investigator believes would put subjects at increased risk of severe illness from COVID-19 based on the Centers for Disease Control and Prevention (CDC) guidelines. The CDC lists cancer, chronic kidney disease, chronic obstructive pulmonary disease, immunocompromised state from solid organ transplant, severe obesity, serious heart conditions, sickle cell disease, pregnancy, smoking and type 2 diabetes mellitus as conditions that put subjects at increased risk. Additionally, the CDC lists asthma (moderate-to-severe), cerebrovascular disease, cystic fibrosis, hypertension, immunocompromised state or immune deficiencies, neurologic conditions such as dementia, liver disease, pulmonary fibrosis, thalassemia, overweight, type 1 diabetes mellitus as conditions that might put subjects at increased risk.
  • Subject has any signs or symptoms that are consistent with COVID-19 per CDC recommendations. These include subjects with fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea may have COVID-19. In addition, the subject has any other findings suggestive of COVID-19 risk in the opinion of the investigator.
  • Subject tests positive for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) by a molecular diagnostic test performed prior to admission.
  • Female subject is pregnant or lactating before enrollment in the study.
  • Subject has known or suspected allergies or sensitivities to any study drug.
  • Subject has clinical laboratory test results (hematology, serum chemistry) at Screening that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator.
  • 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.
  • Subject has a history of or currently has hypoventilation syndrome or sleep apnea and is on non-invasive ventilation.

Key Trial Info

Start Date :

June 15 2020

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

May 25 2021

Estimated Enrollment :

55 Patients enrolled

Trial Details

Trial ID

NCT04310579

Start Date

June 15 2020

End Date

May 25 2021

Last Update

May 21 2024

Active Locations (1)

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Spaulding Clinical Research

West Bend, Wisconsin, United States, 53095