Drug-drug Interaction Study of Lemborexant as an Adjunctive Treatment for Buprenorphine/Naloxone for Opioid Use Disorder
Study Details
Study Description
Brief Summary
The purpose of this research study is to test the safety, tolerability, drug interactions with buprenorphine-naloxone, and effectiveness lemborexant when used to treat Opioid Use Disorder.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The purpose of this study is to test the effects of lemborexant when used in combination with opioids (including buprenorphine). We are also interested in learning lemborexant might help improve sleep problems and problems related to opioid use (e.g., cravings, withdrawal), in people with opioid use disorder. Study participants will be randomly assigned in a two to one ratio to receive either lemborexant or placebo. Lemborexant (DAYVIGO®) is approved by the U.
- Food and Drug Administration (FDA) for treatment of insomnia.
In this study, Participants will be asked to do the following things:
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Visit the CARI clinic and/or Motivate clinic at Jackson Center to complete study screening.
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Visit the VCUHS Clinical Research Unit to complete an outpatient blood draw/testing visit.
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Take either lemborexant or the placebo, depending upon which group subjects are assigned to.
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Complete two (2) overnight study visits at the VCUHS Clinical Research Unit.
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Complete 8 outpatient follow-up visits (broken into 2 four day visit groupings)
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Have an EKG during screening and at each study visit (outpatient and inpatient)
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Have an IV inserted into your arm for blood draws at the outpatient blood draw visit and each inpatient visit.
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Record sleep in a sleep diary.
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Take surveys and answer questions about health, mental health, medications used, drug use, and cravings.
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Complete tasks on the computer.
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Complete physical exams during screening, outpatient and inpatient visits.
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Give permission for the researchers to collect information about opioid treatment, medical status, and other information from your medical record.
Participation in this study will last approximately 4 weeks. Approximately 18 people will participate in the drug interaction phase of this study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Lemborexant Arm Study Drug Dosage: 5 mg of lemborexant, and 10 mg of lemborexant, all subjects will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. |
Drug: Lemborexant
5 mg of lemborexant, and 10 mg of lemborexant, all subjects will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Other Names:
|
| Placebo Comparator: Placebo Arm Comparative placebo, all subjects will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. |
Drug: Placebo
Placebo tablet all subjects will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in pulse oximetry [Bbaseline to discharge, up to 24 hours]
A finger pulse oximeter will be used to asses pulse oximetry.
- Change in Blood Pressure [Baseline to discharge, up to 24 hours]
Blood Pressure measured with an automatic BP cuff.
- Change in patient consciousness [Change from baseline to discharge, up to 24 hours]
The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale raging from plus 1 (combative/agitated) to minus 5 (unarousable/sedated).
- Change in Buprenorphine Plasma Concentration (PK) [Baseline to discharge, up to 24 hours]
Blood will be drawn pre-dose and at specific time points to determine the area under the plasma concentration-time curve for buprenorphine.
- Change in Lemborexant PK [Baseline to discharge, up to 24 hours]
Blood will be drawn pre-dose and at specific time points to determine the area under the plasma concentration-time curve for Lemborexant.
- Change in respiration [Change from baseline to discharge, up to 24 hours]
Respiration will be measuring with End Title CO2( EtC02) which is a measure of CO2 (measured in millimeters of mercury, "mmHg") plotted against time. Participants will wear a mask which will be connected to a Capnographer. End Title CO2 should be between 35-45 mmHg with box wave form
Secondary Outcome Measures
- Change in drug effects [Baseline to discharge, up to 24 hours]
Drug effects will be assessed using the Drug Effects Questionnaire (DEQ). The DEQ is comprised of 11 items which assess physical effects of the drug. Participants rate each physical effect on a visual analog scale from "not at all" to "extremely." A higher score indicates greater drug effect.
- Change in opioid craving [Change from baseline to discharge, up to 24 hours]
Opioid craving will be measured by a Brief Substance craving scale (BSCS). The BSCS asks about the drug craving on a 5 point scale. A higher score indicates greater craving
- Change in opioid withdrawal effects [Baseline to discharge, up to 24 hours]
Opioid withdrawal symptoms will be measured with the Subjective Opioid Withdrawal Scale (SOWS). The SOWS contains 16 likert scaled items with participant rate from 0 (not at all) to 4 (Extremely). A higher score indicates higher opioid withdrawal effects
- Change in objective opioid withdrawal [Baseline to discharge, up to 24 hours]
Participants will be assessed by research staff using the Clinical Opioid Withdrawal Scale (COWS) which consists of 11 items. A higher score indicates greater withdrawal effects.
- Impulsivity [Baseline to discharge, up to 24 hours]
Impulsivity is measured by a delayed discounting task (DDT). Participants are presented with a series of choices and will choose to receive pretend money now or after a delay. The task yields a discounting rate. Higher discounting rates indicate higher impulsivity.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Males and females between 18 - 65 years-of-age;
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Understand the study procedures and provide written informed consent in English language;
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Meet current DSM-5 criteria for opioid use disorder, of at least moderate severity, currently engaged medication assisted treatment at a buprenorphine-naloxone sublingual film daily dose ranging from 8mg/2mg to 24mg/6mg or buprenorphine sublingual tablet 5.7mg/1.4mg to 17.1/4.3 once daily for at least last 2 weeks;
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Have a positive urine drug screen for buprenorphine during screening and on admission to the clinical research unit to document buprenorphine use;
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Have a Pittsburgh Sleep Quality Index (PSQI) Total Score of 6 or higher.
Exclusion Criteria:
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Contraindications for participation as determined by medical history and physical exam performed by study NP or study physician;
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Pregnant or nursing women;
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Baseline ECG with clinically significant abnormal conduction;
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Uncontrolled serious psychiatric or major medical disorder, including COPD. Narcolepsy is also considered exclusionary;
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Taking prescription or over-the counter drugs or dietary supplements known to significantly inhibit CYP3A4 (such as Clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir), or CYP3A4 inducers (such as phenobarbital, phenytoin, rifampicin, St. John's Wort, and glucocorticoids);
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Prescribed medications for insomnia, or unable to discontinue over the counter drugs or dietary supplements used to treat insomnia on study days.
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Current severe alcohol use disorder or current benzodiazepine use disorder
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Current DSM-5 diagnosis of any psychoactive substance use disorder other than opioids, cocaine, marijuana, or nicotine, or mild or moderate alcohol use disorder. Diagnosis of mild to moderate use disorder for alcohol will not be considered exclusionary.
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Any previous medically adverse reaction to opioids or lemborexant:
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Significant current suicidal or homicidal ideation (C-SSRS "yes" answers on questions 4 or 5) or a history of suicide attempt within the past 6 months.
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Subjects with Suicidal Behaviors Questionnaire-Revised score ≥8 at the screening visit.
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Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Virginia Commonwealth University | Richmond | Virginia | United States | 23298 |
Sponsors and Collaborators
- Virginia Commonwealth University
- National Institute on Drug Abuse (NIDA)
Investigators
- Principal Investigator: Frederick G Moeller, MD, Virginia Commonwealth University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HM20021136
- UG1DA050207