Drug Interaction, Analgesics, Opioid Use Disorder
Conditions
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.
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. S. Food and Drug Administration (FDA) for treatment of insomnia. In this study, Participants will be asked to do the following things: 1. Visit the CARI clinic and/or Motivate clinic at Jackson Center to complete study screening. 2. Visit the VCUHS Clinical Research Unit to complete an outpatient blood draw/testing visit. 3. Take either lemborexant or the placebo, depending upon which group subjects are assigned to. 4. Complete two (2) overnight study visits at the VCUHS Clinical Research Unit. 5. Complete 8 outpatient follow-up visits (broken into 2 four day visit groupings) 6. Have an EKG during screening and at each study visit (outpatient and inpatient) 7. Have an IV inserted into your arm for blood draws at the outpatient blood draw visit and each inpatient visit. 8. Record sleep in a sleep diary. 9. Take surveys and answer questions about health, mental health, medications used, drug use, and cravings. 10. Complete tasks on the computer. 11. Complete physical exams during screening, outpatient and inpatient visits. 12. 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.
Interventions
DRUGLemborexant
Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit).
DRUGPlacebo
Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which is encapsulated to look the same as the intervention drug.
Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Sponsors
National Institute on Drug Abuse (NIDA)
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females between 18 - 65 years-of-age; 2. Understand the study procedures and provide written informed consent in English language; 3. 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; 4. Have a positive urine drug screen for buprenorphine during screening and on admission to the clinical research unit to document buprenorphine use; 5. Have a Pittsburgh Sleep Quality Index (PSQI) Total Score of 6 or higher.
Exclusion criteria
1. Contraindications for participation as determined by medical history and physical exam performed by study NP or study physician; 2. Pregnant or nursing women; 3. Baseline ECG with clinically significant abnormal conduction; 4. Uncontrolled serious psychiatric or major medical disorder, including COPD. Narcolepsy is also considered exclusionary; 5. 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); 6. Prescribed medications for insomnia, or unable to discontinue over the counter drugs or dietary supplements used to treat insomnia on study days. 7. Current severe alcohol use disorder or current benzodiazepine use disorder 8. 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. 9. Any previous medically adverse reaction to opioids or lemborexant: 10. 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. 11. Subjects with Suicidal Behaviors Questionnaire-Revised score ≥8 at the screening visit. 12. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Respiration During Week 2 Study Visit (From Pre- to Post-dose) | Week 2 visit | Respiration will be measured 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. |
| Change in Patient Consciousness During the Baseline Visit | Baseline visit, safety measure | The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale ranging from plus +4 (combative/agitated) to minus 5 (unarousable/sedated). Change is calculated from the RASS assessment scores obtained from pre to post medication/placebo dose administered during the study visit. This is a safety measure. RASS is one of the most commonly used scales to determine the sedation level, and it measures the severity of agitation and sedation with a score of +4 to -5: +4: combative, +3: very agitated, +2: agitated, +1: restless, 0: alert and calm, -1: drowsy, -2: light sedation, -3: moderate sedation, -4: deep sedation, and -5 unarousable. A positive score is preferable to a negative score. |
| Change in Patient Consciousness During the Week 1 Study Visit | Week 1 visit, safety measure | The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale ranging from plus 4 (combative/agitated) to minus 5 (unarousable/sedated).Change is calculated from the RASS assessment scores obtained from pre to post medication/placebo dose administered during the study visit. This is a safety measure. RASS is one of the most commonly used scales to determine the sedation level, and it measures the severity of agitation and sedation with a score of +4 to -5: +4: combative, +3: very agitated, +2: agitated, +1: restless, 0: alert and calm, -1: drowsy, -2: light sedation, -3: moderate sedation, -4: deep sedation, and -5 unarousable. A positive score is preferable to a negative score. |
| Change in Patient Consciousness | Week 2 visit, safety measure | The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale ranging from plus 4 (combative/agitated) to minus 5 (unarousable/sedated). Change is calculated from the RASS assessment scores obtained from pre to post medication/placebo dose administered during the study visit. This is a safety measure. RASS is one of the most commonly used scales to determine the sedation level, and it measures the severity of agitation and sedation with a score of +4 to -5: +4: combative, +3: very agitated, +2: agitated, +1: restless, 0: alert and calm, -1: drowsy, -2: light sedation, -3: moderate sedation, -4: deep sedation, and -5 unarousable. A positive score is preferable to a negative score. |
| Change in Buprenorphine Plasma Concentration (PK) During the Baseline Visit | Baseline visit | Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for buprenorphine. |
| Change in Buprenorphine Plasma Concentration (PK) During Week 1 Study Visit | Week 1 | Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for buprenorphine. |
| Change in Buprenorphine Plasma Concentration (PK) During Week 2 Study Visit | Week 2 | Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for buprenorphine. |
| Change in Lemborexant PK During Baseline Study Visit | Baseline visit | Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the peak plasma concentration for Lemborexant. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do. |
| Change in Lemborexant PK During Week 1 Study Visit | Week 1 visit | Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for Lemborexant. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do. |
| Change in Lemborexant PK During Week 2 Study Visit | Week 2 visit | Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the peak plasma concentration for Lemborexant. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do. |
| Change in Respiration During the Baseline Study Visit (Pre- to Post-dose) | Baseline visit | Respiration will be measured 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. |
| Change in Respiration During the Week 1 Study Visit (Pre- to Post-dose) | Week 1 visit | Respiration will be measured 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 |
| Change in Pulse Oximetry During the Baseline Visit | Baseline visit (Safety measure) | A finger pulse oximeter will be used to assess oxygen saturation (%). Change is calculated from the pulse oximetry readings from pre to post medication/placebo dose administered during the baseline study visit, this is a safety measure. |
| Change in Pulse Oximetry During Week 1 Visit | Week 1 visit, safety measure | A finger pulse oximeter will be used to asses pulse oximetry. Change is calculated from the pulse oximetry readings from pre to post medication/placebo dose administered during the study visit (safety measure) |
| Change in Pulse Oximetry During Week 2 Visit | Week 2 visit, safety measure | A finger pulse oximeter will be used to assess pulse oximetry. Change is calculated from the pulse oximetry readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure. |
| Change in Blood Pressure During Baseline Study Visit | Baseline Visit, safety measure | Blood Pressure measured with an automatic BP cuff. Change is calculated from the blood pressure readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure. |
| Change in Blood Pressure During Week 1 Study Visit | Week 1 visit, safety measure | Blood Pressure measured with an automatic BP cuff. Change is calculated from the blood pressure readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure. |
| Change in Blood Pressure During Week 2 Study Visit | Week 2 visit, safety measure | Blood Pressure measured with an automatic BP cuff. Change is calculated from the blood pressure readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Drug Effects During Week 1 Study Visit (Pre- to Post- Dose) | Week 1 visit | 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 (0) to extremely (100). A higher score indicates greater drug effect. The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances and assesses the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales. |
| Change in Drug Effects During Week 2 Study Visit (Pre- to Post Dose) | Week 2 visit | 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 (0) to extremely (100). A higher score indicates greater drug effect. The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances and assesses the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales. |
| Change in Opioid Craving During Each Visit (Pre- to Post- Dose) | During each inpatient visit (baseline through week 2) from admission to discharge at each visit, up to 24 hours | Opioid craving will be measured by a Brief Substance craving scale (BSCS). The BSCS is a 16 item, self-report instrument assesses craving for substances of abuse over a 24 hour period. Intensity and frequency of craving are recorded on a five-point Likert scale, with higher scores indicating greater craving. 0-none at all, 1- slight, 2-moderate, 3-considerable, 4-extreme. |
| Change in Opioid Withdrawal Effects During Baseline Visit (Pre- to Post- Dose) | Baseline visit | 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), 1(slight), 2 (moderate), 3 (considerable) to 4 (Extreme). A higher score indicates higher opioid withdrawal effects (Range 0-64). |
| Change in Opioid Withdrawal Effects During Week 1 Visit (Pre- to Post- Dose) | Week 1 visit | 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), 1(slight), 2 (moderate), 3 (considerable) to 4 (Extremely). A higher score indicates higher opioid withdrawal effects(Range 0-64). |
| Change in Opioid Withdrawal Effects During Week 2 Visit (Pre- to Post- Dose) | Week 2 visit | 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), 1(slight), 2 (moderate), 3 (considerable) to 4 (Extremely). A higher score indicates higher opioid withdrawal effects (Range 0-64). |
| Change in Objective Opioid Withdrawal During Baseline Study Visit (Pre- to Post- Dose) | Baseline visit | 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. (COWS, range 0-48). 5-12=mild, 13-24=moderate, 25-36=moderate severe, and more than 36=severe withdrawal. |
| Change in Objective Opioid Withdrawal During Week 1 Study Visit (Pre- to Post-dose) | Week 1 visit | 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(COWS, range 0-48). 5-12=mild, 13-24=moderate, 25-36=moderate severe, and more than 36=severe withdrawal. |
| Change in Objective Opioid Withdrawal During Week 2 Study Visit (Pre- to Post- Dose) | Week 2 visit | 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 (COWS, range 0-48). 5-12=mild, 13-24=moderate, 25-36=moderate severe, and more than 36=severe withdrawal. |
| Impulsivity | Baseline visit | 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 greater impulsivity. Delay discounting, the tendency to choose small, immediate rewards over larger, delayed rewards is robustly associated with substance use. The longer the timeframe that the subject delays the rewards, the larger the reward. |
| Change in Drug Effects During Baseline Study Visit (Pre- to Post- Dose) | Baseline visit | 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 (0) to extremely (100). A higher score indicates greater drug effect. The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances and assesses the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lemborexant Arm Study Drug Dosage: 5 mg of lemborexant (Time 1) , and 10 mg of lemborexant (Time 2) combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film.
Lemborexant: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive 5 mg of lemborexant (first visit) and 10 mg of lemborexant (second visit).
Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. | 12 |
| Placebo Arm Comparative placebo combined with 16 mg/4 mg of buprenorphine-naloxone sublingually as a film (at both Time 1 and Time 2)
Placebo: Participants will complete 2 inpatient visits which may last up to 24 hours. The two visits will be approximately 14 days apart. During the inpatient visit they will receive a placebo which matches the intervention drug.
Buprenorphine-naloxone: Participants will receive 16 mg/4 mg of buprenorphine-naloxone sublingually as a film. | 6 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Lemborexant Arm | Total | Placebo Arm |
|---|---|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 7.3 | 39.6 years STANDARD_DEVIATION 10.2 | 44.3 years STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 17 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 11 Participants | 2 Participants |
| Region of Enrollment United States | 12 participants | 18 participants | 6 participants |
| Sex: Female, Male Female | 4 Participants | 10 Participants | 6 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 6 |
| other Total, other adverse events | 6 / 12 | 4 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 |
Outcome results
Primary
Change in Blood Pressure During Baseline Study Visit
Blood Pressure measured with an automatic BP cuff. Change is calculated from the blood pressure readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure.
Time frame: Baseline Visit, safety measure
Population: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Blood Pressure During Baseline Study Visit | -9.42 mmHg (millimeters of mercury) | Standard Deviation 10.4 |
| Placebo Arm | Change in Blood Pressure During Baseline Study Visit | -2.50 mmHg (millimeters of mercury) | Standard Deviation 12.29 |
Primary
Change in Blood Pressure During Week 1 Study Visit
Blood Pressure measured with an automatic BP cuff. Change is calculated from the blood pressure readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure.
Time frame: Week 1 visit, safety measure
Population: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Blood Pressure During Week 1 Study Visit | -6.58 mmHg (millimeters of mercury) | Standard Deviation 6.64 |
| Placebo Arm | Change in Blood Pressure During Week 1 Study Visit | -4.50 mmHg (millimeters of mercury) | Standard Deviation 5.68 |
Primary
Change in Blood Pressure During Week 2 Study Visit
Blood Pressure measured with an automatic BP cuff. Change is calculated from the blood pressure readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure.
Time frame: Week 2 visit, safety measure
Population: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Blood Pressure During Week 2 Study Visit | 1.09 mmHg (millimeters of mercury) | Standard Deviation 12.85 |
| Placebo Arm | Change in Blood Pressure During Week 2 Study Visit | -3.60 mmHg (millimeters of mercury) | Standard Deviation 8.53 |
Primary
Change in Buprenorphine Plasma Concentration (PK) During the Baseline Visit
Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for buprenorphine.
Time frame: Baseline visit
Population: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Buprenorphine Plasma Concentration (PK) During the Baseline Visit | 0.26 Nanograms/milliliter (ng/mL) | Standard Deviation 0.29 |
Primary
Change in Buprenorphine Plasma Concentration (PK) During Week 1 Study Visit
Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for buprenorphine.
Time frame: Week 1
Population: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Buprenorphine Plasma Concentration (PK) During Week 1 Study Visit | 0.15 Nanograms/milliliter (ng/mL) | Standard Deviation 0.18 |
Primary
Change in Buprenorphine Plasma Concentration (PK) During Week 2 Study Visit
Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for buprenorphine.
Time frame: Week 2
Population: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Buprenorphine Plasma Concentration (PK) During Week 2 Study Visit | 0.12 Nanograms/milliliter (ng/mL) | Standard Deviation 0.18 |
Primary
Change in Lemborexant PK During Baseline Study Visit
Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the peak plasma concentration for Lemborexant. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.
Time frame: Baseline visit
Population: Lemborexant serum levels are not provided as the detailed methods for lemborexant level determination are proprietary and we do not have access to those methods. Hence, we are not able to provide the lemborexant levels. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.
Primary
Change in Lemborexant PK During Week 1 Study Visit
Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the area under the plasma concentration-time curve for Lemborexant. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.
Time frame: Week 1 visit
Population: Lemborexant serum levels are not provided as the detailed methods for lemborexant level determination are proprietary and we do not have access to those methods. Hence, we are not able to provide the lemborexant levels. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.
Primary
Change in Lemborexant PK During Week 2 Study Visit
Blood will be drawn pre-dose and at specific time points (8, 8:30, 10, 12 and 4pm) to determine the peak plasma concentration for Lemborexant. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.
Time frame: Week 2 visit
Population: Lemborexant serum levels are not provided as the detailed methods for lemborexant level determination are proprietary and we do not have access to those methods. Hence, we are not able to provide the lemborexant levels. Currently, we have no pathway to obtain the lorcaserin PK results. The reason for that is the methods used for the original lorcaserin human PK testing are proprietary and we would have to re-do all of that research ourselves, which is outside the scope of what we are able to do.
Primary
Change in Patient Consciousness
The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale ranging from plus 4 (combative/agitated) to minus 5 (unarousable/sedated). Change is calculated from the RASS assessment scores obtained from pre to post medication/placebo dose administered during the study visit. This is a safety measure. RASS is one of the most commonly used scales to determine the sedation level, and it measures the severity of agitation and sedation with a score of +4 to -5: +4: combative, +3: very agitated, +2: agitated, +1: restless, 0: alert and calm, -1: drowsy, -2: light sedation, -3: moderate sedation, -4: deep sedation, and -5 unarousable. A positive score is preferable to a negative score.
Time frame: Week 2 visit, safety measure
Population: week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Patient Consciousness | -0.18 score on a scale | Standard Deviation 0.87 |
| Placebo Arm | Change in Patient Consciousness | -0.20 score on a scale | Standard Deviation 0.45 |
Primary
Change in Patient Consciousness During the Baseline Visit
The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale ranging from plus +4 (combative/agitated) to minus 5 (unarousable/sedated). Change is calculated from the RASS assessment scores obtained from pre to post medication/placebo dose administered during the study visit. This is a safety measure. RASS is one of the most commonly used scales to determine the sedation level, and it measures the severity of agitation and sedation with a score of +4 to -5: +4: combative, +3: very agitated, +2: agitated, +1: restless, 0: alert and calm, -1: drowsy, -2: light sedation, -3: moderate sedation, -4: deep sedation, and -5 unarousable. A positive score is preferable to a negative score.
Time frame: Baseline visit, safety measure
Population: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Patient Consciousness During the Baseline Visit | -0.17 score on a scale | Standard Deviation 0.39 |
| Placebo Arm | Change in Patient Consciousness During the Baseline Visit | 0 score on a scale | Standard Deviation 0.63 |
Primary
Change in Patient Consciousness During the Week 1 Study Visit
The Richmond Agitation Sedation Scale (RASS) measures level of patient consciousness on a 10 point scale ranging from plus 4 (combative/agitated) to minus 5 (unarousable/sedated).Change is calculated from the RASS assessment scores obtained from pre to post medication/placebo dose administered during the study visit. This is a safety measure. RASS is one of the most commonly used scales to determine the sedation level, and it measures the severity of agitation and sedation with a score of +4 to -5: +4: combative, +3: very agitated, +2: agitated, +1: restless, 0: alert and calm, -1: drowsy, -2: light sedation, -3: moderate sedation, -4: deep sedation, and -5 unarousable. A positive score is preferable to a negative score.
Time frame: Week 1 visit, safety measure
Population: week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Patient Consciousness During the Week 1 Study Visit | 0.00 score on a scale | Standard Deviation 0.6 |
| Placebo Arm | Change in Patient Consciousness During the Week 1 Study Visit | 0.33 score on a scale | Standard Deviation 0.52 |
Primary
Change in Pulse Oximetry During the Baseline Visit
A finger pulse oximeter will be used to assess oxygen saturation (%). Change is calculated from the pulse oximetry readings from pre to post medication/placebo dose administered during the baseline study visit, this is a safety measure.
Time frame: Baseline visit (Safety measure)
Population: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Pulse Oximetry During the Baseline Visit | -0.17 percentage of oxygen saturation | Standard Deviation 0.94 |
| Placebo Arm | Change in Pulse Oximetry During the Baseline Visit | -0.33 percentage of oxygen saturation | Standard Deviation 0.82 |
Primary
Change in Pulse Oximetry During Week 1 Visit
A finger pulse oximeter will be used to asses pulse oximetry. Change is calculated from the pulse oximetry readings from pre to post medication/placebo dose administered during the study visit (safety measure)
Time frame: Week 1 visit, safety measure
Population: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Pulse Oximetry During Week 1 Visit | -0.17 percentage of oxygen saturation | Standard Deviation 1.94 |
| Placebo Arm | Change in Pulse Oximetry During Week 1 Visit | -0.50 percentage of oxygen saturation | Standard Deviation 1.05 |
Primary
Change in Pulse Oximetry During Week 2 Visit
A finger pulse oximeter will be used to assess pulse oximetry. Change is calculated from the pulse oximetry readings from pre to post medication/placebo dose administered during the study visit. This is a safety measure.
Time frame: Week 2 visit, safety measure
Population: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Pulse Oximetry During Week 2 Visit | -0.27 percentage of oxygen saturation | Standard Deviation 1.49 |
| Placebo Arm | Change in Pulse Oximetry During Week 2 Visit | -0.20 percentage of oxygen saturation | Standard Deviation 0.84 |
Primary
Change in Respiration During the Baseline Study Visit (Pre- to Post-dose)
Respiration will be measured 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.
Time frame: Baseline visit
Population: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Respiration During the Baseline Study Visit (Pre- to Post-dose) | 1.0 mmHg (millimeters of mercury) | Standard Deviation 4.18 |
| Placebo Arm | Change in Respiration During the Baseline Study Visit (Pre- to Post-dose) | 1.40 mmHg (millimeters of mercury) | Standard Deviation 3.65 |
Primary
Change in Respiration During the Week 1 Study Visit (Pre- to Post-dose)
Respiration will be measured 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
Time frame: Week 1 visit
Population: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Respiration During the Week 1 Study Visit (Pre- to Post-dose) | 1.67 millimeters of mercury (mmHg) | Standard Deviation 2.46 |
| Placebo Arm | Change in Respiration During the Week 1 Study Visit (Pre- to Post-dose) | 0.50 millimeters of mercury (mmHg) | Standard Deviation 8.8 |
Primary
Change in Respiration During Week 2 Study Visit (From Pre- to Post-dose)
Respiration will be measured 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.
Time frame: Week 2 visit
Population: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Respiration During Week 2 Study Visit (From Pre- to Post-dose) | 2.18 mmHg (millimeters of mercury) | Standard Deviation 3.28 |
| Placebo Arm | Change in Respiration During Week 2 Study Visit (From Pre- to Post-dose) | 1.60 mmHg (millimeters of mercury) | Standard Deviation 1.52 |
Secondary
Change in Drug Effects During Baseline Study Visit (Pre- to Post- Dose)
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 (0) to extremely (100). A higher score indicates greater drug effect. The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances and assesses the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales.
Time frame: Baseline visit
Population: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Drug Effects During Baseline Study Visit (Pre- to Post- Dose) | 21.0 score on a scale | Standard Deviation 39.95 |
| Placebo Arm | Change in Drug Effects During Baseline Study Visit (Pre- to Post- Dose) | 7.33 score on a scale | Standard Deviation 8.91 |
Secondary
Change in Drug Effects During Week 1 Study Visit (Pre- to Post- Dose)
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 (0) to extremely (100). A higher score indicates greater drug effect. The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances and assesses the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales.
Time frame: Week 1 visit
Population: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Drug Effects During Week 1 Study Visit (Pre- to Post- Dose) | 14.50 score on a scale | Standard Deviation 21.72 |
| Placebo Arm | Change in Drug Effects During Week 1 Study Visit (Pre- to Post- Dose) | 5.33 score on a scale | Standard Deviation 35.83 |
Secondary
Change in Drug Effects During Week 2 Study Visit (Pre- to Post Dose)
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 (0) to extremely (100). A higher score indicates greater drug effect. The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances and assesses the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales.
Time frame: Week 2 visit
Population: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Drug Effects During Week 2 Study Visit (Pre- to Post Dose) | 5.45 score on a scale | Standard Deviation 41.31 |
| Placebo Arm | Change in Drug Effects During Week 2 Study Visit (Pre- to Post Dose) | 18.00 score on a scale | Standard Deviation 32.27 |
Secondary
Change in Objective Opioid Withdrawal During Baseline Study Visit (Pre- to Post- Dose)
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. (COWS, range 0-48). 5-12=mild, 13-24=moderate, 25-36=moderate severe, and more than 36=severe withdrawal.
Time frame: Baseline visit
Population: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Objective Opioid Withdrawal During Baseline Study Visit (Pre- to Post- Dose) | -0.83 score on a scale | Standard Deviation 1.19 |
| Placebo Arm | Change in Objective Opioid Withdrawal During Baseline Study Visit (Pre- to Post- Dose) | -0.17 score on a scale | Standard Deviation 0.98 |
Secondary
Change in Objective Opioid Withdrawal During Week 1 Study Visit (Pre- to Post-dose)
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(COWS, range 0-48). 5-12=mild, 13-24=moderate, 25-36=moderate severe, and more than 36=severe withdrawal.
Time frame: Week 1 visit
Population: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Objective Opioid Withdrawal During Week 1 Study Visit (Pre- to Post-dose) | -0.50 score on a scale | Standard Deviation 1.09 |
| Placebo Arm | Change in Objective Opioid Withdrawal During Week 1 Study Visit (Pre- to Post-dose) | -0.17 score on a scale | Standard Deviation 0.41 |
Secondary
Change in Objective Opioid Withdrawal During Week 2 Study Visit (Pre- to Post- Dose)
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 (COWS, range 0-48). 5-12=mild, 13-24=moderate, 25-36=moderate severe, and more than 36=severe withdrawal.
Time frame: Week 2 visit
Population: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Objective Opioid Withdrawal During Week 2 Study Visit (Pre- to Post- Dose) | -0.27 score on a scale | Standard Deviation 1.27 |
| Placebo Arm | Change in Objective Opioid Withdrawal During Week 2 Study Visit (Pre- to Post- Dose) | 0 score on a scale | Standard Deviation 0 |
Secondary
Change in Opioid Craving During Each Visit (Pre- to Post- Dose)
Opioid craving will be measured by a Brief Substance craving scale (BSCS). The BSCS is a 16 item, self-report instrument assesses craving for substances of abuse over a 24 hour period. Intensity and frequency of craving are recorded on a five-point Likert scale, with higher scores indicating greater craving. 0-none at all, 1- slight, 2-moderate, 3-considerable, 4-extreme.
Time frame: During each inpatient visit (baseline through week 2) from admission to discharge at each visit, up to 24 hours
Population: During each inpatient visit from admission to discharge, up to 24 hours (Baseline through week 2)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Opioid Craving During Each Visit (Pre- to Post- Dose) | -025 score on a scale | Standard Deviation 2.09 |
| Placebo Arm | Change in Opioid Craving During Each Visit (Pre- to Post- Dose) | 3.0 score on a scale | Standard Deviation 8 |
Secondary
Change in Opioid Withdrawal Effects During Baseline Visit (Pre- to Post- Dose)
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), 1(slight), 2 (moderate), 3 (considerable) to 4 (Extreme). A higher score indicates higher opioid withdrawal effects (Range 0-64).
Time frame: Baseline visit
Population: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Opioid Withdrawal Effects During Baseline Visit (Pre- to Post- Dose) | -1.92 score on a scale | Standard Deviation 2.39 |
| Placebo Arm | Change in Opioid Withdrawal Effects During Baseline Visit (Pre- to Post- Dose) | -.033 score on a scale | Standard Deviation 0.52 |
Secondary
Change in Opioid Withdrawal Effects During Week 1 Visit (Pre- to Post- Dose)
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), 1(slight), 2 (moderate), 3 (considerable) to 4 (Extremely). A higher score indicates higher opioid withdrawal effects(Range 0-64).
Time frame: Week 1 visit
Population: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Opioid Withdrawal Effects During Week 1 Visit (Pre- to Post- Dose) | -0.25 score on a scale | Standard Deviation 0.97 |
| Placebo Arm | Change in Opioid Withdrawal Effects During Week 1 Visit (Pre- to Post- Dose) | -0.17 score on a scale | Standard Deviation 0.41 |
Secondary
Change in Opioid Withdrawal Effects During Week 2 Visit (Pre- to Post- Dose)
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), 1(slight), 2 (moderate), 3 (considerable) to 4 (Extremely). A higher score indicates higher opioid withdrawal effects (Range 0-64).
Time frame: Week 2 visit
Population: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Change in Opioid Withdrawal Effects During Week 2 Visit (Pre- to Post- Dose) | -0.45 score on a scale | Standard Deviation 0.93 |
| Placebo Arm | Change in Opioid Withdrawal Effects During Week 2 Visit (Pre- to Post- Dose) | 0 score on a scale | Standard Deviation 0 |
Secondary
Impulsivity
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 greater impulsivity. Delay discounting, the tendency to choose small, immediate rewards over larger, delayed rewards is robustly associated with substance use. The longer the timeframe that the subject delays the rewards, the larger the reward.
Time frame: Baseline visit
Population: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Impulsivity | 55.73 score on a scale | Standard Deviation 90.25 |
| Placebo Arm | Impulsivity | 74.74 score on a scale | Standard Deviation 51.31 |
Secondary
Impulsivity
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 greater impulsivity. Delay discounting, the tendency to choose small, immediate rewards over larger, delayed rewards is robustly associated with substance use. The longer the timeframe that the subject delays the rewards, the larger the reward.
Time frame: Week 1 visit
Population: Week 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Impulsivity | 6.51 score on a scale | Standard Deviation 76.73 |
| Placebo Arm | Impulsivity | 22.92 score on a scale | Standard Deviation 23.96 |
Secondary
Impulsivity
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 greater impulsivity. Delay discounting, the tendency to choose small, immediate rewards over larger, delayed rewards is robustly associated with substance use. The longer the timeframe that the subject delays the rewards, the larger the reward.
Time frame: Week 2 visit
Population: Week 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lemborexant Arm | Impulsivity | -40.63 score on a scale | Standard Deviation 126.27 |
| Placebo Arm | Impulsivity | -1.25 score on a scale | Standard Deviation 9.47 |