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| ID | Type | Description | Link |
|---|---|---|---|
| R01DA027031 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
| Merck Sharp & Dohme LLC | INDUSTRY |
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Addressing the issue of opioid dependence and tolerance has public health implications for the treatment of opioid abuse (both heroin as well as pharmaceutical opioids) and for the treatment of pain. Recent preclinical data suggest a role for Substance P (NK-1) receptors in modulating both the acute and chronic response to opioids. The objective of this study is to determine whether pretreatment with aprepitant, a selective neurokinin-1 (NK-1) antagonist can reduce the direct response to an opioid agonist (oxycodone) on measures related to abuse liability and reinforcing effects.
Healthy adult volunteers with histories of illicit opioid use by the intranasal and oral routes will be admitted to this 6-week inpatient, crossover study. They will participate in 15 experimental test sessions, each lasting approximately 6.5 hours, during which they will receive a range of acute doses of aprepitant, including placebo, followed by challenge with oxycodone or placebo (given intranasally or orally). Multi-dimensional outcomes, including physiological (blood pressure, oxygen saturation, pupil diameter), subjective (questionnaires related to mood, abuse liability) and observer ratings will be collected repeatedly throughout each session. Data will be analyzed using parametric approaches to within-subject designs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo aprepitant/0 mg oxycodone IN PO | Experimental | Placebo aprepitant/Placebo oxycodone IN/PO |
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| Placebo aprepitant/ oxycodone 15 IN 0 PO | Experimental | Placebo aprepitant/ oxycodone 15 IN 0 PO |
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| Placebo aprepitant/ oxycodone 30 IN 0 PO | Experimental | Placebo aprepitant/ oxycodone 30 IN 0 PO |
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| Placebo aprepitant/ oxycodone 0 IN 20 PO | Experimental | Placebo aprepitant/ oxycodone 0 IN 20 PO |
|
| Placebo aprepitant/ oxycodone 0 IN 40 PO | Experimental | Placebo aprepitant/ oxycodone 0 IN 40 PO |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aprepitant 0mg | Drug | Aprepitant 0mg, p.o. pretreatment |
|
| Measure | Description | Time Frame |
|---|---|---|
| Abuse Liability Proxy | Visual analog scale ratings (from 0-100) on the subject-rated measure of "How much do you like the drug?" with higher scores indicating greater abuse liability (and 100 anchored with "extremely" and zero indicating none anchored with "none at all." Data were collected across multiple time points but the peak maximum score was used for the primary outcome measure. | 42 days |
| Measure | Description | Time Frame |
|---|---|---|
| Respiration Depression | Respiration rate measured over 60 seconds. Data were collected across multiple time points, but the peak minimum score was used for this outcome measure. | 42 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sharon L Walsh, Ph.D. | University of Kentucky | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kentucky | Lexington | Kentucky | 40502 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22260216 | Result | Walsh SL, Heilig M, Nuzzo PA, Henderson P, Lofwall MR. Effects of the NK1 antagonist, aprepitant, on response to oral and intranasal oxycodone in prescription opioid abusers. Addict Biol. 2013 Mar;18(2):332-43. doi: 10.1111/j.1369-1600.2011.00419.x. Epub 2012 Jan 19. |
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Subjects were initially screened for inclusion/exclusion criteria. Fifteen subjects signed the screening consent but only nine were qualified to participate and signed the study consent. One subject left the study before receiving any interventions.
All recruitment was conducted through a research clinic at a public university.
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| ID | Title | Description |
|---|---|---|
| FG000 | Within-subject Crossover Design | All subjects received exposure to every study condition in random order. During each of 15 separate test sessions, subjects received pretreatment with aprepitant (0, 40 or 200 mg) followed by a single challenge with a oxycodone (15 or 30, intranasal; 20 or 40 mg) or placebo. The fifteen dose conditions were administered in random order and each subject was exposed to each dose combination once. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Crossover Within Subject | All subjects were exposed to every condition. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Abuse Liability Proxy | Visual analog scale ratings (from 0-100) on the subject-rated measure of "How much do you like the drug?" with higher scores indicating greater abuse liability (and 100 anchored with "extremely" and zero indicating none anchored with "none at all." Data were collected across multiple time points but the peak maximum score was used for the primary outcome measure. | Prior laboratory-based within subject studies of the pharmacodynamic response to opioid challenges. The within subject data analysis does not lend itself to reporting data in the format provided below. | Posted | Mean | Standard Deviation | units on a scale (points 0-100) | 42 days |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Within-subject Crossover Design | All subjects received exposure to every study condition in random order. This was not a parallel group design. |
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No significant adverse effects occurred. No adverse events led to study drop-out.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Sharon Walsh | University of Kentucky | 859-257-6485 | sharon.walsh@uky.edu |
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| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000077608 | Aprepitant |
| D010098 | Oxycodone |
| ID | Term |
|---|---|
| D009025 | Morpholines |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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Within subject crossover designed that examined 15 experimental conditions within a single group of participants
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| Aprepitant 40 mg/ oxycodone 0 IN 0 PO | Experimental | Aprepitant 40 mg/ oxycodone 0 IN 0 PO |
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| Aprepitant 40 mg/ oxycodone 0 IN 20 PO | Experimental | Aprepitant 40 mg/ oxycodone 0 IN 20 PO |
|
| Aprepitant 40 mg/ oxycodone 0 IN 40 PO | Experimental | Aprepitant 40 mg/ oxycodone 0 IN 40 PO |
|
| Aprepitant 40 mg/ oxycodone 15 IN 0 PO | Experimental | Aprepitant 40 mg/ oxycodone 15 IN 0 PO |
|
| Aprepitant 40 mg/ oxycodone 30 IN 0 PO | Experimental | Aprepitant 40 mg/ oxycodone 30 IN 0 PO |
|
| Aprepitant 200 mg/ oxycodone 0 IN 0 PO | Experimental | Aprepitant 200 mg/ oxycodone 0 IN 0 PO |
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| Aprepitant 200 mg/ oxycodone 0 IN 20 PO | Experimental | Aprepitant 200 mg/ oxycodone 0 IN 20 PO |
|
| Aprepitant 200 mg/ oxycodone 0 IN 40 PO | Experimental | Aprepitant 200 mg/ oxycodone 0 IN 40 PO |
|
| Aprepitant 200 mg/ oxycodone 15 IN 0 PO | Experimental | Aprepitant 200 mg/ oxycodone 15 IN 0 PO |
|
| Aprepitant 200 mg/ oxycodone 30 IN 0 PO | Experimental | Aprepitant 200 mg/ oxycodone 30 IN 0 PO |
|
| Aprepitant 40mg | Drug | Aprepitant 40mg, p.o. pretreatment |
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| Aprepitant 200mg | Drug | Aprepitant 200mg, p.o. pretreatment |
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| Oxycodone 0mg, p.o. | Drug | Oxycodone 0mg, p.o. |
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| Oxycodone 20mg, p.o. | Drug | Oxycodone 20mg, p.o. |
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| Oxycodone 40mg, p.o. | Drug | Oxycodone 40mg, p.o. |
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| Oxycodone 0mg, IN | Drug | Oxycodone 0mg, IN |
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| Oxycodone 15mg, IN | Drug | Oxycodone 15mg, IN |
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| Oxycodone 30mg, IN | Drug | Oxycodone 30mg, IN |
|
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Aprepitant 40 mg - Placebo |
All subjects received exposure to this study condition once. |
| OG002 | Aprepitant 200 mg- Placebo | All subjects received exposure to this study condition once. |
| OG003 | Placebo- 15 mg Oxycodone Intranasal | All subjects received exposure to this study condition once. |
| OG004 | Placebo- 30 mg Oxycodone Intranasal | All subjects received exposure to this study condition once. |
| OG005 | Placebo- 20 mg Oxycodone Oral | All subjects received exposure to this study condition once. |
| OG006 | Placebo - 40 mg Oxycodone Oral | All subjects received exposure to this study condition once. |
| OG007 | Aprepitant 40 mg- 15 mg Oxycodone Intranasal | All subjects received exposure to this study condition once. |
| OG008 | Aprepitant 40 mg - 30 mg Oxycodone Intranasal | All subjects received exposure to this study condition once. |
| OG009 | Aprepitant 40 mg- 20 mg Oxycodone Oral | All subjects received exposure to this study condition once. |
| OG010 | Aprepitant 40 mg - 40 mg Oxycodone Oral | All subjects received exposure to this study condition once. |
| OG011 | Aprepitant 200 mg - 15 mg Oxycodone Intranasal | All subjects received exposure to this study condition once. |
| OG012 | Aprepitant 200 mg - 30 mg Oxycodone Intranasal | All subjects received exposure to this study condition once. |
| OG013 | Aprepitant 200 mg- 20 Oxycodone Oral | All subjects received exposure to this study condition once. |
| OG014 | Aprepitant 200 mg- 40 Oxycodone Oral | All subjects received exposure to this study condition once. |
|
|
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| Secondary | Respiration Depression | Respiration rate measured over 60 seconds. Data were collected across multiple time points, but the peak minimum score was used for this outcome measure. | Prior laboratory-based within subject studies of the pharmacodynamic response to opioid challenges. | Posted | Mean | Standard Deviation | number of breaths per minute | 42 days |
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| 0 |
| 8 |
| 0 |
| 8 |
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| D003061 |
| Codeine |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |