UH3: Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal
Study Details
Study Description
Brief Summary
A placebo-controlled trial in which male and female outpatients with an opioid use disorder who express interest in extended-release injectable naltrexone (XR-NTX) are randomized 1:1 to lofexidine/pregabalin or lofexidine/pregabalin placebo for withdrawal management and offered XR-NTX if after completing withdrawal.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
A placebo-controlled trial in which male and female outpatients with an opioid use disorder who express interest in extended-release injectable naltrexone (XR-NTX) are randomized 1:1 to lofexidine/pregabalin or lofexidine/pregabalin placebo for withdrawal management and offered XR-NTX if after completing withdrawal. It follows a UG3 study in which 90 inpatients with an OUD who expressed interest in XR-NTX were randomized 2:1 to withdrawal management with lofexidine/pregabalin or lofexidine/placebo pregabalin. Results were that the conditions were equally safe, and that lofexidine/pregabalin was more effective in reducing subjective withdrawal and keeping patients in treatment than lofexidine/placebo pregabalin.
The objectives are to study the safety and effectiveness of lofexidine/pregabalin compared to lofexidine/placebo for managing opioid withdrawal and transitioning to XR-NTX in outpatient settings.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LFX/PGB PGB/day 1=400mg, day 2-7=600mg each day, day 8=400mg, day 9=200mg, day 10=100mg LFX/day 1=1.62mg, day 2-7=2.16mg each day, day 8=1.44mg, day 9=0.72mg, day 10=0.72mg |
Drug: LFX/PGB
lofexidine tablets 0.18mg tabs
pregabalin capsules 100mg and 25mg
Other Names:
Drug: LFX/PLA-PGB
lofexidine tablets 0.18mg tabs
pregabalin capsules 0mg
Other Names:
|
| Active Comparator: LFX/PLA-PGB PLA-PGB/day 1-7= 0mg each day, day 8, 9, and 10 =0mg each day LFX/ day 1=1.62mg, day 2-7=2.16mg each day, day 8=1.44mg, day 9=0.72mg, day 10=0.72mg |
Drug: LFX/PGB
lofexidine tablets 0.18mg tabs
pregabalin capsules 100mg and 25mg
Other Names:
Drug: LFX/PLA-PGB
lofexidine tablets 0.18mg tabs
pregabalin capsules 0mg
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Subjective Opioid Withdrawal Scale (SOWS) scores [10 days per subject, through study completion (N=150)]
Subjective patient reported Opioid Withdrawal measured by the SOWS, (0-30); 0 = no withdrawal/30 = severe withdrawal
Secondary Outcome Measures
- Study detox completion [10 days per subject, through study completion (N=150)]
Proportion that receives one or more doses of study medication and completed withdrawal (Completing withdrawal management will be defined as having received at least 1 dose of study medication on day 8 and completing the SOWS-Gossop assessment on day 8); and proportion that transition to XR-NTX; adverse events
- XR-NTX IM injection [upto 2 days per subject (N=150)]
proportion that receives 380mg dose of extended-release naltrexone
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male and/or female subjects ≥ 18 years of age
-
Meet DSM-5 criteria for an Opioid Use Disorder with physiologic features. Have met 2 or more of the 11 criteria for an OUD including tolerance and withdrawal within the last 12 months
-
Interested in opioid antagonist treatment
-
Used opioids in 20 or more of the last 30 days
-
A stable address in the local area; not planning to move in the next 60 days.
-
Have documents for ID check
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Absence of medical or psychiatric conditions that are likely to interfere with study participation
-
Has 12 lead ECG demonstrating a QTc ≤450 msec and a QRS ≤120 msec. Site PI has final determination for study inclusion if readings exceed these limits. The PENN cardiologists and medical monitor are available for consultation when needed
-
Negative pregnancy test and using adequate contraception if of childbearing potential.
Exclusion Criteria:
-
Current psychotic disorder (bipolar I, schizophrenia, major depression that is not in remission
-
Alcohol, benzodiazepine, or other sedative use disorder with physiological features that require medication for detoxification
-
Allergy or other serious adverse event due to treatment with pregabalin, XR-NTX, or lofexidine
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Pending incarceration or plans to leave the immediate area in the next 30 days
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Homicidal or otherwise behaviorally disturbed requiring immediate attention
-
High risk for suicide as determined by answering 'yes' to questions 4 and/or 5 on C-SSRS
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Blood pressure <90 mm Hg (systolic) or <60 mm Hg (diastolic). If value out of normal range, the investigator and study Clinician will decide subject inclusion/exclusion on case-by-case basis
-
Heart rate and/or pulse<50 bpm at screening-sitting
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An Estimated Glomerular Filtration Rate eGFR<70 mL/min/1.73m2
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A History of, or current Seizure disorder (excluding childhood febrile seizures)
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Inability to read and/or understand English. For example, unable to understand the informed consent as demonstrated by failing to answer 9/10 questions correctly on the quiz
-
- Pregnant or breastfeeding
-
- Currently taking sympathomimetic drugs, or a thiazolidinedione antidiabetic
-
ALT and/or AST >4X upper limit of normal
-
A Child-Pugh score >7
-
Currently receiving opioids for pain management
-
In a treatment study where medication was administered in the last 30 days
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Currently using medications that are known to be strong or moderate inhibitors of CYP2D6 such as fluoxetine, paroxetine, mirabegron, bupropion, quinidine, terbinafine, cimetidine, cinacalcet, duloxetine, or fluvoxamine
-
In a methadone maintenance or buprenorphine treatment program within the last 30 days
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Pennsylvania, Treatment Research Center | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- University of Pennsylvania
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 854046