Clinical trial NCT05995535: Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal
Official title: Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Opiate Withdrawal Syndrome
Opioid Use
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2023-08-16
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Active pregabalin plus lofexidine versus placebo pregabalin plus lofexidine
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Male and/or female subjects ≥ 18 years of age
2. 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
3. Interested in opioid antagonist treatment
4. Used opioids in 20 or more of the last 30 days
5. A stable address in the local area; not planning to move in the next 60 days.
6. Have documents for ID check
7. Absence of medical or psychiatric conditions that are likely to interfere with study participation
8. 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
9. Negative pregnancy test and using adequate contraception if of childbearing potential.

Exclusion Criteria:

1. Current psychotic disorder (bipolar I, schizophrenia, major depression that is not in remission
2. Alcohol, benzodiazepine, or other sedative use disorder with physiological features that require medication for detoxification
3. Allergy or other serious adverse event due to treatment with pregabalin, XR-NTX, or lofexidine
4. Pending incarceration or plans to leave the immediate area in the next 30 days
5. Homicidal or otherwise behaviorally disturbed requiring immediate attention
6. High risk for suicide as determined by answering 'yes' to questions 4 and/or 5 on C-SSRS
7. 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
8. Heart rate and/or pulse\<50 bpm at screening-sitting
9. An Estimated Glomerular Filtration Rate eGFR\<70 mL/min/1.73m2
10. A History of, or current Seizure disorder (excluding childhood febrile seizures)
11. 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
12. 12. Pregnant or breastfeeding
13. 13. Currently taking sympathomimetic drugs, or a thiazolidinedione antidiabetic
14. ALT and/or AST \>4X upper limit of normal
15. A Child-Pugh score \>7
16. Currently receiving opioids for pain management
17. In a treatment study where medication was administered in the last 30 days
18. 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
19. In a methadone maintenance or buprenorphine treatment program within the last 30 days

Primary outcomes:
measure: Subjective Opioid Withdrawal Scale (SOWS) scores
timeFrame: 10 days per subject, through study completion (N=150)
Secondary outcomes:
measure: Study detox completion
timeFrame: 10 days per subject, through study completion (N=150)
measure: XR-NTX IM injection
timeFrame: upto 2 days per subject (N=150)
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Mountain Manor Treatment Center
state: Maryland
city: Philadelphia
country: United States
facility: University of Pennsylvania, Treatment Research Center
state: Pennsylvania
Study officials:
References: