Clinical trial NCT04218240: Combining Pregabalin (LYRICA®) With Lofexidine (LUCEMYRATM) to Treat OPIOID Withdrawal
Official title: Combining Pregabalin (LYRICA®) With Lofexidine (LUCEMYRATM): Can it Increase the Success of Transition to Naltrexone?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid Withdrawal
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2020-01-06
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: for the primary comparison of longitudinal subjective withdrawal measures, comparing the groups on rate of decrease across detox days, using a linear group by time effect for the mixed effects models described above. We have one primary outcome, so use an alpha level of 0.05, and we use two-sided tests. 90 subjects, 30 from each of three sites, who will be randomized into two groups, with 30 assigned to Lofexidine plus Placebo, and 60 to Lofexidine plus a starting daily dose of 400 mg of pregabalin and increasing to 600mg Pregabalin on day 2.
Primary purpose: TREATMENT

Brief summary: A phase II double-blind placebo-controlled parallel group clinical trial that will randomize 90 subjects to investigate whether pregabalin (PGB) combined with Lofexidine (LFX) can reduce opioid withdrawal-related subjective effects, and investigate, whether the PGB/LFX combination can increase the proportion of patients with an opioid use disorder (OUD) who complete detoxification and transition to antagonist treatment with extended-release injectable naltrexone (XR-NTX).

Detailed description: An inpatient detoxification study where pregabalin (PBG) will be given orally at a starting dose of up to 600 mg daily (group 1) tapered to 100 mg daily over 7 days; given with lofexidine (LFX) starting at 2.16 mg daily and declining to 0.72 mg over 7 days. On day 8, subjects are offered an injection of XR-NTX if they provide a urine sample that is negative for opioids and buprenorphine and pass a naloxone challenge. All subjects, regardless of whether or not they receive XR-NTX, will be given a referral and appointment for follow-up treatment when they leave the inpatient detoxification program.

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 2 or more of the 11 DSM 5 criteria for opioid disorder including tolerance and withdrawal features in the last 12 months
3. Interested in opioid antagonist treatment
4. Have used opioids in 20 or more of the last 30 days
5. Have a stable address in the local area; not planning to move; have documents for ID check
6. Absence of medical or psychiatric conditions that are likely to interfere with study participation
7. Have a 12 lead ECG demonstrating a QTc ≤450 msec and a QRS interval ≤120 msec. The site PI has the final determination for inclusion into the study for ECGs unless there is a question of QT prolongation or other factors (QTc/Fre uses the Frederica formula (QTc = QT/RR(1/3)). If consultation is needed, the PENN cardiologists and the medical monitor should be contacted
8. If female, have a negative pregnancy test and uses adequate contraception if of childbearing potential

Exclusion Criteria:

1. Current psychotic disorder (bipolar I, schizophrenia, major depression with psychotic features,) as defined by the MINI
2. An alcohol, benzodiazepine, or other sedative use disorder with physiological features that require medication for detoxification
3. History of allergy or other serious adverse event due to treatment with pregabalin, XR-NTX, or lofexidine
4. Pending incarceration 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 at screening
7. Blood pressure \<90 mm Hg (systolic) or \<60 mm Hg (diastolic). If this value is out of normal range, the investigator and a study clinician will decide subject inclusion or exclusion on a case-by-case basis
8. Heart rate and/or pulse\<50 bpm at screening-sitting
9. An Estimated Glomerular Filtration Rate eGFR\<90 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. Pregnant or breastfeeding
13. Currently taking sympathomimetic drugs, or a thiazolidinedione antidiabetic
14. An ALT and/or AST test that is at \>4X the top 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-Gossop (SOWS) Scale Score
timeFrame: 7 days
Secondary outcomes:
measure: Completion of Withdrawal Management
timeFrame: 7 days
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Mountain Manor Treatment Center
state: Maryland
city: New York
country: United States
facility: John Mariani
state: New York
city: Philadelphia
country: United States
facility: Treatment Research Center
state: Pennsylvania
Study officials:
affiliation: Office of Research Administration, Univ. of Pennsylvania
name: Stuart Watson
role: STUDY_DIRECTOR
References: