Opiate Withdrawal SyndromePhase 2UH3NCT05995535
Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal
A Phase 2 study testing LFX/PGB and LFX/PLA-PGB in people with Opiate Withdrawal Syndrome and Opioid Use, run by University of Pennsylvania at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Opiate Withdrawal Syndrome, Opioid Use
- What is being tested?
- LFX/PGB and LFX/PLA-PGB
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2024to 31 Aug 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
- Pending incarceration or plans to leave the immediate area in the next 30 days
- 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
- An Estimated Glomerular Filtration Rate eGFR<70 mL/min/1.73m2
- A History of, or current Seizure disorder (excluding childhood febrile seizures)
- 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
- 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
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Not yet recruiting
Mountain Manor Treatment Center
Baltimore, Maryland, 21229-3618
Marc Fishman, MD, 4102331400, Mfishman@marylandtreatment.org
kevin Wenzel, 4102331400, kwenzel@marylandtreatment.org
- Recruiting
University of Pennsylvania, Treatment Research Center
Philadelphia, Pennsylvania, 19104
Kyle Kampman, MD, (215)222-3200, kampman@mail.med.upenn.edu
Sabrina A Poole, PsyD, 2157468802, spoole@pennmedicine.upenn.edu
About this study
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.
Read the 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.
- Conditions
- Opiate Withdrawal Syndrome, Opioid Use
- Being tested
- LFX/PGB, LFX/PLA-PGB
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LFX/PGBDrug
Also called Lucemyra, lyrica
lofexidine tablets 0.18mg tabs
pregabalin capsules 100mg and 25mg
LFX/PLA-PGBDrug
Also called Lucemyra, placebo pregabalin
lofexidine tablets 0.18mg tabs
pregabalin capsules 0mg
| Study group | Role | What they receive |
|---|---|---|
| LFX/PGB | Experimental | 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 Receives: Drug: LFX/PGB; Drug: LFX/PLA-PGB |
| LFX/PLA-PGB | Active comparator | 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 Receives: Drug: LFX/PGB; Drug: LFX/PLA-PGB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjective Opioid Withdrawal Scale (SOWS) scores
Subjective patient reported Opioid Withdrawal measured by the SOWS, (0-30); 0 = no withdrawal/30 = severe withdrawal
Measured: 10 days per subject, through study completion (N=150)
Secondary outcomes (2)
Study detox completion
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
Measured: 10 days per subject, through study completion (N=150)
XR-NTX IM injection
proportion that receives 380mg dose of extended-release naltrexone
Measured: upto 2 days per subject (N=150)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2023
- Study start1 Jan 2024
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opiate Withdrawal SyndromeStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Active pregabalin plus lofexidine versus placebo pregabalin plus lofexidine
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kyle Kampman, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05995535
- Sponsor's protocol ID
- 854046
- Acronym
- UH3
- Status last verified
- Jan 2026
- First submitted
- 1 Aug 2023
- Last updated
- 13 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal
- ClinicalTrials.gov ID
- NCT05995535
- Acronym / sponsor ID
- UH3 / 854046
- Conditions
- Opiate Withdrawal Syndrome, Opioid Use
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 16 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Active pregabalin plus lofexidine versus placebo pregabalin plus lofexidine
| Arm | Type | Receives |
|---|---|---|
| LFX/PGB | Experimental | Drug: LFX/PGB, Drug: LFX/PLA-PGBPGB/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 |
| LFX/PLA-PGB | Active comparator | Drug: LFX/PGB, Drug: LFX/PLA-PGBPLA-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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (19 listed)
- 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
- Pending incarceration or plans to leave the immediate area in the next 30 days
- Homicidal or otherwise behaviorally disturbed requiring immediate attention
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LFX/PGBAlso: Lucemyra, lyricalofexidine tablets 0.18mg tabs pregabalin capsules 100mg and 25mg | Drug | LFX/PGB, LFX/PLA-PGB |
| LFX/PLA-PGBAlso: Lucemyra, placebo pregabalinlofexidine tablets 0.18mg tabs pregabalin capsules 0mg | Drug | LFX/PGB, LFX/PLA-PGB |
Primary outcome
Subjective Opioid Withdrawal Scale (SOWS) scores
Time frame: 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
2 secondary outcomes
Study detox completion
Time frame: 10 days per subject, through study completion (N=150)
XR-NTX IM injection
Time frame: upto 2 days per subject (N=150)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LFX/PGB and LFX/PLA-PGB in people with Opiate Withdrawal Syndrome and Opioid Use, run by University of Pennsylvania at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kyle M Kampman, MD (215-746-2764, Kampman@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subjective Opioid Withdrawal Scale (SOWS) scores (time frame: 10 days per subject, through study completion (N=150)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.