Randomized, Double-Blind, Placebo-Controlled Pilot Study on the Safety and Effectiveness of LUCEMYRA During an Opioid Taper in Treatment of Withdrawal (TAPER)

A Randomized, Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Safety and Effectiveness of LUCEMYRA in the Treatment of Opioid Withdrawal During an Opioid Taper in Subjects With Chronic Non-Cancer Pain

Stopping prescription opioid pain medications can be difficult due to withdrawal symptoms. This study will test if LUCEMYRA helps reduce withdrawal symptoms and helps more people reduce their opioid dose compared to placebo.

Study Overview

• Status: Suspended
• Conditions: Opioid Withdrawal (Disorder)
• Intervention / Treatment: Drug: Lofexidine; Drug: Placebo

Detailed Description

This randomized, double-blind, placebo-controlled pilot study will evaluate the safety and effectiveness of LUCEMYRA in the treatment of opioid withdrawal during an opioid taper in subjects with chronic non-cancer pain.

Subjects will begin a planned 14-day complete taper of their pre-study opioid medications and will be randomly assigned (1:1) to either LUCEMYRA or matching placebo. Study drug will be administered through the opioid taper and for 5 days after the opioid taper is completed. Study drug will then be tapered over a 4-day period for a total of approximately 21 days exposure to study drug.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Placentia, California, United States, 92870
      • Westview Clinical Research, LLC
    • Rancho Mirage, California, United States, 92270
      • Vitamed Research
  • Florida
    • Plantation, Florida, United States, 33317
      • Gold Coast Research, LLC
  • Georgia
    • Lawrenceville, Georgia, United States, 30044
      • Georgia Clinical Research, LLC
  • Idaho
    • Boise, Idaho, United States, 83713
      • Injury Care Research
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Global Scientific Innovations
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Integrated Clinical Trial Services, Inc.
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • NeuroScience Research Center, LLC
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Otrimed Corporation (Otrimed Clinical Research Center)
  • New York
    • Rochester, New York, United States, 14624
      • University of Rochester
  • North Carolina
    • Raleigh, North Carolina, United States, 27617
      • Duke Innovation Pain Therapies Clinic at Brier Creek
    • Winston-Salem, North Carolina, United States, 27103
      • The Center for Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject can provide written informed consent.
• Chronic non-cancer pain diagnosis such as low back pain, chronic neck pain, osteoarthritis, and prolonged post-surgical pain with daily pain for a minimum of 6 months.
• Self-reported use of prescribed oral opioid medication(s) (tablets, pills or capsules) of at least 50 morphine mg equivalent (MME) but no higher than 240 mg MME daily or near daily (≥5 days per week) for at least 12 weeks and seeking to discontinue their opioid medication.
• Willing to be treated with non-opioid treatments for pain (in addition to opioid being tapered) for duration of study.
• Willing to abstain from alcohol use during the study.
• Willing to partner with his or her pain physician on a subject-centered pain management plan during the study.
• In generally good health, in the opinion of the Investigator, other than the underlying chronic pain syndrome
• Women of childbearing potential must have a negative pregnancy test at Screening.
• Non-pregnant, non-lactating women who are postmenopausal, naturally or surgically sterile, or who agree to use acceptable contraceptive methods throughout the course of the study.
• Other criteria will be discussed in detail with potential subjects by Site Investigator

Exclusion Criteria:

• Has a primary diagnosis of complex regional pain syndrome, central neuropathic pain, somatoform pain syndromes, acute nerve root compression, any acute or progressive infectious, inflammatory, or neurological process.
• Taking methadone, buprenorphine, fentanyl rapid acting products, tapentadol, tramadol, butorphanol, meperidine, or levorphanol for any reason
• Liver disease that requires medication or medical treatment, and/or AST or ALT levels greater than 3 x ULN.
• Gastrointestinal or renal disease, which would significantly impair absorption, metabolism or excretion of study drug, or would require medication or medical treatment.
• Has a diagnosis of epilepsy or history of seizures.
• Cardiovascular abnormalities at Screening and before randomization (stable hypertension permitted)
• Self-reported or evidence of opioid use disorder (OUD) or other substance use disorder within last 12 months
• Any severe or unstable psychiatric disorder including post-traumatic stress disorder, schizophrenia, bipolar disorder, major depression, substance abuse, or suicidality as determined by the Investigator.
• Subject answers "yes" to "suicidal ideation" in prior 24 months to any items 1 through 5 on the C-SSRS, or subject answers "yes" to any lifetime "suicidal behavior" item on the C-SSRS.
• Any anticipated or scheduled surgery during the study period or within 30 days before Screening.
• Other criteria will be discussed in detail with potential subjects by site Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.
Experimental: Lofexidine	Drug: Lofexidine; Lofexidine 0.18 mg tablets. Dosing will begin with 1 tablet administered every 5-6 hours, up to 4 times day. The dose may be titrated but not to exceed 4 tablets 4 times a day.; Other Names: lofexidine hydrochloride; LUCEMYRA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of treatment emergent AEs and SAEs by system organ class and preferred term	Day 1 through Day 28
Number and percent of subjects reporting TEAEs resulting in study drug discontinuation	Day 1 through Day 28
Percentage of subjects with treatment-emergent elevated liver function tests	Day 1 through Day 28
Percentage of subjects identified as suicide risk with Columbia Suicide Severity Rating Scale	Day 1 through Day 28
Change in Blood Pressure	Baseline to Days 1, 2, 3, 7, 8, 14, 15, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 and 28
Change in Pulse	Baseline to Days 1, 2, 3, 7, 8, 14, 15, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 and 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of subjects who successfully complete each scheduled dose reduction and the opioid taper to complete opioid discontinuation	Day 1 through Day 28
Change in Clinical Opiate Withdrawal Scale (COWS)	Day 1 (pre-1st dose) to Days 3, 8, 15, 22 and 28
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G)	Day 1 (pre-1st dose) to Days 1 (at bedtime), 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 and 28
Change in Subjective Opiate WIthdrawal Scale of Handelsman (SOWS-H)	Day 1 (pre-1st dose) to Days 1 (at bedtime), 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 and 28
Modified Clinical Global Impression - Rater Version (MCGI-R)	Each scheduled evaluation (Day 1 through Day 28)
Modified Clinical Global Impression - Subject Version (MCGI-S)	Each scheduled evaluation (Day 1 through Day 28)
Time to study drug discontinuation	Day 1 through Day 28
Number of non-opioid concomitant medications for withdrawal symptoms used by study day	Day 1 through Day 28
Change in EuroQol 5-Dimension 5-Level (EQ-5D-5L) scale	Baseline to Days 28 and 51
Change in Short Form Health Survey (SF-36) scale	Baseline to Day 28
Change in Insomnia Severity Index (ISI)	Baseline to Days 15 and 28
Change in Hospital Anxiety and Depression Scale (HADS)	Baseline to Day 28
Change in Average Chronic Pain as measured by the Numeric Rating Scale (NRS)	Baseline through Day 51 (assessed daily)
Change in Average Overall Pain as measured by the Numeric Rating Scale (NRS)	Day 1 through Day 28 (assessed daily)
Change in Worst Chronic Pain as measured by the Numeric Rating Scale (NRS)	Baseline through Day 51 (assessed daily)
Change in Worst Overall Pain as measured by the Numeric Rating Scale (NRS)	Day 1 through Day 28 (assessed daily)
Change in daily opioid dose expressed as morphine equivalent dose (MED)	Baseline through Day 28
Change in daily opioid dose as a percentage of the baseline MED	Baseline through Day 28

Collaborators and Investigators

• Sponsor: USWM, LLC (dba US WorldMeds)
• Investigators: Study Director: John Peppin, DO, US WorldMeds Contract Medical Monitor

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2019
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): October 31, 2022

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: August 23, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 14, 2022
• Last Update Submitted That Met QC Criteria: March 11, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Opioid withdrawal; Opioid Withdrawal Syndrome; OWS; Opioid taper; Opioid reduction; Stopping opioids; Opioid discontinuation; non-opioid pain management
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Substance Withdrawal Syndrome; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Narcotic Antagonists; Sympatholytics; Clonidine; Lofexidine
• Other Study ID Numbers: USWM-LX1-2010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No