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: Terminated
• 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 (Actual): 4
• 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

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	Measure Description	Time Frame
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
Number of Treatment Emergent AEs and SAEs		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	The C-SSRS measures both suicidal ideation and suicidal behavior. The Screener contains "yes" or "no" questions in which respondents are asked to indicate whether they have experienced several thoughts or feelings relating to suicide. A significant risk of suicide is defined as a "yes" in answer to: a) questions 4 or 5 on the suicidal ideation section, or b) any questions on any item in the suicidal behavior section. This must be reported as an SAE and followed up accordingly. Additionally, if a subject responds "yes" to any of the suicidal ideation questions 1 to 3, the Investigator should apply clinical judgment to determine the need for reporting as an AE or SAE and the need for any referral.	Day 1 through Day 28
Change in Blood Pressure	Orthostatic vital signs were measured in-clinic only. When the subject is at home, only resting vital signs will be collected. Orthostatic vital signs will be measured first after the subject has been sitting for at least 5 minutes and then after the subject has been standing for at least 3 minutes. Resting vital signs only will be measured at home and will be measured after the subject has been sitting quietly for at least 5 minutes.	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	Measure Description	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)	The COWS is a clinician-administered instrument that rates 11 common opioid withdrawal signs and symptoms. These include: resting pulse rate; sweating; restlessness; pupil size; bone or joint aches; runny nose or tearing; gastrointestinal upset; tremor; yawning; anxiety or irritability; and gooseflesh skin. Lower total scores indicate a more positive clinical outcome. Score: 5-12 = mild; 13-24 = moderately severe; more than 36 = severe withdrawal. Scores range from a minimum of 0 to a maximum of 48.	Day 1 (pre-1st dose) to Days 3, 8, 15, 22 and 28
Change in the Short Opiate Withdrawal Scale of Gossop (SOWS-G)	The SOWS-Gossop scale assesses subjective symptoms of opioid withdrawal. It is a subject-rated scale consisting of 10 items that are scored on a 4-point scale of 0 = none, 1 = mild, 2 = moderate, and 3 = severe (minimum score of 0, maximum score of 30). The overall score is the simple sum of the 10 item scores. Lower observed values in SOWS-Gossop scores indicate a more positive clinical outcome.	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)	The SOWS-H scale assesses subjective symptoms of opioid withdrawal. It is a subject-rated scale consisting of 19 items that are scored on a 5-point scale of 0 = not at all, 1 = a little, 2 = moderately, 3 = quite a bit, and 4 = extremely. The overall score is the simple sum of the 19 item scores. Lower observed values in SOWS-H scores indicate a more positive clinical outcome.	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) Average Score	MCGI-R includes 2 items: A 7-point scale that allows clinicians to rate the severity of a subject's opiate withdrawal symptoms. A 4-point scale that allows clinicians to rate the degree of a subject's side effects from study drug. SEVERITY OF ILLNESS: = No at all ill; = Borderline ill; = Mildly ill; = Moderately ill; = Markedly ill; = Severely ill; = Among the most extremely ill subjects SIDE EFFECTS INDEX: = None, study drug is producing no side effects; = Do not significantly interfere with subject's functioning; = Significantly interferes with subject's functioning; = Outweighs therapeutic effect	Each scheduled evaluation (Study Visits 2, 3, 4, 5, EOS)
Modified Clinical Global Impression - Subject Version (MCGI-S)	Includes: A 7-point scale for subjects to rate the severity of opiate withdrawal symptoms. A 4-point scale for subjects to rate the degree of side effects from their study drug. SEVERITY OF OPIATE WITHDRAWAL: = No opiate withdrawal symptoms; = On the border between no to mild opiate withdrawal symptoms; = Mild opiate withdrawal symptoms; = Moderate opiate withdrawal symptoms; = Marked opiate withdrawal symptoms; = Severe opiate withdrawal symptoms; = The most severe opiate withdrawal symptoms that I have ever had SIDE EFFECTS INDEX (Scale B): = None. The study drug has no side effects; = The study drug has slight side effects, but it does NOT significantly interfere with my day to day activities; = The study drug has moderate side effects, and it DOES significantly interfere with my day to day activities; = The study drug has severe side effects, and these side effects are greater than the relief from opiate withdrawal symptoms that it provides	Each scheduled evaluation (Day 1 through Day 28)
Time to Study Drug Discontinuation	Study day of participant 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	The EQ-5D-5L is an instrument that evaluates preference for health status through 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each of which are rated on 5 levels of severity. Each dimension ranges from a minimum of "0 - I have no problems or I am not" to a maximum of "5 - I am unable to or I am extremely". The dimensions are averaged together for a single score and the change in average score from baseline is recorded.	Change from Baseline to EOS
Change in Short Form Health Survey (SF-36) Scale	The SF-36 consists of 36 questions that measure various aspects of physical and mental well-being. Precoded values are recorded for each question ranging from 0-100, with a high score defined as a more favorable health status. The items are then averaged together to create the 8 scale scores which are averaged together to create a scale. The final value reported is the average change in the averaged scale scores from baseline to end of study.	Change from baseline to End of Study, up to 55 days
Change in Insomnia Severity Index (ISI)	The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The dimensions evaluated are: severity of sleep onset, sleep maintenance and early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by the sleep difficulties. A 5-point Likert scale is used to rate each item on a scale 0 to 4 for each of the 7 items, yielding a total score ranging from 0 to 28. The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).	Change from baseline to Days 15 and End of Study, up to 55 days
Change in Hospital Anxiety and Depression Scale (HADS)	The HADS is a self-reported screening tool for anxiety and depression in nonpsychiatric clinical populations. Responses are based on the relative frequency of symptoms over the preceding week. The scale consists of 14 items, with a subscale of 7 questions for anxiety and 7 questions for depression. Patients rate each item in the subscales on a 4-point scale ranging from 0 (absence) to 3 (extreme presence). Possible scores range from 0 to 21 for each subscale. An analysis of scores on the 2 subscales supported the differentiation of each mood state into 4 ranges: non-cases (scores 0 to 7), mild cases (scores 8 to 10), moderate cases (scores 11 to 15), and severe cases (scores 16 or higher), with lower values being favorable. The subscales are then combined for a total score ranging from 0 to 42. Higher scores indicate greater levels of anxiety or depression. The value reported is the average change from baseline to End of Study.	Change from End of Study to Baseline, up to 55 days
Change in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS)	A subject selects a whole number (0 to 10) that best indicates the intensity of his/her pain. The format consists of a horizontal line which is anchored by terms defining pain levels where 0 represents no pain and 10 represents worst pain imaginable.	Baseline through Follow-up (assessed daily)
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS)	The NRS of pain intensity is a unidimensional, segmented numeric version of the visual analog scale. A subject selects a whole number (0 to 10) that best indicates the intensity of his/her pain. The format consists of a horizontal line which is anchored by terms defining pain levels where 0 represents no pain and 10 represents worst pain imaginable.	Day 1 through Day 28 (assessed daily)
Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS)	The NRS of pain intensity is a unidimensional, segmented numeric version of the visual analog scale. A subject selects a whole number (0 to 10) that best indicates the intensity of his/her pain. The format consists of a horizontal line which is anchored by terms defining pain levels where 0 represents no pain and 10 represents worst pain imaginable.	Baseline through Day 51 (assessed daily)
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS)	The NRS of pain intensity is a unidimensional, segmented numeric version of the visual analog scale. A subject selects a whole number (0 to 10) that best indicates the intensity of his/her pain. The format consists of a horizontal line which is anchored by terms defining pain levels where 0 represents no pain and 10 represents worst pain imaginable.	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 (Actual): November 27, 2019
• Study Completion (Actual): November 27, 2019

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): October 21, 2024
• Last Update Submitted That Met QC Criteria: October 18, 2024
• Last Verified: October 1, 2024

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