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

• ClinicalTrials.gov Identifier: NCT04070157
• Recruitment Status: Suspended
• First Posted: August 28, 2019
• Last Update Posted: March 14, 2022
• Sponsor: USWM, LLC (dba US WorldMeds)
• Information provided by (Responsible Party): USWM, LLC (dba US WorldMeds)

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Opioid Withdrawal (Disorder)	Drug: Lofexidine; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: All subjects, study personnel (including the Investigator, study coordinator(s), pharmacist/designee), and the Sponsor will be blinded to the identity of the study drug (active or placebo) administered to subjects.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: August 2, 2019
• Estimated Primary Completion Date: October 31, 2022
• Estimated Study Completion Date: October 31, 2022

Arms and Interventions

Arm	Intervention/treatment
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
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.

Outcome Measures

Primary Outcome Measures :

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

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Westview Clinical Research, LLC

Placentia, California, United States, 92870

Vitamed Research

Rancho Mirage, California, United States, 92270

United States, Florida

Gold Coast Research, LLC

Plantation, Florida, United States, 33317

United States, Georgia

Georgia Clinical Research, LLC

Lawrenceville, Georgia, United States, 30044

United States, Idaho

Injury Care Research

Boise, Idaho, United States, 83713

United States, Indiana

Global Scientific Innovations

Evansville, Indiana, United States, 47714

United States, Iowa

Integrated Clinical Trial Services, Inc.

West Des Moines, Iowa, United States, 50265

United States, Kansas

Neuroscience Research Center, LLC

Overland Park, Kansas, United States, 66210

United States, Kentucky

Otrimed Corporation (Otrimed Clinical Research Center)

Edgewood, Kentucky, United States, 41017

United States, New York

University of Rochester

Rochester, New York, United States, 14624

United States, North Carolina

Duke Innovation Pain Therapies Clinic at Brier Creek

Raleigh, North Carolina, United States, 27617

The Center for Clinical Research, LLC

Winston-Salem, North Carolina, United States, 27103

Sponsors and Collaborators

USWM, LLC (dba US WorldMeds)

Investigators

• Study Director: John Peppin, DO; US WorldMeds Contract Medical Monitor

More Information

• Responsible Party: USWM, LLC (dba US WorldMeds)
• ClinicalTrials.gov Identifier: NCT04070157
• Other Study ID Numbers: USWM-LX1-2010
• First Posted: August 28, 2019
• Last Update Posted: March 14, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by USWM, LLC (dba US WorldMeds):

Opioid Withdrawal Syndrome; OWS; Opioid taper; Opioid withdrawal; Opioid reduction; Stopping opioids; Opioid discontinuation; non-opioid pain management

Additional relevant MeSH terms:

Substance Withdrawal Syndrome; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Lofexidine; Clonidine; Antihypertensive Agents; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Analgesics; Sympatholytics; Autonomic Agents