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

Sponsor

USWM, LLC (dba US WorldMeds) (Industry)

Overall Status

Suspended

CT.gov ID

NCT04070157

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Aug 2, 2019

Anticipated Primary Completion Date :

Oct 31, 2022

Anticipated Study Completion Date :

Oct 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.

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

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Westview Clinical Research, LLC	Placentia	California	United States	92870
2	Vitamed Research	Rancho Mirage	California	United States	92270
3	Gold Coast Research, LLC	Plantation	Florida	United States	33317
4	Georgia Clinical Research, LLC	Lawrenceville	Georgia	United States	30044
5	Injury Care Research	Boise	Idaho	United States	83713
6	Global Scientific Innovations	Evansville	Indiana	United States	47714
7	Integrated Clinical Trial Services, Inc.	West Des Moines	Iowa	United States	50265
8	Neuroscience Research Center, LLC	Overland Park	Kansas	United States	66210
9	Otrimed Corporation (Otrimed Clinical Research Center)	Edgewood	Kentucky	United States	41017
10	University of Rochester	Rochester	New York	United States	14624
11	Duke Innovation Pain Therapies Clinic at Brier Creek	Raleigh	North Carolina	United States	27617
12	The Center for Clinical Research, LLC	Winston-Salem	North Carolina	United States	27103