Randomized, Double-Blind, Placebo-Controlled Pilot Study on the Safety and Effectiveness of LUCEMYRA During an Opioid Taper in Treatment of Withdrawal
- Registration Number
- NCT04070157
- Lead Sponsor
- USWM, LLC (dba US WorldMeds)
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - Lofexidine Lofexidine -
- Primary Outcome Measures
Name Time Method 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 Day 1 through Day 28 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.
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 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.
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
Name Time Method 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 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.
Change in Average Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 1 through Day 28 (assessed daily) 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.
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 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.
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 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.
Modified Clinical Global Impression - Rater Version (MCGI-R) Average Score Each scheduled evaluation (Study Visits 2, 3, 4, 5, EOS) 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:
1. = No at all ill
2. = Borderline ill
3. = Mildly ill
4. = Moderately ill
5. = Markedly ill
6. = Severely ill
7. = Among the most extremely ill subjects
SIDE EFFECTS INDEX:
1. = None, study drug is producing no side effects
2. = Do not significantly interfere with subject's functioning
3. = Significantly interferes with subject's functioning
4. = Outweighs therapeutic effectModified Clinical Global Impression - Subject Version (MCGI-S) Each scheduled evaluation (Day 1 through Day 28) 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:
1. = No opiate withdrawal symptoms
2. = On the border between no to mild opiate withdrawal symptoms
3. = Mild opiate withdrawal symptoms
4. = Moderate opiate withdrawal symptoms
5. = Marked opiate withdrawal symptoms
6. = Severe opiate withdrawal symptoms
7. = The most severe opiate withdrawal symptoms that I have ever had
SIDE EFFECTS INDEX (Scale B):
1. = None. The study drug has no side effects
2. = The study drug has slight side effects, but it does NOT significantly interfere with my day to day activities
3. = The study drug has moderate side effects, and it DOES significantly interfere with my day to day activities
4. = The study drug has severe side effects, and these side effects are greater than the relief from opiate withdrawal symptoms that it providesTime to Study Drug Discontinuation Day 1 through Day 28 Study day of participant discontinuation.
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 Change from Baseline to EOS 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 in Short Form Health Survey (SF-36) Scale Change from baseline to End of Study, up to 55 days 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 in Insomnia Severity Index (ISI) Change from baseline to Days 15 and End of Study, up to 55 days 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 in Hospital Anxiety and Depression Scale (HADS) Change from End of Study to Baseline, up to 55 days 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 in Average Chronic Pain as Measured by the Numeric Rating Scale (NRS) Baseline through Follow-up (assessed daily) 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.Change in Worst Chronic Pain as Measured by the Numeric Rating Scale (NRS) Baseline through Day 51 (assessed daily) 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.
Change in Worst Overall Pain as Measured by the Numeric Rating Scale (NRS) Day 1 through Day 28 (assessed daily) 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.
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
Trial Locations
- Locations (12)
Vitamed Research
🇺🇸Rancho Mirage, California, United States
Gold Coast Research, LLC
🇺🇸Plantation, Florida, United States
Duke Innovation Pain Therapies Clinic at Brier Creek
🇺🇸Raleigh, North Carolina, United States
University of Rochester
🇺🇸Rochester, New York, United States
Neuroscience Research Center, LLC
🇺🇸Overland Park, Kansas, United States
Westview Clinical Research, LLC
🇺🇸Placentia, California, United States
Georgia Clinical Research, LLC
🇺🇸Lawrenceville, Georgia, United States
Injury Care Research
🇺🇸Boise, Idaho, United States
Global Scientific Innovations
🇺🇸Evansville, Indiana, United States
Integrated Clinical Trial Services, Inc.
🇺🇸West Des Moines, Iowa, United States
Otrimed Corporation (Otrimed Clinical Research Center)
🇺🇸Edgewood, Kentucky, United States
The Center for Clinical Research, LLC
🇺🇸Winston-Salem, North Carolina, United States