Efficacy and Safety of Hydrocodone Bitartrate (HYD) in Subjects With Moderate to Severe Chronic Low Back Pain

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the analgesic efficacy and safety of HYD tablets 20 to 120 mg once-daily dose compared to placebo in subjects with moderate to severe chronic low back pain uncontrolled by their current stable analgesic regimen

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Study With an Open-label Run-in to Assess the Efficacy and Safety of Hydrocodone Bitartrate (HYD) Tablets 20 to 120 mg Once-daily in Subjects With Moderate to Severe Chronic Low Back Pain

Conditions
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Chronic Low Back Pain

Intervention / Treatment
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* Drug: Hydrocodone bitartrate q24h film-coated tablets
* Drug: Placebo to match hydrocodone bitartrate q24h tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria include: Male and female subjects ≥ 18 years of age with moderate to severe, chronic low back pain (lasting several hours daily) as their predominant pain condition for at least 3 months prior to the screening visit; Subjects whose low back pain is not adequately treated prior to the screening visit with their stable incoming analgesic regimen; Subjects deemed by the investigator/medically qualified designee (must be MD or DO) to be appropriate candidates for the protocol specified, around the clock HYD therapeutic regimen; Female subjects who are premenopausal or postmenopausal less than 1 year and who have not had surgical sterilization (ie, tubal ligation, partial or complete hysterectomy) must have a negative serum pregnancy test, be nonlactating, and willing to use adequate and reliable contraception throughout the study (eg, barrier with additional spermicidal foam or jelly, intra-uterine device, hormonal contraception). Exclusion Criteria include: Subjects taking > 100 mg/day oxycodone or equivalent during last 14 days prior to screening visit; Subjects who cannot or will not agree to completely stop all incoming opioid and nonopioid analgesic medications and other medications used for chronic pain, excluding herbal and nutraceutical medications; Subjects who cannot or will not agree to stop local regional pain treatments during the study (nerve/plexus blocks or ablation, neurosurgical procedures for pain control, botulinum toxin injections for control of chronic low back pain, steroid injections in the lower back or inhalation analgesia). The subject must not have had a nerve/plexus block within 4 weeks of the screening visit, neuroablation within 6 months of the screening visit, a botulinum toxin injection in the low back region within 3 months of the screening visit, steroid injections in the lower back within 6 weeks of the screening visit, or intravenous or intramuscular steroid injections within 4 weeks of the screening visit; Subjects who have used any investigational medication within 30 days prior to the first dose of study medication; Subjects with any history of seizures (subjects with history of pediatric febrile seizures may participate in the study) or increase in intracranial pressure; Subjects with current uncontrolled depression or other uncontrolled psychiatric disorder (subjects with controlled depression or other psychiatric disorder must be on a stable medication for ≥ 1 month prior to the screening visit to participate in the study); Subjects with a history of alcohol, medication, or illicit drug abuse or addiction and/or history of opioid abuse or addiction at any time; Subjects with clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling pacemaker; Subjects with unstable respiratory disease that, in the opinion of the investigator, precludes entry into this study; Subjects with evidence of impaired liver function upon entry into the study (laboratory test values ≥ 3 times the upper limit of the laboratory reference (normal) range (ULN) for aspartate transaminase [AST/SGOT] or alanine transaminase [ALT/SGPT], or values > 2 times the ULN for alkaline phosphatase), or total bilirubin level > 1.5 times the ULN or, in the opinion of the investigator/medically qualified designee (must be MD or DO), liver function impairment to the extent that the subject should not participate in this study; Subjects with evidence of impaired kidney function upon entry into the study (ie, serum creatinine ≥ 2.5 mg/dL); Subjects with biliary tract disease, hypothyroidism, adrenal cortical insufficiency, or any other medical condition that, in the opinion of the investigator, is inadequately treated and precludes entry into the study; Subjects who had surgical procedures directed towards the source of chronic low back pain within 6 months of the screening visit or scheduled for surgery of the lower back or any other major surgery during the study conduct period; Subjects with history of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated; Subjects with any condition in which opioids are contraindicated, eg, severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma, or paralytic ileus; Subjects who are allergic to hydrocodone or who have a history of allergies to other opioids. This does not include subjects who have experienced common opioid side effects (eg, nausea, constipation); Subjects receiving monoamine oxidase inhibitors (MAOIs) or who have been taking MAOIs within 2 weeks of the screening visit. Other protocol-specific inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydrocodone bitartrate<br>Hydrocodone bitartrate (HYD) once daily (q24h) tablets | Drug: Hydrocodone bitartrate q24h film-coated tablets<br>* Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily<br>* Other names: Hysingla ER;|
| Placebo Comparator: Placebo<br>Placebo to match hydrocodone bitartrate once daily tablets | Drug: Placebo to match hydrocodone bitartrate q24h tablets<br>* Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Pain Intensity for Average Pain Over the Last 24 Hours Score | Mean pain intensity for average pain over the last 24 hours score (on an 11-point numerical rating scale where 0 = no pain and 10 = pain as bad as you can imagine). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R) - Sleep Disturbance Subscale | The MOS Sleep-R is a brief, self-administered 12-item assessment designed to measure key aspects of sleep. It includes a sleep problems index and 6 subscales - sleep disturbance, sleep adequacy, daytime somnolence, snoring, awaken short of breath or with headache, and quantity of sleep. The sleep disturbance subscale comprised the responses to questions 1, 3, 7, and 8 on the assessment. The individual responses for each question were recorded on a 5-point scale with options ranging from 1 - all of the time to 5 - none of the time. Sleep disturbance scores were transformed linearly on a scale of 0-100. A higher value indicates a better score; therefore, a higher score indicates a better sleep pattern. | Weeks 4, 8, and 12 | 
| Patient Global Impression of Change (PGIC) | The PGIC is an ordinal scale which assesses the change in overall status relative to the start of the study. The scale has only 1 item, which measures global change of overall status by the subject on a 7-point scale (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse), where 1 = very much improved and 7 = very much worse. The proportion of subjects responding very much improved and much improved was summarized by treatment group. | Week 12 | 
| Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline | A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the mean pain intensity at week 12 of the double-blind period. | Baseline to Week 12 | 
| Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline | A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the mean pain intensity at week 12 of the double-blind period. | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Opioid