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

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

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

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.