Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) for Relief of Moderate to Severe Pain in Patients With Osteoarthritis or Low Back Pain Who Require Opioid Treatment for an Extended Period of Time

• Percentage of patients who withdraw from the study [ Time Frame: during the 12-week double-blind treatment period ] [ Designated as safety issue: No ]
• Time from baseline to patient withdrawal from the study [ Time Frame: during the 12-week double-blind treatment period ] [ Designated as safety issue: No ]
• Weekly average of daily API scores [ Time Frame: at weeks 1, 2, 4, 8, and 12 ] [ Designated as safety issue: No ]
  Based on the 11-point Numerical Rating Scale (NRS-11) from electronic diary
• Weekly average of daily Worst Pain Intensity (WPI) [ Time Frame: at weeks 1, 2, 4, 8, and 12 ] [ Designated as safety issue: No ]
  Based on NRS-11 from electronic diary
• Weekly API increase from baseline exceeding 33% and 50% [ Time Frame: during the 12-week double-blind treatment period ] [ Designated as safety issue: No ]
• Rescue medication usage [ Time Frame: during the first 2 weeks of the 12-week double-blind treatment period ] [ Designated as safety issue: No ]
  - first time frame regarding Rescue medication usage
• Rescue medication usage [ Time Frame: after the first 2 weeks of the 12-week double-blind treatment period ] [ Designated as safety issue: No ]
  - second time frame regarding Rescue medication usage
• Clinician Assessment of Patient Function (CAPF) ratings [ Time Frame: at weeks 4, 8, and 12 or last postbaseline observation ] [ Designated as safety issue: No ]
• Patient Assessment of Function (PAF) ratings [ Time Frame: at weeks 4, 8, and 12 or last postbaseline observation ] [ Designated as safety issue: No ]
• Clinician Global Impression of Severity of Illness (CGI-S) ratings in regard to pain [ Time Frame: at weeks 1, 2, 4, 8, and 12 or last postbaseline observation ] [ Designated as safety issue: No ]
• Brief Pain Inventory-Short Form (BPI-SF) scores [ Time Frame: at weeks 1, 2, 4, 8, and 12 or last postbaseline observation ] [ Designated as safety issue: No ]
• 36-Item Short Form Health Survey (SF-36) scores [ Time Frame: at week 12 or last postbaseline observation ] [ Designated as safety issue: No ]
• Evaluate the safety and tolerability of hydrocodone extended-release tablets [ Time Frame: during the 12-week double-blind treatment period ] [ Designated as safety issue: Yes ]
  • adverse events, vital signs, and concomitant medication
  • physical exam findings and clinical lab test results at week 12
  • pure tone audiometry at titration, at baseline, and at week 12
  • Subjective Opiate Withdrawal Scale (SOWS) scores, daily during the first 4 weeks, then at weeks 8 and 12
  • Clinical Opiate Withdrawal Scale (COWS) scores at weeks 1, 2, 4, 8, and 12
  • Addiction Behavior Checklist (ABC) scores at titration and at weeks 1, 4, 8, and 12
  • Current Opioid Misuse Measure (COMM) scores at titration and at weeks 1, 4, 8, and 12
  • electrocardiograms (ECGs) at week 12

The primary objective of this study is to evaluate efficacy of hydrocodone extended-release tablets compared with placebo in alleviating moderate to severe pain in patients with osteoarthritis or low back pain as assessed by the weekly Average Pain Intensity (API) at week 12.

• Drug: Hydrocodone
  Hydrocodone at 15 to 90 mg, administered every 12 hours
• Drug: Placebo
  Matching Placebo

• Experimental: Hydrocodone
  Intervention: Drug: Hydrocodone
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• The patient is able to speak English and is willing to provide written informed consent, including a written opioid agreement, to participate in this study.
• The patient must be willing and able to successfully self-administer the study drug, comply with study restrictions, complete the electronic diary, and return to the clinic for scheduled study visits as specified in this protocol.
• Women of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study, and have a negative pregnancy test at screening.
• The patient has pain of at least 3 months' duration associated with osteoarthritis or low back pain.
• The patient reports an average pain intensity score, over the prior 24 hours, of 5 or more on the NRS-11.
• If the patient is receiving physical therapy, biofeedback therapy, acupuncture therapy, or herbal remedies, these therapies must remain unchanged during the study.
• The patient must not participate in other study involving an investigational agent while enrolled into the present study.

Exclusion Criteria:

• The patient has known or suspected hypersensitivities, allergies, or other contraindications to any ingredient in the study drug.
• The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse with the exception of nicotine or caffeine.
• The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data.
• The patient is taking a total (ie, around-the-clock plus rescue medication) of more than 135 mg/day of oxycodone, or equivalent, during the 14 days prior to screening.
• The patient has a history of suicidality.
• The patient is expected to have surgery during the study.
• The patient's primary painful condition under study is related to any source of chronic pain other than osteoarthritis or low back pain.
• The patient is pregnant or lactating.
• The patient has active malignancy.
• The patient has human immunodeficiency virus (HIV).
• In the judgment of the investigator, the patient has any clinically significant deviation from normal in the physical examination and/or clinical laboratory test values.
• The patient has cardiopulmonary disease that would, in the opinion of the investigator, significantly increase the risk of treatment with opioids.
• The patient has participated in a study involving an investigational drug in the previous 30 days.
• The patient has received a monoamine oxidase inhibitor (MAOI) within 14 days before the first treatment with study drug.
• The patient has any other medical condition or is receiving concomitant medication/therapy (e.g., regional nerve block) that would, in the opinion of the investigator, compromise the patient's safety or compliance with the study protocol, or compromise collected data.
• The patient is involved in active litigation in regard to the pain currently being treated.
• The patient has a positive urine drug screen (UDS) that is not medically explainable.
• The investigator feels that the patient is not suitable for the study for any reason.