NUCYNTA® ER: WELL-DEFINED TOLERABILITY1

Oxycodone CR was included in the study as an active control to confirm the sensitivity of the pain models1

DISCONTINUATION RATES DUE TO TREATMENT-EMERGENT ADVERSE EVENTS (TEAEs) IN A CHRONIC LOW BACK PAIN STUDY1

Chart showing study on subjects with chronic low back pain who received at least one dose of study drug

Study Design +
  • Safety population (N=965): All subjects with chronic low back pain who received at least 1 dose of study drug
  • Among placebo-treated patients (21%), lack of efficacy was the most common reason for discontinuation

Oxycodone is the opioid ingredient in OxyContin®.
OxyContin® is a registered trademark of Purdue Pharma LP.2

ADVERSE REACTIONS:

The most common reasons for discontinuation due to adverse reactions in eight Phase 2/3 pooled studies reported by ≥1% in any NUCYNTA® ER dose group for NUCYNTA® ER- and placebo-treated patients were nausea (4% vs 1%), dizziness (3% vs <1%), vomiting (3% vs <1%), somnolence (2% vs <1%), constipation (1% vs <1%), headache (1% vs <1%), and fatigue (1% vs <1%), respectively.

Study design:

In a prospective, randomized, double-blind, active- and placebo-controlled, multicenter phase 3 study, subjects with moderate to severe chronic low back pain (N=981) were selected to evaluate the efficacy and safety of NUCYNTA® ER. Subjects were randomized in a 1:1:1 ratio to receive controlled, adjustable doses of NUCYNTA® ER (100-250 mg bid), oxycodone CR (20-50 mg bid), or placebo bid. This study was designed with a dose ratio of 5:1 for NUCYNTA® ER to oxycodone CR. Therefore, 100 mg to 250 mg of NUCYNTA® ER and 20 mg to 50 mg oxycodone CR were studied. The study was not designed to establish equianalgesic doses. Oxycodone CR was included for analgesic assay sensitivity and not as a head-to-head comparator. The study consisted of a screening period, a washout period, a 15-week treatment period (3-week double-blind titration period followed by a 12-week double-blind maintenance period), and a follow-up period. No breakthrough medication was allowed for low back pain during maintenance period. The primary efficacy endpoint was change from baseline in mean pain intensity at Week 12 on the Numerical Rating Scale. The co-primary efficacy endpoint was change from baseline in mean pain intensity over the entire 12-week maintenance period.1

NUCYNTA® ER: WELL-DEFINED TOLERABILITY (CONTINUED)

Oxycodone CR was included in the study as an active control to confirm the sensitivity of the pain models1

INCIDENCE OF TEAEs REPORTED BY ≥2% OF SUBJECTS IN ANY TREATMENT GROUP IN A CHRONIC LOW BACK PAIN STUDY3
Chart showing adverse events for NUCYNTA® ER, placebo, and oxycodone Study Design +
  • Safety population (N=965): All subjects with chronic low back pain who received at least 1 dose of study drug
  • Incidence of TEAEs: Based on the number of subjects experiencing at least 1 adverse event, not the number of events

Oxycodone is the opioid ingredient in OxyContin®.
OxyContin® is a registered trademark of Purdue Pharma LP.2
TEAEs=treatment-emergent adverse events.

WARNINGS AND PRECAUTIONS: Use in Patients With Chronic Pulmonary Disease:

Patients with significant chronic obstructive pulmonary disease or cor pulmonale and patients having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or pre-existing respiratory depression, should be monitored for respiratory depression particularly when initiating therapy and titrating with NUCYNTA® ER. Consider the use of alternative nonopioid analgesics in these patients.

Study design:

In a prospective, randomized, double-blind, active- and placebo-controlled, multicenter phase 3 study, subjects with moderate to severe chronic low back pain (N=981) were selected to evaluate the efficacy and safety of NUCYNTA® ER. Subjects were randomized in a 1:1:1 ratio to receive controlled, adjustable doses of NUCYNTA® ER (100-250 mg bid), oxycodone CR (20-50 mg bid), or placebo bid. This study was designed with a dose ratio of 5:1 for NUCYNTA® ER to oxycodone CR. Therefore, 100 mg to 250 mg of NUCYNTA® ER and 20 mg to 50 mg oxycodone CR were studied. The study was not designed to establish equianalgesic doses. Oxycodone CR was included for analgesic assay sensitivity and not as a head-to-head comparator. The study consisted of a screening period, a washout period, a 15-week treatment period (3-week double-blind titration period followed by a 12-week double-blind maintenance period), and a follow-up period. No breakthrough medication was allowed for low back pain during maintenance period. The primary efficacy endpoint was change from baseline in mean pain intensity at Week 12 on the Numerical Rating Scale. The co-primary efficacy endpoint was change from baseline in mean pain intensity over the entire 12-week maintenance period.1

NUCYNTA® ER: WELL-DEFINED SAFETY1

When a patient no longer requires therapy with NUCYNTA® ER tablets, use a gradual downward titration of the dose to prevent signs and symptoms of withdrawal in the physically dependent patient

WARNINGS AND PRECAUTIONS: WITHDRAWAL SYMPTOMS REPORTED AFTER ABRUPT DISCONTINUATION OF TREATMENT WITH NUCYNTA® ER WITHOUT TAPERING IN A CHRONIC LOW BACK PAIN STUDY1
Chart showing significantly low instances of withdrawals with NUCYNTA® ER Study Design +
  • Assessment: Opioid-like withdrawal symptoms were assessed using the Clinical Opiate Withdrawal Scale (COWS)* questionnaire, which was completed at follow-up with patients who discontinued study treatment
    • Patients completed a COWS questionnaire on Day 1, Days 2 to 5, or 5 days after treatment cessation
    • When discontinuing NUCYNTA® ER, gradually taper the dose

*The COWS is a clinician-rated 11-item scale that primarily evaluates the physical components of opioid withdrawal and is based on questions and clinical observations.

Responses are rated on a scale ranging from 0-4 (or 5, depending on item). Total scores range from 0‑48 with high scores indicating more severe symptoms of opioid withdrawal.

WARNINGS AND PRECAUTIONS: Avoidance of Withdrawal:

Withdrawal symptoms (e.g., anxiety, sweating, insomnia, restlessness, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection) may occur:

  • After abrupt discontinuation or a significant dose reduction of NUCYNTA® ER in physically dependent patients. When discontinuing NUCYNTA® ER, gradually taper the dose.
  • If mixed agonist/antagonist (e.g., butorphanol, nalbuphine, pentazocine) and partial agonist (e.g., buprenorphine) analgesics are used in patients who have received or are receiving NUCYNTA® ER. Avoid use with mixed agonists/antagonists and partial agonists.
  • If opioid antagonists (e.g., naloxone, nalmefene) are administered in physically dependent patients. Administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.

Study design:

In a prospective, randomized, double-blind, active- and placebo-controlled, multicenter phase 3 study, subjects with moderate to severe chronic low back pain (N=981) were selected to evaluate the efficacy and safety of NUCYNTA® ER. Subjects were randomized in a 1:1:1 ratio to receive controlled, adjustable doses of NUCYNTA® ER (100-250 mg bid), oxycodone CR (20-50 mg bid), or placebo bid. This study was designed with a dose ratio of 5:1 for NUCYNTA® ER to oxycodone CR. Therefore, 100 mg to 250 mg of NUCYNTA® ER and 20 mg to 50 mg oxycodone CR were studied. The study was not designed to establish equianalgesic doses. Oxycodone CR was included for analgesic assay sensitivity and not as a head-to-head comparator. The study consisted of a screening period, a washout period, a 15-week treatment period (3-week double-blind titration period followed by a 12-week double-blind maintenance period), and a follow-up period. No breakthrough medication was allowed for low back pain during maintenance period. The primary efficacy endpoint was change from baseline in mean pain intensity at Week 12 on the Numerical Rating Scale. The co-primary efficacy endpoint was change from baseline in mean pain intensity over the entire 12-week maintenance period.1

References
  1. Buynak R, Shapiro DY, Okamoto A, et al. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase Ill study. Expert Opin Pharmocother. 2010;11(11):1787-1804.
  2. OxyContin® [package insert]. Stamford, CT: Purdue Pharma LP; 2010.
  3. Data on file. Depomed, Inc; 2008 (cLBP).