NUCYNTA® ER: ONE SOURCE OF RELIEF FOR CHRONIC LOW BACK PAIN1

Powerful efficacy in reducing mean pain intensity vs placebo

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

IMPROVEMENT IN MEAN PAIN INTENSITY AT WEEK 15 IN A CHRONIC LOW BACK PAIN STUDY1

Chart showing improvement in mean pain intensity at week 15 from baseline as measured by NRS

  • Primary efficacy endpoint: Change in mean pain intensity from baseline to Week 15 (Week 12 of the maintenance phase) as measured by the 11-point Numerical Rating Scale (NRS)*
  • Primary efficacy analysis: Based on the last observation carried forward (LOCF) imputation method. Treatment comparisons used ANCOVA model and were based on least squares mean difference from placebo
  • Mean baseline pain intensity score: 7.5
  • Average daily dose in the maintenance phase
    • NUCYNTA® ER: 357 mg to 393 mg
    • Oxycodone CR: 67 mg to 75 mg

Oxycodone CR is the opioid ingredient in OxyContin®.
OxyContin® is a registered trademark of Purdue Pharma LP.2
*An 11-point pain intensity scale, with a score of 0 being "no pain" and a score of 10 being "pain as bad as you can imagine."

WARNINGS AND PRECAUTIONS: Interactions With Central Nervous System Depressants:

Hypotension, profound sedation, coma, respiratory depression, and death may result if NUCYNTA® ER is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, tranquilizers, general anesthetics, neuroleptics, other opioids). When considering the use of NUCYNTA® ER in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. If the decision to begin NUCYNTA® ER is made, start with NUCYNTA® ER 50 mg every 12 hours, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant.

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: Improvements in Patient‑Reported Outcomes

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

SECONDARY EFFICACY ENDPOINT, SF-36, IN A CHRONIC LOW BACK PAIN STUDY1
Chart showing NUCYNTA® ER versus Placebo and Oxycodone CR versus Placebo Data represent LSMD (least squares mean difference) vs placebo.
Adapted from Buynak et al.

Study Design +
  • Secondary efficacy endpoints: Short Form-36 (SF-36) survey evaluating 8 dimensions of health completed at baseline and at Weeks 1, 5, 9, and 12

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

WARNINGS AND PRECAUTIONS: Use in Elderly, Cachectic, or Debilitated Patients:

Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance. Because elderly patients are more likely to have decreased renal and hepatic function, consideration should be given to starting elderly patients in the lower range of recommended doses. Closely monitor these patients, particularly when initiating and titrating NUCYNTA® ER and when given concomitantly with other drugs that depress respiration.

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: ONE SOURCE OF RELIEF FOR THE PAIN ASSOCIATED WITH DIABETIC PERIPHERAL NEUROPATHY (DPN)3

The powerful efficacy of NUCYNTA® ER was maintained over 12 weeks vs placebo

CHANGE IN MEAN PAIN INTENSITY SCORES THROUGH THE END OF OPEN‑LABEL AND DOUBLE‑BLIND PHASES OF A 15-WEEK DPN STUDY3
Chart showing efficacy of NUCYNTA® ER was maintained over 12 weeks vs placebo Adapted from Schwartz et al.
  • Primary efficacy endpoint: Change in mean pain intensity over the last week of the double-blind maintenance phase as measured by the 11-point Numerical Rating Scale (NRS)*
  • Primary efficacy analysis: Based on the last observation carried forward (LOCF) imputation method and the intent-to-treat (ITT) population
  • Mean baseline pain intensity score:
    • 3-week open-label (OL) phase: 7.3
    • 12-week double-blind (DB) phase: 3.5

*An 11-point pain intensity scale, with a score of 0 being "no pain" and a score of 10 being "pain as bad as you can imagine."

WARNINGS AND PRECAUTIONS: Addiction, Abuse, and Misuse:

NUCYNTA® ER contains tapentadol, an opioid agonist and a Schedule II controlled substance that can be abused in a manner similar to other opioid agonists, legal or illicit. There is a greater risk for overdose and death due to the larger amount of tapentadol present in NUCYNTA® ER. Assess risk for opioid abuse or addiction prior to prescribing NUCYNTA® ER. Addiction can occur in patients appropriately prescribed NUCYNTA® ER at recommended doses; in those who obtain the drug illicitly; and if the drug is misused or abused. Therefore, routinely monitor for signs of misuse, abuse, and addiction. Patients at increased risk (e.g., patients with a personal or family history of substance abuse or mental illness) may be prescribed NUCYNTA® ER, but use in such patients necessitates intensive counseling about the risks and proper use along with intensive monitoring for signs of addiction, abuse, and misuse.

Study design:

In a double-blind, parallel-group, enriched-enrollment randomized phase 3 study, subjects with chronic DPN were selected to assess the efficacy and safety of NUCYNTA® ER. The study had a 3-week open-label phase (N=588) during which all subjects were titrated to their individual dose of NUCYNTA® ER 100-250 mg bid. That was followed by a 12-week double-blind maintenance phase (N=389) during which subjects were randomized 1:1 to continue taking NUCYNTA® ER or receive placebo. Supplemental analgesia was permitted. The primary efficacy endpoint was the change from baseline in mean pain intensity over Week 12 of the maintenance period.3

NUCYNTA® ER: Improvements in patient-reported outcomes3

More than 64% of DPN patients reported overall pain status was “very much improved” or “much improved”

PATIENTS REPORTING OVERALL STATUS "VERY MUCH IMPROVED" OR "MUCH IMPROVED" AT THE END OF A 15-WEEK DPN STUDY3
Chart showing more than 64% of DPN patients reported overall pain status was 'very much improved' or 'much improved' Adapted from Schwartz et al.

Study Design +

  • Secondary efficacy endpoint: Patient's global impression of change (PGIC) at Weeks 2, 6, and 12 of the double-blind phase as measured by a 7-point verbal rating scale*

*Patients rated their response to the statement, "Since I began study medication, my overall status is, "with a numerical range from 1 ("very much improved") to 7 ("very much worse").

WARNINGS AND PRECAUTIONS: Life-threatening Respiratory Depression:

Can occur at any time during the use of NUCYNTA® ER even when used as recommended. Respiratory depression from opioid use, if not immediately recognized and treated, may lead to respiratory arrest and death. To reduce the risk of respiratory depression, proper dosing and titration are essential. Overestimating the dose when converting patients from another opioid product can result in fatal overdose with the first dose. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status.

Study design:

In a double-blind, parallel-group, enriched-enrollment randomized phase 3 study, subjects with chronic DPN were selected to assess the efficacy and safety of NUCYNTA® ER. The study had a 3-week open-label phase (N=588) during which all subjects were titrated to their individual dose of NUCYNTA® ER 100-250 mg bid. That was followed by a 12-week double-blind maintenance phase (N=389) during which subjects were randomized 1:1 to continue taking NUCYNTA® ER or receive placebo. Supplemental analgesia was permitted. The primary efficacy endpoint was the change from baseline in mean pain intensity over Week 12 of the maintenance period.3

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. Schwartz S, Etropolski M, Shapiro DY, et al. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial. Curr Med Res Opin. 2011;27(1):151-162.
  4. Data on file. Depomed, Inc; 2008 (DPN).