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: Risk from Concomitant Use with Benzodiazepines or Other CNS Depressants:

Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on NUCYNTA ER therapy. The co-ingestion of alcohol with NUCYNTA ER may result in increased plasma tapentadol levels and a potentially fatal overdose of tapentadol. Profound sedation, respiratory depression, coma, and death may result from the concomitant use of NUCYNTA ER with benzodiazepines or other CNS depressants (e.g., non‑benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

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<sup>®</sup> 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:

Risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

The use of NUCYNTA ER in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: NUCYNTA ER-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of NUCYNTA ER.

Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Alternatively, consider the use of non-opioid analgesics in these patients.

Monitor such patients closely, particularly when initiating and titrating NUCYNTA ER and when NUCYNTA ER is 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<sup>®</sup> 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, a Schedule II controlled substance. As an opioid, NUCYNTA ER exposes users to the risks of addiction, abuse, and misuse. Because extended-release products such as NUCYNTA ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of tapentadol present.

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed NUCYNTA ER. Addiction can occur at recommended doses and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing NUCYNTA ER, and monitor all patients receiving NUCYNTA ER for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the prescribing of NUCYNTA ER for the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as NUCYNTA ER, but use in such patients necessitates intensive counseling about the risks and proper use of NUCYNTA ER 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:

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death.

Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status.

Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of NUCYNTA ER, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression especially within the first 24-72 hours of initiating therapy with and following dosage increases of NUCYNTA ER.

To reduce the risk of respiratory depression, proper dosing and titration of NUCYNTA ER are essential. Overestimating the NUCYNTA ER dosage when converting patients from another opioid product can result in fatal overdose with the first dose.

Accidental ingestion of even one dose of NUCYNTA ER, especially by children, can result in respiratory depression and death due to an overdose of tapentadol.

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. Collegium Pharmaceutical, Inc. (DPN).