Raritan, N.J., May 17, 2012 -- Janssen Pharmaceuticals, Inc. today announced the results of an investigational Phase 3 study suggesting NUCYNTA® ER (tapentadol) extended-release tablets were significantly more effective than placebo in providing pain management among adults with chronic moderate to severe, painful diabetic peripheral neuropathy (DPN). Results of the study were presented at the 31st Annual Scientific Meeting of the American Pain Society being held May 16-19 in Honolulu, Hawaii.
Diabetes affects nearly 26 million people in the United States1 - and its prevalence is expected to grow significantly during the coming decades.2 Over time, people with diabetes can develop a type of nerve damage called neuropathy. Approximately 60 to 70 percent of people with diabetes have some form of neuropathy.3 The most common type is diabetic peripheral neuropathy, which causes pain or loss of feeling in the toes, feet, legs, hands, and arms.
The study found, among patients who had at least a one-point reduction in pain intensity during three weeks of treatment with tapentadol ER, those who continued on an optimized dose of tapentadol ER (100-250 mg twice daily) for an additional 12 weeks experienced significantly better pain control compared to those who switched to placebo.4 Treatment-emergent adverse events reported in 10 percent or more of tapentadol ER-treated patients during the double-blind maintenance period included nausea (21.1 percent) and vomiting (12.7 percent).4
"Painful DPN is a common and burdensome complication of diabetes, and controlling pain in people with DPN can be challenging," said Aaron I. Vinik, M.D., Ph.D., FCP, MACP, Director of Research and Neuroendocrine Unit at Strelitz Diabetes Center for Endocrine and Metabolic Disorders at Eastern Virginia Medical School, and lead investigator of the study. "These data suggest tapentadol ER provides a significant reduction in chronic pain in adult patients with DPN."
The findings of this study are consistent with those of another Janssen-sponsored study published early last year, which found tapentadol ER to be effective versus placebo for relieving moderate to severe chronic pain associated with diabetic peripheral neuropathy.
"We are pleased the Phase 3 data presented today showed tapentadol ER was effective at providing pain management for patients with chronic, moderate to severe pain associated with DPN," said Christine Rauschkolb, M.D., Ph.D., Vice President and Head of Integrated Operations, Janssen Research & Development, LLC and one of the study's authors. "Janssen has a long history of helping physicians provide responsible treatment for patients to relieve their acute and chronic pain. We are committed to developing new pain management options for the millions of Americans who have painful DPN."
About the Study
This Phase 3 clinical trial was a randomized-withdrawal, placebo-controlled study. It enrolled adult patients who had moderate to severe, chronic painful DPN for six months or more and a history of analgesic use for painful DPN for three months or more. This trial had three phases: an open-label phase, which included a 3-week titration period during which the individually optimized tapentadol ER dose (100-250 mg two times per day) was determined for each patient; a 12-week, double-blind maintenance phase, during which patients with a one-point or greater reduction in pain intensity from beginning to end of titration were randomized either to continue taking tapentadol ER (at their optimal dose) or to receive placebo; and a follow-up period with a clinic visit at four days and a telephone interview at 10 to 14 days after discontinuation of study drug.
The primary efficacy endpoint of the study was the mean change in average pain intensity from baseline (point of randomization) to the last week of the 12-week, double-blind maintenance phase, as determined by an 11-point pain rating scale or numerical rating scale (NRS; 0='no pain,' 10='pain as bad as you can imagine'). Safety assessments were performed on the open-label and double-blind safety populations (all patients who received ?1 dose of open-label and double-blind treatment, respectively). Treatment-emergent adverse events (TEAEs), defined as any AEs (new or worse in intensity) that occurred after the first intake of study drug during the open-label or double-blind phase, were monitored throughout the study.
In the open-label titration period, 459 patients received one or more doses of tapentadol ER and were included in the open-label safety population. At the start of the 3-week, open-label phase, the majority of patients (87.1 percent) reported severe pain (6 or more on the 11-point NRS) with a mean pain intensity of 7.3. By the end of the open-label phase, the mean pain intensity was reduced to 3.6. Treatment-emergent adverse events (TEAEs) experienced by 10 percent or more of patients during the open-label phase were nausea (24.4 percent), dizziness (17), constipation (11.8) and somnolence (10.7).
A total of 358 patients completed the open-label titration period; 318 were randomized and received one or more dose of study medication (n=152 for placebo, 166 for tapentadol ER).
Following randomization, during the double-blind treatment phase to week 12, pain increased in the placebo group (as demonstrated by the mean change in pain intensity of 1.3), while in the tapentadol ER group, efficacy was maintained, as indicated by the mean change in pain intensity of 0.28. The least-squares mean difference between the tapentadol ER and placebo groups in the change in average pain intensity was -0.95 on the 11-point NRS favoring tapentadol ER (95 percent CI, -1.42 to -0.49; p<0.001, tapentadol ER vs. placebo).4
For more details about the study design, please visit www.clinicaltrials.gov (NCT01041859).
Janssen Research & Development, LLC and Grünenthal GmbH, conducted this study, which Janssen Research & Development, LLC has included as part of its Supplemental New Drug Application (sNDA) submitted on October 28, 2011 to the U.S. Food and Drug Administration (FDA) for tapentadol ER tablets for the management of neuropathic pain associated with DPN in patients 18 years of age or older. The FDA currently is reviewing this supplemental application.
About Tapentadol and NUCYNTA® ER
Tapentadol is a centrally-acting synthetic analgesic. The tapentadol molecule is classified as Schedule II of the Controlled Substances Act.
NUCYNTA® ER (tapentadol) extended-release tablets are an oral analgesic available by prescription only and indicated for the management of moderate to severe chronic pain in adults when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. NUCYNTA® ER is taken twice daily and available in 50 mg, 100 mg, 150 mg, 200 mg and 250 mg strengths.
Outside the United States, tapentadol is marketed by Janssen Inc. in Canada; Grünenthal GmbH discovered tapentadol and markets immediate- and extended-release formulations of tapentadol (PALEXIA®) in various countries in Europe.
IMPORTANT SAFETY INFORMATION FOR NUCYNTA® ER (tapentadol) extended-release tablets
WARNING: POTENTIAL FOR ABUSE, PROPER PATIENT SELECTION, AND LIMITATIONS OF USE
Potential for Abuse
NUCYNTA® ER contains tapentadol, a mu-opioid agonist and a Schedule II controlled substance with an abuse liability similar to other opioid analgesics.
NUCYNTA® ER can be abused in a manner similar to other opioid agonists, legal or illicit. These risks should be considered when prescribing or dispensing NUCYNTA® ER in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Schedule II opioid substances, which include hydromorphone, morphine, oxycodone, fentanyl, oxymorphone, and methadone, have the highest potential for abuse and risk of fatal overdose due to respiratory depression.
Proper Patient Selection
NUCYNTA® ER is an extended-release formulation of tapentadol indicated for the management of moderate to severe chronic pain in adults when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.
Limitations of Use
NUCYNTA® ER is not intended for use as an as-needed analgesic.
NUCYNTA® ER is not intended for the management of acute or postoperative pain.
NUCYNTA® ER tablets are to be swallowed whole and are not to be split, broken, chewed, dissolved, or crushed. Taking split, broken, chewed, dissolved, or crushed NUCYNTA® ER tablets could lead to rapid release and absorption of a potentially fatal dose of tapentadol.
Patients must not consume alcoholic beverages, or prescription or nonprescription medications containing alcohol. Co-ingestion of alcohol with NUCYNTA® ER may result in a potentially fatal overdose of tapentadol.
NUCYNTA® ER is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma or hypercapnia in unmonitored settings or in the absence of resuscitative equipment.
WARNINGS & PRECAUTIONS
About Janssen Pharmaceuticals, Inc. and Janssen Research and Development, LLC
At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop and bring innovative products, services and solutions to people throughout the world.
Janssen Pharmaceuticals, Inc., and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies.
Janssen Pharmaceuticals, Inc. provides medicines for an array of health concerns in several therapeutic areas. Innovative therapies Janssen Pharmaceuticals, Inc. offers currently include ACIPHEX® (rabeprazole sodium), DORIBAX® (doripenem for injection), ELMIRON® (pentosan polysulfate sodium), NUCYNTA® (tapentadol), NUCYNTA® ER (tapentadol) extended-release tablets and XARELTO® (rivaroxaban) tablets. The full prescribing information for NUCYNTA® ER, including boxed warnings, is available here; the full prescribing information for XARELTO®, including boxed warnings, is available here.
For more information on Janssen Research & Development, LLC, visit us at http://www.janssenrnd.com/.
* Dr. Vinik was compensated for his work as a clinical investigator in the clinical trials for NUCYNTA® ER.