Top-Line Results With Novel Chronic Pain Drug Positive

Megan Brooks

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August 26, 2011 — Zogenix, Inc, has announced positive top-line results from a pivotal phase 3 efficacy study of its extended-release capsule formulation of hydrocodone bitartrate (Zohydro).

The product is novel, in that it does not contain acetaminophen.

"If approved, Zohydro could be the first extended-release hydrocodone treatment available without acetaminophen, which is associated with an increased risk of liver toxicity when used in high doses over time," the company notes in a statement.

Study 801 Meets Primary End Point

The drug is being evaluated for the treatment of moderate to severe chronic pain in patients requiring 24-hour opioid therapy for an extended period.

In Study 801, the drug met the primary end point by providing significantly better pain relief (P = .008) compared with placebo, the company reported.

Study 801 was a multicenter, randomized, double-blind, placebo-controlled study involving more than 300 opioid-experienced adults with inadequately controlled moderate to severe chronic lower back pain.

The trial consisted of an open-label conversion and titration phase of the new agent followed by a 12-week placebo-controlled treatment phase comparing Zohydro 20 to 100 mg every 12 hours to placebo.

The primary efficacy endpoint was the mean change from baseline to the end of 12 weeks of treatment in the average 24-hour pain intensity ratings based on the 0 to 10 Numerical Rating Scale from daily electronic diaries comparing the drug and placebo.

Results "Encouraging"

In addition to providing significantly better pain relief than placebo, the study also met 2 key secondary endpoints: the proportion of patients with at least 30% improvement in pain intensity and an improvement of overall satisfaction with the medication.

The drug was safe and well tolerated. The most commonly reported adverse events in patients treated with this formulation (>5%) were constipation, nausea, and urinary tract infection.

"We are very encouraged by the study results, which we believe are meaningful for patients suffering from moderate to severe chronic pain," Stephen J. Farr, PhD, Zogenix president and chief operating officer, said in a prepared statement.

"Zohydro will offer hydrocodone for the first time in a convenient 12-hour dose while eliminating acetaminophen," Dr. Farr noted. The new formulation "may simplify physicians' ability to prescribe the appropriate hydrocodone dose for chronic pain while managing the inadvertent overuse of acetaminophen, which is a common ingredient in combination pain products and over-the-counter medications," he added.

Zogenix plans to submit a new drug application for this product to the US Food and Drug Administration by early 2012.

FDA Approves Tapentadol for Chronic Pain

Allison Gandey

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August 26, 2011 — The US Food and Drug Administration (FDA) has approved tapentadol extended release (Nucynta, Janssen Pharmaceuticals) for moderate to severe chronic pain.

The drug, already approved for acute pain, has now been given the okay for long-term use, the company announced today. In Europe, tapentadol is marketed as Palexia.

The drug is a centrally acting synthetic analgesic. The oral mu-opioid agonist is taken twice daily in adults when a continuous, around-the-clock analgesic is needed for an extended period of time. Tapentadol extended release is not intended for use on an as-needed basis.

It is classified as schedule II of the Controlled Substances Act and carries risks for abuse similar to those of other opioids. Working with the FDA, Janssen has developed a risk evaluation and mitigation strategy for tapentadol.

The strategy, which is similar to those developed for other medications in this category, is designed to educate prescribers about the potential for abuse, addiction, and overdose.

Janssen says it also plans to monitor for inappropriate use of its products.

Chronic pain is the most common cause of long-term disability; almost one third of Americans will reportedly experience chronic pain at some point in their lives.

Despite the treatments available, the American Pain Society says additional options are still needed to help patients manage their pain.

"Chronic pain is difficult to manage, and even with the treatments available today, it can be a challenge to balance pain relief with a patient's ability to tolerate the medicine," Sunil Panchal, MD, president of the National Institute of Pain, said in a news release. "People with chronic pain will continue to need additional options, so an approval like this is welcome news for this community and the people who suffer from this often debilitating condition."

The most common adverse reactions, appearing in at least 10% of patients, were nausea, constipation, headache, dizziness, and somnolence.

Life-Threatening Serotonin Syndrome

Respiratory depression is the primary risk for mu-opioid agonists. They can also raise cerebrospinal fluid pressure and should not be used in patients who may be susceptible to the effects, such as those with evidence of head injury and increased intracranial pressure.

Tapentadol extended release has not been evaluated in patients with a predisposition to a seizure disorder.

The product is also contraindicated in patients who are receiving monoamine oxidase inhibitors or who have taken them within the last 14 days because of potential additive effects on norepinephrine levels, which may result in adverse cardiovascular events.

Cases of life-threatening serotonin syndrome have been reported with the concurrent use of tapentadol and serotonergic drugs. This includes serotonin reuptake inhibitors; serotonin and norepinephrine reuptake inhibitors; tricyclic antidepressants; triptans; drugs that affect the serotonergic neurotransmitter system, such as mirtazapine, trazodone, and tramadol; and drugs that impair metabolism of serotonin.

Complete product information is available online.