Patients receiving Pain Therapeutics Inc.'s opioid painkiller Oxytrex experienced the same pain relief but reported less physical dependence and fewer side effects than those taking oxycodone, according to the first of two Phase III studies.

The trial, which enrolled 719 patients with severe, chronic lower-back pain, compared Oxytrex (oxycodone formulated with ultra-low-dose naltrexone) to oxycodone. Results indicated that Oxytrex patients "reported about 50 percent less symptoms of physical dependence and withdrawal after cessation of high-dose opioid use, compared to patients on oxycodone," said Remi Barbier, president and CEO of Pain Therapeutics, during a conference call to discuss the Phase III trial Thursday.

In addition, patients receiving Oxytrex reported fewer opioid-related side effects during treatment, including somnolence, pruritus and moderate to severe constipation.

"We're obviously very, very pleased with these results," Barbier said. "We have a lot of data that signifies that we really do have a better drug here than oxycodone."

The Phase III trial was designed as a superiority study. Barbier explained that the primary endpoint was to determine whether Oxytrex was superior in efficacy to oxycodone by providing greater pain relief or providing the same pain relief with less-frequent dosing, fewer side effects or fewer withdrawal symptoms.

Patients in the study all suffered persistent pain for more than six months. They began with a four- to 10-day wash-out period before being divided into four groups. One group received twice-daily dosing of Oxytrex, a second group received Oxytrex four times per day, the third group was treated with oxycodone, and the fourth group received placebo. Barbier said the first six weeks of the trial was a self-titration period, during which the patients would receive escalating doses of Oxytrex, up to 80 mg, until they reported adequate pain relief, as measured as a two out of 10 on the Likert Pain Scale, with zero representing no pain and 10 being the worst pain.

Following the self-titration portion of the study, patients' doses were fixed for the next three months. At the end of the study, physical dependence was measured using the Short Opiate Withdrawal Scale (SOWS). The twice-daily Oxytrex group reported lower mean SOWS scores (1.2) than patients in the oxycodone group (2.6) in the first 24 hours following drug discontinuation.

"As far as we know, this is the first study to demonstrate significant and minimal withdrawal effects after prolonged opioid use," Barbier said.

The company attributes the reduction in dependency and withdrawal to the product's mechanism of action. Opioid drugs, which activate inhibitory signals through opioid receptors, provide analgesia by dulling the transmission of pain signals to the brain. But they also activate the excitatory signals to provoke the adverse effects of dependence, tolerance and addiction.

Barbier said Oxytrex combines the opioid painkiller with naltrexone, an opioid antagonist, designed to help minimize those effects.

The Oxytrex and oxycodone groups in the study all outperformed the placebo group, reporting about equal pain relief - an average 45 percent reduction in pain intensity from baseline scores.

But Barbier said the dosing levels presented a pleasant surprise.

"The key here is that patients on Oxytrex reported those pain scores using substantially and statistically significantly less dose of drugs," he said. Oxytrex patients' average dosing levels were 35 mg vs. the 39 mg needed by patients in the oxycodone group.

Pain Therapeutics is conducting a second Phase III trial with Oxytrex, in about 700 patients with moderate to severe osteoarthritic pain. Patients receive a fixed dose of drug (either 20 mg per day or 40 mg per day of Oxytrex, oxycodone or placebo) for three months. Results are expected around the end of the year, and if the data appear to be similar to the first trial, the company said it would begin discussing plans for a new drug application.

In addition to Oxytrex, South San Francisco-based Pain Therapeutics has two other pain products in Phase III trials. Barbier said results from a study of PTI-901 in irritable bowel syndrome will be reported this year, and a second study, specifically in women, just completed enrollment. Remoxy, the company's product for severe chronic pain, is expected to begin a second Phase III trial soon, while results from the first trial are expected sometime this year.

Pain Therapeutics' shares (NASDAQ:PTIE) gained 7 cents Thursday to close at $5.94.