Pain Therapeutics Inc. moved one step closer to providing relief to backache sufferers as it began a pivotal trial of Oxytrex for chronic pain.

The 700-patient study is designed to evaluate the painkiller's ability to treat chronic, severe low-back pain. Its primary efficacy endpoint, a measure of reduction in pain relative to oxycodone and placebo, follows on findings from a 21-day Phase II study that showed a statistically significant reduction when using Oxytrex vs. the comparator arms.

"For us to have achieved clinical and statistical significance against oxycodone is a big, big deal, because what it really says is that we have an opportunity to shift the market away from oxycodone and into Oxytrex," Pain Therapeutics President and CEO Remi Barbier told BioWorld Today, noting that annual U.S. sales of oxycodone total about $1.5 billion. "Based on this design, we have been ready to push the button on a Phase III study that actually is very similar to the Phase II, except that it's twice as big and includes patients with lower-back pain - the second leading cause of severe pain, after osteoarthritic pain."

The South San Francisco-based company is studying Oxytrex, a combination of immediate-release oxycodone and low-dose naltrexone, in a different indication in order to file for FDA approval of a broad label. Barbier said Pain Therapeutics could file for the osteoarthritic pain indication given the Phase II data, which pointed to Oxytrex's superiority over oxycodone (p=0.006) and placebo (p<0.001).

"But we are one of the few, if not the only, pain company that has written guidance from the FDA that says if we show the safety and efficacy of our drug in several different models of pain, we will be granted broad-label approval," he added. "From a market perspective, that means you can pretty much market these drugs wherever and however they're used today."

The company, which Barbier said would burn about $17 million this year, developed OxyTrex as a substitute for oxycodone and other moderately strong opioids. The randomized, double-blinded, placebo-controlled Phase III study is designed to compare the analgesic effects seen in the three arms over a three-month treatment period, though patient enrollment in the U.S.-based trial could take up to a year.

"We really developed Oxytrex the old-fashioned way," Barbier said. "We started with some very novel biological observations. We then worked with physiological models, animals, single-dose human studies and then multiple-dose efficacy studies. It requires a lot more patience than the more modern way, but it works."

He declined to specify dosing details of the study, though he noted that oxycodone is approved for use four times a day, and that could be excessive. Pain Therapeutics, which reported a cash position of about $46 million through March 31, has patent applications still pending relative to dosing. Early this year, the company entered a partnership to develop a longer-acting formulation with Cupertino, Calif.-based Durect Corp. (See BioWorld Today, Jan. 15, 2003.)

Elsewhere in its pipeline is PTI-901, another drug candidate the company is positioning for a $1 billion or more market. Designed to treat pain associated with irritable bowel syndrome, recent data have shown it works in men and women with either constipation or diarrhea. Barbier said Pain Therapeutics would begin a 600-700 patient study late this year.

"We plan to hold onto our drugs for as long as we can, and certainly through a new drug application," he said. "This is a game of patience and building slow economic value, and that entire economic value gets converted into tremendous upside immediately upon approval."

A sales and marketing partnership will come along, he added, "as soon as we see the right economics from the right pharmaceutical partners."

Barbier added that the company is keeping details of its next product under wraps until this year's fourth quarter. Development of another narcotic painkiller, MorViva (formerly called PTI-555/501), has been slowed as Pain Therapeutics focuses on its late-stage opportunities. The modified formulation of morphine would likely find use in an emergency care setting, he said.

Pain Therapeutics' shares (NASDAQ:PTIE) gained 57 cents Monday, or 9.7 percent, to close at $6.45.