For the second time in the past six months, Pain Therapeutics Inc. is pushing a late-stage compound into a Phase III program.

The South San Francisco-based company began a pair of pivotal studies of PTI-901 (low-dose naltrexone HCI) in irritable bowel syndrome (IBS). The chronic abdominal disorder primarily affects women, who will make up half of the program's 1,200-patient enrollment.

Company officials were unavailable for comment, though in a press release Pain Therapeutics estimated that entry into a U.S. market of 20 million patients could represent a $1 billion opportunity.

Men and women will be evenly divided into two studies to be conducted at 80 U.S. sites. Aside from the gender split, the trials are identical - both are randomized, double-blinded, placebo-controlled studies designed to compare the clinical effects of PTI-901 against placebo during a three-month treatment period. The company expects enrollment to last about a year.

The trial will include patients with constipation-predominant, diarrhea-predominant or alternating symptoms of IBS. They will be evaluated for abdominal pain, bowel habits and stool consistency at baseline and during the treatment period. PTI-901 is the first in a new class of drugs designed to restore the balance of opioid activity in the gut, where an imbalance of such activity is believed to contribute to the disorder's symptoms.

Treatment consists of a single daily 0.5-mg oral dose of PTI-901 or placebo. The primary efficacy endpoint is relief of IBS symptoms, as measured by patients' observations of Subject Global Assessment of Relief. Secondary efficacy endpoints include improvements in abdominal pain, bloating, bowel habits and quality of life. Investigators also will evaluate safety through the assessment of various adverse events.

Prior success has encouraged Pain Therapeutics to advance the compound, to which it holds exclusive, worldwide commercial rights. Results from a 50-patient pilot study of PTI-901 in men and women reported at last month's American College of Gastroenterology meeting showed a 76 percent response rate to the drug, with no drug-related safety issues.

Pain Therapeutics plans to maintain full ownership of the compound through the new drug application stage, at which time it might consider partnering.

Another Phase III drug candidate to which it owns full rights, Oxytrex, is in a 700-patient pivotal study designed to evaluate the painkiller's ability to treat chronic, severe low-back pain. Early this year, the company entered a partnership to develop a longer-acting Oxytrex formulation with Cupertino, Calif.-based Durect Corp. (See BioWorld Today, Jan. 15, 2003, and July 1, 2003.)

A third candidate, Remoxy, is designed as an abuse-resistant, long-acting oxycodone.

Pain Therapeutics' stock (NASDAQ:PTIE) gained 26 cents Tuesday to close at $6.08.