Phosphagenics delivers further positive morphine results

A phase Ib clinical trial of Melbourne-based Phosphagenics' (ASX:POH, AIM:PSG) TPM-01 transdermal delivery system has demonstrated that therapeutic levels of morphine in plasma were achieved and maintained for more than 48 hours using the technology.

The results mirror those achieved in a phase Ia study of TPM-01 and morphine to test tolerability and safety which were announced in April 2005.

"With the two studies together we've got approximately 28 patients who've all responded, which is fairly good for a phase I," said Phosphagenics' executive director of research and development, Dr Esra Ogru.

The phase Ib study was conducted over a week at the Royal Adelaide Hospital with a single dose of non-invasive gel -- containing TPM-01 and about 100 mg of morphine -- being applied to the outer upper arm of 18 patients. TPM-01 is a highly phosphorylated molecule that conjugates readily to both small and large molecule drugs, enabling their delivery through the skin into the bloodstream.

The randomised study, which examined the pharmacokinetics (PK) of the patients, showed therapeutic blood morphine levels within two hours. These levels were maintained for over 48 hours with full clearance by 72 hours. Ogru said there were no side effects reported from the trial to date.

Phosphagenics now plans to seek approval for a phase IIa study expected to commence in the first quarter of 2006 to assess the efficacy of TPM-01 and morphine for relief of post-operative pain.

"It will be a fairly large study, probably between 35-45 patients in total," said Ogru. "We're looking at a clinic where there are a lot of sport injuries, people who have just had their operation, come out, and put on the formulation and see how they deal with pain. We'll take blood at the same time for PK testing."

Oral administration of morphine produces dose spiking and side effects such as constipation, nausea and drowsiness. There is currently no commercially available transdermal morphine product. Extended-release forms of morphine are safer, and produce fewer side-effects, but the only extended-release formulations currently available are oral products, and are effective for only 12 to 24 hours per dose. Phosphagenics' transdermal formulation, applied via a skin patch, could double this interval.

Another benefit of TPM-01, said Ogru, is that it is not delivered through a typical patch but by formulation. "Once you've applied the formulation to the skin, it forms a reservoir under the skin. So you can go and shower and you can swim," she said.

Patient compliance is also improved using transdermal application, said Ogru, "it's easier, people much prefer to do that than take six tablets a day."

Phosphagenics has also recently shown that its TPM-01 technology can be applied to fentanyl, the only opioid pain killer which is currently on the market in a transdermal form. Phosphagenics plans to offer fentanyl and morphine to prospective commercial partners as part of a portfolio of transdermal pain products.

"We're in good discussions at the moment with some international big players for morphine and any other pain products," said Ogru. "We're trying to develop a pain franchise. It's not just morphine, anything that's out there used to control pain, we can deliver."

Ogru said that the company is in the early stages of studying oxycontin and hydromorphone with TPM-01.

Phosphagenics has previously demonstrated transdermal delivery using TPM-01 as a carrier of the heart drug atropine, the hormones estradiol and testosterone, and large molecules such as insulin and parathyroid hormone.

The company hopes to follow its phase IIa morphine study with a large protein or insulin trial, said Ogru.

Phosphagenics' TPM-01/Morphine research is 50 per cent funded through a $1.7 million R&D Start grant from AusIndustry.