Analgesic - bicifadine
Chronic pain remains extremely difficult to manage, despite the plethora of analgesic agents already on the market. Many of these have significant drawbacks for patients, such as dose limiting adverse events, a danger of developing tolerance to the drugs, and a risk of becoming dependent on them. Add to this the fact that some forms of pain prove difficult to overcome, and the need for non-addictive, side-effect-free analgesics that are effective against the most intractable forms of pain becomes obvious.
Chronic pain remains extremely difficult to manage, despite the plethora of analgesic agents already on the market. Many of these have significant drawbacks for patients, such as dose limiting adverse events, a danger of developing tolerance to the drugs, and a risk of becoming dependent on them. Add to this the fact that some forms of pain prove difficult to overcome, and the need for non-addictive, side-effect-free analgesics that are effective against the most intractable forms of pain becomes obvious.
Another non-opioid analgesic is being developed by DOV Pharmaceuticals, under licence from Wyeth. Bicifadine inhibits both the norepinephrine and serotonin transporters, and also acts as an N-methyl-D-aspartate (NMDA) antagonist with a non-narcotic profile.1 Numerous clinical trials have been carried out that show its potential as an analgesic.
In one single dose, double blind, parallel group trial controlled to both placebo and aspirin, 100 patients with moderate to severe postoperative abdominal or orthopaedic pain were given 75 or 150mg of bicifadine orally, placebo, or 650mg aspirin. It was well tolerated, and significant analgesia was seen in the patients given the higher dose, compared with all three of the other treatment arms.2
A double blind, randomised, placebo controlled single dose Phase II trial was carried out in 752 patients. It compared bicifadine's efficacy and safety with placebo and codeine in postoperative dental pain. Subjects were given 200, 400 or 600mg of bicifadine, 60mg codeine, or placebo in oral doses. Those given the new drug gained better pain relief than those given placebo; a significant time-related improvement in pain release for the two highest doses, with maximum effects seen within two or three hours of dosing; and the pain relief given by the 600mg dose was better than codeine.3
Phase III trials are also being carried out, and results of one have been reported.4 A total of 540 patients were included in the double blind, randomised, placebo controlled single dose trial, which compared the efficacy of bicifadine in doses of 200, 400 and 600mg with placebo and 100mg doses of tramadol in subjects with moderate to severe postoperative dental pain.
Again, the drug was well tolerated, and no serious adverse events were experienced, with the major problems being nausea and emesis. Those given bicifadine had the best pain control, with maximum effects being seen an hour after dosing. These maximal effects for the two highest doses were similar to those obtained with tramadol.