Merck & Co., which is developing a diet drug that works by blocking the CB-1 receptor like Sanofi's diet pill Acomplia (rimonabant), has begun a Phase III trial of its drug based on a dosage far lower than what Sanofi is trying to get approved by the U.S. Food and Drug Administration.

While Sanofi is seeking approval of a 20 mg dose of rimonabant, and Pfizer is testing a CB-1 receptor antagonist that seems to work best at a 15 mg dosage, the highest dosage being tested in Merck's phase III trial is 2 mg.

Merck, in three Phase II studies still underway of the drug it now calls MK-0364, has been testing 2 mg, 4 mg and 6 mg dosages of the diet drug against a placebo with more than 5,600 participants.

It now has launched a Phase IIb/III trial involving about 1,000 participants -- 400 of whom are getting the 2 mg dose, with 200 getting a 1 mg dose, 200 getting a .5 mg dose, and 200 getting a placebo -- suggesting it has concluded that lower may be better.

Merck, which has had nothing to say publicly abouts its CB-1 receptor antagonist, was shown a copy of this story and declined comment.

But the consent forms Merck has had patients sign to participate in the Phase III trial state that dosages of MK-0364 ranging from .5 mg to 600 mg or a placebo have been given in various trials to more than 6,000 participants.

While most of these participants were in Phase II trials as short as 12 weeks and as long as two years, the number of patients involved in these studies gives Merck a body of experience with CB-1 receptor antagonists -- and their possible side-effects -- that rivals the clinical trial experience of Sanofi.

With Acomplia stalled at the FDA for reasons widely believed to be centered on concern over side effects, it is interesting to note that many of the side-effects for MK-0364 cited in the Merck consent form were similar to those reported for rimonabant -- nausea, mood-swings, anxiety and depression.

But several other side-effects reported by Merck are worth noting.

One patient, who as part of a dosing study apparently was given a single 100 mg dose of MK-0364, developed "a severe rash and itching, which are symptoms of Stevens-Johnson syndrome (severe rash with blister-like areas). This patient fully recovered after treatment with corticosteroid therapy. . ."

In the three ongoing studies of the 2 mg, 4 mg and 6 mg dosages of MK-0364, Merck said:

• "Four participants were diagnosed with depression and suicidal thoughts. The study doctors considered these diagnoses serious, severe, and related to the study drug."
• "Three participants had seizures. One of these participants had a history of surgery for a brain tumor; another participant had a history of seizures, and the third participant had no history of seizures."
• "Two participants have died. One participant died suddenly, and researchers believe an abnormal heart rhythm played a part in the death. The study doctor thought the death was 'possibly drug related.' The second participant died from a severe blood infection, which the study doctor thought was 'definitely not drug related.' "

Outreach: If you are one of those participating in the Merck MK-0364 trial, and would like to share your experiences with us on a totally confidential basis, we would welcome a report on your results to date. If we receive enough reports, we will incorporate them in a follow-up story. Please email your reports to info@AcompliaReport.com.