Novartis has provided a safety update to European regulators of pooled data showing numerically less frequent liver enzyme elevations in patients who took either 50 mg per day or 50 mg twice daily of Galvus ( Vildagliptin ) compared to 100 mg once-daily. As a result, Novartis has proposed changes to European prescribing information recommending use of the already-approved 50 mg once-daily and twice-daily doses instead of the 100 mg once-daily dose.
An updated analysis of pooled clinical trial data involving more than 8,000 patients treated with Galvus was finalized following the European Union approval and included recently completed studies.
The recent analysis further characterized a known imbalance in liver enzyme levels, which now appears more visibly in the higher Galvus once-daily dosing regimen. The results showed 0.86% of Galvus patients taking the 100 mg once-daily dose, 0.34% of those taking the 50 mg twice-daily dose and 0.21% of those taking the 50 mg once-daily dose had elevations of the liver enzymes aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) of greater than three times the upper limit of normal ( 3xULN ).
At a 50 mg daily dosage, the incidence rate was comparable to the 0.20% in the pooled comparator group of about 4,400 patients taking Metformin, a thiazolidinedione, a sulfonylurea or a placebo. The placebo rate was 0.40%, and this was numerically higher than the Galvus 50 mg twice-daily dose. Elevated levels of these enzymes can indicate liver cell damage.
Galvus is a member of a new drug class known as DPP-4 inhibitors.
The currently approved European information recommends a 50 mg once-daily dose for use in combination with a sulfonylurea as well as a 50 mg twice-daily or 100 mg once-daily dose for combination use with either Metformin or a thiazolidinedione.
The results of a new clinical study, published in the journal Diabetes, Obesity and Metabolism, further confirmed the efficacy of Galvus in combination with Metformin, a long-standing oral type 2 diabetes treatment.
This trial showed Galvus was as effective as Pioglitazone ( Actos ), a member of the thiazolidinedione class of diabetes medicines, when each was combined with metformin. Galvus was well tolerated and did not cause the weight gain that often occurs in patients taking a thiazolidinedione.
In the 24-week study of 576 patients with type 2 diabetes, all of whom had inadequately controlled diabetes despite taking Metformin, the addition of a 50 mg twice-daily dose of Galvus to Metformin treatment reduced blood sugar levels as effectively as adding a 30 mg once-daily dose of Pioglitazone to Metformin.
Galvus was shown to be weight neutral, while the addition of the thiazolidinedione was associated with weight gain ( up to 1.9 kg after 24 weeks of treatment ).
Source: Novartis, 2007