Forest Laboratories has reported positive topline results from a pivotal Phase III trial of nebivolol and valsartan combination therapy for the treatment of hypertension.
Meeting the primary endpoint, the investigational fixed dose combination (FDC) of nebivolol and valsartan demonstrated statistically significant reductions in diastolic blood pressure (DBP) compared to individual nebivolol and valsartan dosage at week eight.
The FDC also met the key secondary endpoint of change from baseline in systolic blood pressure (SBP) at week eight.
Forest Research Institute research and development senior vice president and president Marco Taglietti said the Phase III results in patients with Stage 1 or Stage 2 hypertension demonstrate the potential benefits of FDC beta blocker/ARB combination.
"We are very pleased with these results which demonstrate the efficacy and safety profile of this combination and support the potential use of the nebivolol/valsartan FDC as a new treatment option for patients with hypertension who need dual therapy to reach their blood pressure goals," Taglietti added.
Designed to meet the required regulatory ‘Combination Rule’, the pivotal nebivolol/valsartan FDC trial compared the FDC against the maximum approved dose of each component drug.
A total of 4,161 hypertension patients were randomised in the study to one of eight treatment groups including FDC nebivolol/valsartan 5/80mg, 5/160mg, or 10/160mg, nebivolol 5mg or 20mg, valsartan 80mg or 160mg or placebo.
Dosages were doubled after four weeks in the placebo-controlled trial comprising screening period of one week, placebo wash-out period of six weeks, a double-blind treatment period of eight weeks, and a one-week down-titration period.
Change from baseline in mean sitting trough DBP at eight weeks for FDC dose 20/320mg in opposition to nebivolol 40mg and against valsartan 320mg, and FDC doses 10/320mg and 10/160mg versus corresponding monotherapies is the study’s primary endpoint.
The combination demonstrated the incremental reduction in DBP of -1.2mm to -2.4mm Hg as compared to nebivolol and -3.7mm to -4.4mm Hg as compared to valsartan.
Across the doses of FDC 20/320mg, 10/320mg and 10/160mg compared to the same monotherapy components, the incremental reduction in SBP for the combination against nebivolol was -2.9mm to -3.6mm Hg and against valsartan was -3.0 to -3.9 mm Hg, meeting the key secondary endpoint.
FDC was well-tolerated at all doses and the most common adverse events were fatigue and dizziness.
The company plans to make the regulatory filing with the FDA for the combination therapy in the first quarter of 2014.