Forest publishes data from pivotal Phase III Study of Investigational FDC of nebivolol and valsartan

May 31 2014

Forest Laboratories, Inc. (NYSE:FRX) today announced the publication of data from its pivotal Phase III Study of an Investigational Fixed-Dose Combination (FDC) of nebivolol and valsartan in the May 30, 2014 issue of The Lancet. In the study, the combination of nebivolol and valsartan met its primary and key secondary endpoints, demonstrating statistically significant reductions from baseline in diastolic and systolic blood pressure vs. both nebivolol alone and valsartan alone at 8 weeks in patients with hypertension.

"These data indicate that the combinations of nebivolol and valsartan were effective at lowering blood pressure in patients with hypertension," said Thomas Giles, M.D., Professor of Medicine, Tulane University School of Medicine. "To our knowledge, this is the first study to assess the efficacy and safety of a fixed-dose combination consisting of a beta-blocker and angiotensin II receptor blocker in hypertensive patients. The data from this trial show that the combination provided significantly greater blood pressure reductions vs. nebivolol monotherapy and vs. valsartan monotherapy with treatment-emergent adverse events that were similar across all treatment groups, including placebo."

The mean change in trough seated diastolic blood pressure from baseline to week 8 for FDC 20/320 mg was significantly greater vs. valsartan 320 mg, the highest approved valsartan dose (-15.7 ± 9.6 mmHg vs. -11.2 ± 9.3 mmHg; least squares mean difference (LSMD) [95% CI]: -4.4 [-5.4, -3.3] mmHg, P<0.001) and significantly greater vs. nebivolol 40 mg, the highest approved nebivolol dose (-15.7 ± 9.6 mmHg vs. -14.4 ± 9.4 mmHg; LSMD [95% CI]: -1.2 [-2.3, -0.1] mmHg,>

The baseline-to-endpoint decrease in trough seated systolic blood pressure was significantly greater FDC 20/320 mg vs. valsartan 320 mg: -17·8 ± 15·8 mmHg vs. -14.8 ± 15.1 mmHg; LSMD [95% CI]: -3.1 [-4.9, -1.4] mmHg, P<0.001 and FDC 20/320 mg vs. nebivolol 40 mg: -17.8 ± 15.8 mmHg vs. -15.1 ± 16.5 mmHg; LSMD [95% CI]: -2.9 [-4.7, -1.1] mmHg, P=0.001. All other FDC doses were also significantly better than monotherapies at week 8, (all p<0.01). Other nebivolol and valsartan fixed-dose combinations examined (FDC 5/80 mg, FDC 5/160 mg) resulted in significantly greater reductions from baseline in diastolic and systolic blood pressure at week 4, except for FDC 5/160 mg vs. valsartan 160 mg on systolic blood pressure.

Across all FDC doses the most common adverse reactions (incidence ≥ 2% and greater than that observed in the placebo group) were fatigue (0.9% to 2.3% vs. 1.1% in placebo), and dizziness (1.6% to 2.3% vs. 0.4% in placebo).

Study Design

This pivotal 8-week randomized, double-blind, placebo-controlled clinical trial in 4,161 hypertension patients studied nebivolol 5, 10, 20, and 40mg and valsartan 80, 160, and 320mg alone and in various fixed-dose combinations. The study consisted of a 1-week screening period, followed by 6 weeks of placebo wash-out, an 8-week double-blind treatment period, and a 1-week down-titration period. During the double-blind treatment period, patients were initially randomized to one of eight treatment groups: FDC nebivolol/valsartan 5/80, 5/160, or 10/160mg; nebivolol 5 or 20mg; valsartan 80 or 160mg or placebo. After four weeks, all dosages were doubled.

Source: Forest Laboratories