Long-term safety and tolerability of valsartan in children aged 6 to 17 years with hypertension.

OBJECTIVE: The present study aimed to assess the long-term safety and tolerability of valsartan in hypertensive children aged 6-17 years, with or without chronic kidney disease (CKD). METHODS: This was an 18-month, open-label, multicentre, prospective study conducted in 150 patients with history of hypertension with or without CKD. The primary endpoint was long-term safety and tolerability of valsartan and valsartan-based treatments, assessed in terms of adverse events (AEs), serious AEs, laboratory measurements, estimated glomerular filtration rate (eGFR), urinalysis and electrocardiogram. RESULTS: Of 150 enrolled patients, 117 (78%) completed the study. At week 78, a clinically and statistically significant reduction in mean sitting systolic and diastolic blood pressures was observed in all patients (- 14.9 mmHg and - 10.6 mmHg, respectively). Within the first 3 months of treatment, mean urine albumin creatinine ratio decreased in CKD population, which was sustained. A higher percentage of CKD patients had at least one AE compared to non-CKD patients (85.3% vs. 73.3%, respectively). The majority of AEs were mild (50.7%) or moderate (18.7%) in severity. As expected, in patients with underlying CKD, increases in serum potassium, creatinine and blood urea nitrogen were more commonly reported compared to non-CKD patients. A > 25% decrease in Schwartz eGFR was observed in 28.4% of CKD patients and 13.5% of non-CKD patients. CONCLUSIONS: Valsartan was generally well tolerated, with an AE profile consistent with angiotensin receptor blockers in the overall population and in patients with underlying CKD. Long-term efficacy was maintained and a beneficial effect on proteinuria was observed.

Efficacy, Safety, and Systemic Exposure of Once-Daily Indacaterol Acetate in Pediatric Asthma: A Randomized, Double-Blind, Controlled Dose-Finding Study.

BACKGROUND: Indacaterol acetate (IND), a long-acting ß2-agonist in combination with mometasone furoate (MF), an inhaled corticosteroid (ICS), is being explored as a once-daily (od) treatment for asthma in children. This study examined the efficacy, safety, and systemic exposure of IND 75 µg and IND 150 µg in children with persistent asthma. METHODS: In this Phase IIb, multicenter, randomized, double-blind, parallel-group study, pediatric patients (aged ≥ 6 to < 12 years) with persistent asthma were randomized (1:1) to receive either IND 75 µg od or IND 150 µg od via Breezhaler® in combination with ICS background therapy. The primary endpoint was change from baseline in pre-dose trough forced expiratory volume in one second (FEV1) after two weeks of treatment. RESULTS: In total, 80 patients received IND 75 µg (n = 39) or IND 150 µg (n = 41). The study met its primary endpoint; both doses demonstrated improvements in pre-dose trough FEV1 from baseline to Day 14 (mean change [Δ]: 212 mL, IND 75 µg; 171 mL, IND 150 µg). The secondary spirometry parameters (post-dose FEV1 after 1-h, post-dose forced vital capacity; morning and evening peak expiratory flow) also improved. Overall, 36.1% in IND 75 µg group and 25% patients in IND 150 µg group achieved a decrease from baseline in Pediatric Interviewer-administered Asthma Control Questionnaire score of ≥ 0.5 units. A dose-dependent increase in plasma IND concentration was noted between the two groups. Both IND doses demonstrated an acceptable safety profile. CONCLUSIONS: Once-daily IND 75 µg and IND 150 µg via Breezhaler® in combination with background ICS therapy provided substantial bronchodilation in children with asthma and were well tolerated. Taken together, these clinical and systemic exposure findings support IND 75 µg as the most appropriate dose for evaluation in Phase III trials in combination with MF in pediatric asthma. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02892019; 08-Sep-2016).

Efficacy and safety of valsartan in children aged 1-5 years with hypertension, with or without chronic kidney disease: a randomized, double-blind study followed by open-label phase.

OBJECTIVE: To assess the dose-response relationship for reduction in mean systolic blood pressure (MSBP) with valsartan solution, in young children with hypertension with or without chronic kidney disease (CKD). METHODS: In this multicenter, randomized, double-blind, double-dummy study, 127 young children aged 1-5 years with hypertension (MSBP ≥95th percentile) were randomized (1:1) to receive valsartan 0.25 or 4 mg/kg/day for 6 weeks, followed by a 20 week open-label phase, where patients received valsartan 1 mg/kg/day for 4 weeks, and then optionally titrated to 2 mg/kg/day or up to 4 mg/kg/day. The primary endpoint was the change in MSBP from baseline at Week 6 during the double-blind phase. RESULTS: Overall, 120 patients (94.5%) completed the study; 63 had CKD. A clinically and statistically significant reduction in MSBP from baseline to Week 6 was observed with the valsartan 4 mg/kg group compared with the valsartan 0.25 mg/kg group (8.5 vs 4.1 mmHg; p = .0157). A positive dose-response relationship for MSBP reduction was observed between the 0.25 mg/kg and 4 mg/kg groups (p = .0012). In the CKD subgroup, a significant reduction in MSBP was observed with 4 mg/kg (9.2 mmHg) versus 0.25 mg/kg (1.2 mmHg; p = .0096). In the non-CKD subgroup, a numerically greater decrease in MSBP was observed with 4 mg/kg (7.8 mmHg) versus 0.25 mg/kg (6.9 mmHg; p = .6531). Incidence of adverse events was lower with valsartan 4 mg/kg than 0.25 mg/kg (41.9% vs 51.6%) and similar between CKD and non-CKD subgroups (48.4% vs 45.3%) irrespective of dose. Increase in serum potassium (>20% compared to baseline) was observed more frequently in patients with CKD compared to non-CKD patients. CONCLUSION: Valsartan was efficacious and well tolerated in children 1 to 5 years of age with hypertension, with or without CKD. Clinical trial registration: The study has been registered at ClinicalTrials.gov (Identifier: NCT01617681).