Randomized placebo-controlled clinical trial of a new chewable formulation of amlodipine for the treatment of hypertension in client-owned cats

BACKGROUND: There is an unmet clinical need for a cat‐specific formulation of amlodipine to treat hypertensive cats. OBJECTIVES: To assess the efficacy of chewable amlodipine tablets in reducing systolic blood pressure (SBP) in cats diagnosed with systemic arterial hypertension. ANIMALS: Seventy‐seven client‐owned cats with systemic hypertension were included (median age 14 years). METHODS: The study was randomized, double‐blinded, and placebo‐controlled. Forty‐two cats received 0.125–0.50 mg/kg amlodipine once daily for 28 days; 35 cats received placebo. After 28 days all cats continued with amlodipine for 2–3 months in an open‐label phase. Blood pressure was measured using high definition oscillometry. A responder was defined as a cat showing a decrease of SBP to <150 mmHg at 28 days or a decrease from baseline ≥15%. RESULTS: Sixty‐one cats completed the study. The responder rate was 63% in amlodipine group and 18% in placebo group. Cats receiving amlodipine were 7.9 (95% CI 2.6–24.1) times more likely to be classified as responders when compared to those receiving placebo (P < .001). From a mean (±SD) baseline value of 181 (±12) mmHg, SBP decreased to 154 (±17) mmHg with amlodipine and to 170 (±21) mmHg with placebo (P < .001). The voluntary acceptance rate of amlodipine formulation was 73%. CONCLUSIONS AND CLINICAL IMPORTANCE: The chewable amlodipine tablet effectively reduced SBP compared with placebo in hypertensive cats, and was well‐tolerated. It can be used concomitantly with angiotensin‐converting enzyme inhibitors and in cats with chronic kidney disease

Best practices during bioanalytical method validation for the characterization of assay reagents and the evaluation of analyte stability in assay standards, quality controls, and study samples

Characterization of the stability of analytes in biological samples collected during clinical studies together with that of critical assay reagents, including analyte stock solutions, is recognized as an important component of bioanalytical assay validation. Deficiencies in these areas often come to light during regulatory inspections. Best practices, based on current regulatory guidance, for the assessment of these issues as they pertain to ligand binding and chromatographic assays are covered in this review. Additionally, consensus recommendations reached during the recent AAPS/FDA Workshop on bioanalytical assay validation are highlighted