Efficacy and safety of prucalopride in patients with chronic idiopathic constipation stratified by age, body mass index, and renal function: a post hoc analysis of phase III and IV, randomized, placebo-controlled clinical studies.

BACKGROUND

Prucalopride (1 or 2 mg once daily) is approved for treating adults with chronic idiopathic constipation (CIC).

OBJECTIVES

We determined the effect of age, body mass index (BMI), and renal function on the efficacy and safety of prucalopride in adults with CIC.

DESIGN

Data were pooled from six 12-week, phase III-IV clinical studies in adults who received prucalopride (1 or 2 mg once daily) or placebo for CIC.

METHODS

Adults were stratified by age (<50; 50-64; ⩾65 years), BMI (underweight/healthy weight, <25 kg/m2; overweight, 25 to <30 kg/m2; obese, ⩾30 kg/m2), and renal function (normal renal function, estimated glomerular filtration rate (eGFR) ⩾90 mL/min/1.73 m2; mild renal impairment, eGFR 60 to <90 mL/min/1.73 m2; moderate renal impairment, eGFR 30 to <60 mL/min/1.73 m2). The primary efficacy endpoint was the proportion of patients with a mean of ⩾3 complete spontaneous bowel movements/week over 12 weeks. Safety data were evaluated descriptively.

RESULTS

Of 2484 patients stratified by age (prucalopride, n = 1237; placebo, n = 1247), 1402, 708, and 374 were aged <50, 50-64, and ⩾65 years, respectively. Of 2482 patients stratified by BMI (prucalopride, n = 1237; placebo, n = 1245), 1425, 713, and 344 were underweight/healthy weight, overweight, and obese, respectively. Of 2474 patients stratified by renal function (prucalopride, n = 1233; placebo, n = 1241), 1444, 869, and 161 had normal renal function, mild renal impairment, and moderate renal impairment, respectively. More prucalopride-treated than placebo-treated patients achieved the primary efficacy endpoint. The difference was significant for all subgroups, except for the obese and moderate renal impairment subgroups. More prucalopride-treated than placebo-treated patients reported treatment-related adverse events in most subgroups.

CONCLUSION

Prucalopride demonstrated efficacy in adults with CIC, irrespective of age, BMI, and renal function. No unexpected safety concerns were identified.

TRIAL REGISTRATION: ClinicalTrials.gov identifiers (https://clinicaltrials.gov/): NCT01147926, NCT01424228, NCT01116206, NCT00483886, NCT00485940, NCT00488137.