TY - JOUR
T1 - Prucalopride induces high-amplitude propagating contractions in the colon of patients with chronic constipation
T2 - a randomized study
AU - Miner, P. B.
AU - Camilleri, M.
AU - Burton, D.
AU - Achenbach, H.
AU - Wan, H.
AU - Dragone, J.
AU - Mellgard, B.
N1 - Publisher Copyright:
© 2016 Shire Development LLC Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Background: This study compared prucalopride, a selective, prokinetic, 5-HT4 receptor agonist, with polyethylene glycol 3350 + electrolytes (PEG3350), an osmotic laxative, on colonic motility parameters, primarily high-amplitude propagating contractions (HAPCs) in patients with chronic constipation. Methods: This randomized, cross-over, reader-blinded study was conducted at a single site in the USA. The study was open to men and women aged 18–75 years who met study inclusion criteria. Colonic manometry catheters were inserted the day before investigation. On the investigation days, patients received oral 2 mg prucalopride or 2 × 13.8 g PEG3350 in solution. The primary endpoint was HAPC count (threshold: mean amplitude ≥100 mmHg, propagation ≥20 cm [HAPC1]) in the 12 h after treatment administration. Analyses were also conducted at two co-primary thresholds: mean amplitude ≥75 mmHg, propagation ≥20 cm (HAPC2); and mean amplitude ≥75 mmHg, propagation ≥10 cm (HAPC3). Secondary endpoints included HAPC area under the curve (AUC), contraction force, amplitude, duration, and propagation velocity. Key Results: Thirteen women were enrolled, with 12 completing the study. Significantly more HAPC1 (8.7 ± 2.06 vs 2.9 ± 2.06; p = 0.012) and HAPC2 (9.0 ± 2.11 vs 3.3 ± 2.11; p = 0.017) were observed in the 12-h periods with prucalopride than with PEG3350. Prucalopride significantly increased mean propagation distance and velocity (HAPC2) and mean AUC, force, and amplitude (HAPC3) compared with PEG3350. Adverse events were mild or moderate. Conclusions & Inferences: Prucalopride was superior to PEG3350 in inducing HAPCs in patients with chronic constipation. ClinicalTrials.gov number NCT01707667.
AB - Background: This study compared prucalopride, a selective, prokinetic, 5-HT4 receptor agonist, with polyethylene glycol 3350 + electrolytes (PEG3350), an osmotic laxative, on colonic motility parameters, primarily high-amplitude propagating contractions (HAPCs) in patients with chronic constipation. Methods: This randomized, cross-over, reader-blinded study was conducted at a single site in the USA. The study was open to men and women aged 18–75 years who met study inclusion criteria. Colonic manometry catheters were inserted the day before investigation. On the investigation days, patients received oral 2 mg prucalopride or 2 × 13.8 g PEG3350 in solution. The primary endpoint was HAPC count (threshold: mean amplitude ≥100 mmHg, propagation ≥20 cm [HAPC1]) in the 12 h after treatment administration. Analyses were also conducted at two co-primary thresholds: mean amplitude ≥75 mmHg, propagation ≥20 cm (HAPC2); and mean amplitude ≥75 mmHg, propagation ≥10 cm (HAPC3). Secondary endpoints included HAPC area under the curve (AUC), contraction force, amplitude, duration, and propagation velocity. Key Results: Thirteen women were enrolled, with 12 completing the study. Significantly more HAPC1 (8.7 ± 2.06 vs 2.9 ± 2.06; p = 0.012) and HAPC2 (9.0 ± 2.11 vs 3.3 ± 2.11; p = 0.017) were observed in the 12-h periods with prucalopride than with PEG3350. Prucalopride significantly increased mean propagation distance and velocity (HAPC2) and mean AUC, force, and amplitude (HAPC3) compared with PEG3350. Adverse events were mild or moderate. Conclusions & Inferences: Prucalopride was superior to PEG3350 in inducing HAPCs in patients with chronic constipation. ClinicalTrials.gov number NCT01707667.
KW - 5-HT receptor
KW - constipation
KW - dihydrobenzofuran-carboxamide
KW - polyethylene glycol
KW - prokinetic
KW - prucalopride
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U2 - 10.1111/nmo.12832
DO - 10.1111/nmo.12832
M3 - Article
C2 - 27270968
AN - SCOPUS:84983516615
SN - 1350-1925
VL - 28
SP - 1341
EP - 1348
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
IS - 9
ER -