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Randomised clinical trial: study of escalating doses of NRL 001 given in rectal suppositories of different weights
Author(s) -
Bell D.,
Pediconi C.,
Jacobs A.
Publication year - 2014
Publication title -
colorectal disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.029
H-Index - 89
eISSN - 1463-1318
pISSN - 1462-8910
DOI - 10.1111/codi.12542
Subject(s) - suppository , medicine , placebo , pharmacokinetics , adverse effect , gastroenterology , area under the curve , anesthesia , urology , pharmacology , alternative medicine , pathology
Aims The application of α‐adrenoceptor agonists can improve faecal incontinence symptoms. The aim of this study was to investigate the pharmacokinetic and systemic effects of NRL 001 administered as different strengths in 1 or 2 g suppositories. Methods This randomised, double‐blind, placebo controlled study included 48 healthy subjects. Group 1 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 5, 7.5 or 10 mg NRL 001, or matching placebo. Group 2 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 10, 12.5 or 15 mg NRL 001, or matching placebo. Doses were given in an escalating manner with placebo at a random position within the sequence. Results T max was at ~4.5 h post‐dose for all NRL 001 doses. Median AUC 0–tz , AUC 0–∞ and C max increased with increasing dose for both suppository sizes. The estimate of ratios of geometric means comparing 2 g with 1 g suppository, and regression analysis for dose proportionality, was close to 1 for the variables AUC 0–tz , AUC 0–∞ and C max ( P > 0.05). For both suppository sizes, 20‐min mean pulse rate was significantly decreased compared with placebo with all doses ( P < 0.05). Blood pressure decreased overall. There were 144 adverse events ( AE s) and no serious AE s reported during the study. All AE s were mild in severity. Conclusions The regression analysis concluded that the doses were dose proportional.