PMID- 24499493
OWN - NLM
STAT- MEDLINE
DCOM- 20141017
LR  - 20140206
IS  - 1463-1318 (Electronic)
IS  - 1462-8910 (Linking)
VI  - 16 Suppl 1
DP  - 2014 Mar
TI  - Randomised clinical trial: study of escalating doses of NRL001 given in rectal 
      suppositories of different weights.
PG  - 16-26
LID - 10.1111/codi.12542 [doi]
AB  - AIMS: The application of alpha-adrenoceptor agonists can improve faecal incontinence 
      symptoms. The aim of this study was to investigate the pharmacokinetic and 
      systemic effects of NRL001 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 NRL001, 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 NRL001, or matching placebo. Doses were given in an 
      escalating manner with placebo at a random position within the sequence. RESULTS: 
      Tmax was at ~4.5 h post-dose for all NRL001 doses. Median AUC0-tz , AUC0-infinity and 
      Cmax 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 AUC0-tz , 
      AUC0-infinity and Cmax (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 (AEs) and no 
      serious AEs reported during the study. All AEs were mild in severity. 
      CONCLUSIONS: The regression analysis concluded that the doses were dose 
      proportional.
CI  - Colorectal Disease (c) 2014 The Association of Coloproctology of Great Britain and 
      Ireland.
FAU - Bell, D
AU  - Bell D
AD  - Bio-Kinetic Europe Limited, Belfast, UK.
FAU - Pediconi, C
AU  - Pediconi C
FAU - Jacobs, A
AU  - Jacobs A
LA  - eng
SI  - ClinicalTrials.gov/NCT00850590
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Colorectal Dis
JT  - Colorectal disease : the official journal of the Association of Coloproctology of 
      Great Britain and Ireland
JID - 100883611
RN  - 0 (Adrenergic alpha-1 Receptor Agonists)
RN  - 0 (Suppositories)
RN  - HUQ1KC1YLI (Methoxamine)
SB  - IM
MH  - Adolescent
MH  - Adrenergic alpha-1 Receptor Agonists/*administration & dosage/adverse 
      effects/pharmacokinetics/pharmacology
MH  - Adult
MH  - Double-Blind Method
MH  - Fecal Incontinence/drug therapy
MH  - Female
MH  - Humans
MH  - Male
MH  - Methoxamine/*administration & dosage/adverse 
      effects/pharmacokinetics/pharmacology
MH  - Middle Aged
MH  - Suppositories/*administration & dosage/adverse 
      effects/pharmacokinetics/pharmacology
OTO - NOTNLM
OT  - Faecal incontinence
OT  - adrenergic alpha-agonists
OT  - methoxamine hydrochloride
OT  - rectal suppositories
EDAT- 2014/02/07 06:00
MHDA- 2014/10/18 06:00
CRDT- 2014/02/07 06:00
PHST- 2013/10/02 00:00 [received]
PHST- 2013/12/29 00:00 [accepted]
PHST- 2014/02/07 06:00 [entrez]
PHST- 2014/02/07 06:00 [pubmed]
PHST- 2014/10/18 06:00 [medline]
AID - 10.1111/codi.12542 [doi]
PST - ppublish
SO  - Colorectal Dis. 2014 Mar;16 Suppl 1:16-26. doi: 10.1111/codi.12542.