A double‐blind, placebo‐controlled, randomised, parallel‐group, dose‐escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days

Abstract

Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect.

A randomised, controlled, crossover study to investigate the pharmacodynamics, pharmacokinetics and safety of 1R,2S‐methoxamine hydrochloride (NRL001) in healthy elderly subjects

“…NRL001 is associated with a dose‐dependent effect on anal sphincter tone resulting in increases in mean anal resting pressure (MARP), supporting its potential therapeutic use in faecal incontinence . NRL001 suppositories have also been shown to be well tolerated in healthy subjects in repeated daily doses up to 15 mg . Increasing NRL001 concentrations were associated with decreased heart rate (HR) in Phase I studies in healthy volunteers .…”

“…NRL001 suppositories have also been shown to be well tolerated in healthy subjects in repeated daily doses up to 15 mg . Increasing NRL001 concentrations were associated with decreased heart rate (HR) in Phase I studies in healthy volunteers .…”

Libertas: rationale and study design of a multicentre, Phase II, double–blind, randomised, placebo–controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence

“…NRL001 has also demonstrated an excellent safety profile in preclinical (Norgine, data on file) and Phase I clinical trials. [21][22][23][24].…”

Faecal incontinence: the ‘Cinderella’ disorder

“…NRL001 is undertaking its journey through this complex process and this supplement describes the early Phase I work together with a meta-analysis of the cardiovascular data from these studies; see Table 1 for a list of the studies reported [25][26][27][28][29]. In addition, the Phase II clinical study design is presented [30].…”

“…This suggests that NRL001 is worthy of clinical investigation in Phase II patient populations with passive faecal incontinence. [25] A randomised, controlled, crossover study to investigate the safety and response of 1R,2S-methoxamine hydrochloride (NRL001) on anal function in healthy volunteers SUSD [26] Randomised clinical trial: study of escalating doses of NRL001 given in rectal suppositories of different weights SAGE [27] A randomised, controlled, crossover study to investigate the pharmacodynamics, pharmacokinetics and safety of 1R,2S-methoxamine hydrochloride (NRL001) in healthy elderly subjects SURD [28] A double-blind, placebo-controlled, randomised, parallel-group, doseescalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days Meta-analysis [29] Meta-analysis for cardiovascular effects of NRL001 after rectal application in healthy volunteers…”