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

Abstract

Administration of NRL001 suppositories led to decreases in HR when compared with placebo data. NRL001 was well tolerated with a good safety profile during the study. Healthy elderly subjects did not show significantly different biological responses to NRL001 suppositories compared with younger healthy volunteers in previous studies.

Meta‐analysis for cardiovascular effects of NRL001 after rectal application in healthy volunteers

“…A number of studies have been conducted with NRL001 in healthy volunteers. Four studies—SUM (NCT00857467) , SURD (NCT01099670) , SUSD (NCT00850590) and SAGE (NCT01099683) —used a similar study design to assess the pharmacokinetics, pharmacodynamics and safety of NRL001 versus placebo, using NRL001 rectal suppositories in healthy volunteers. Data from these four trials were assessed to quantify the effect of NRL001 on cardiovascular safety parameters.…”

Faecal incontinence: the ‘Cinderella’ disorder

“…In the SAGE study , healthy elderly subjects received a single 2 g suppository of 10 mg NRL001 and a matching placebo in two separate treatment periods. They did not show significantly different biological responses to NRL001 than seen in younger healthy volunteers in the earlier studies.…”

“…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…”

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].…”