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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

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
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

Aims: Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1-adrenoceptor agonist, in the treatment of faecal incontinence. Methods: Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. Discussion: This is the first randomised controlled study to investigate the efficacy and safety of a selective α1-adrenoceptor agonist for the treatment of faecal incontinence. Furthermore, this is the first time the impact of NRL001 on assessments of QoL, health outcomes and patient satisfaction will be assessed. Innovative strategies were developed to meet the challenge of recruiting patients for this study, for example, media advertising, posters and mailshots as allowed by each study centre.

α-adrenoceptor agonist, Faecal incontinence, Libertas study, NRL001
1462-8910
59-66
Siproudhis, L.
f99fb89f-1811-43ed-b025-6b25c44d7dae
Jones, D.
9e71197f-77c1-4151-8e61-c2e52a2e30a7
Shing, R. Ng Kwet
877cf83f-fa37-4e37-975e-4f13e52e4c16
Walker, D.
b94e6f46-ec02-4b5b-a726-67c0aafc9f94
Scholefield, J. H.
12aa924c-a29b-4a3c-bb9e-3b5fb9247dae
Scholefield, John
da4a2c61-d046-41e7-8388-97121c78617f
Brown, Stephen
b4aaf64c-2032-4715-a9ea-ef5e604b5de1
Espin, Eloy
8dd2b1f9-6407-4661-b20b-36b5121a419e
Herold, Alexander
b861bdc9-5673-4298-8436-ce3e5555ed2f
Jayne, David
ac68590a-ccc5-4b29-972a-39d502f4a5a1
Lenisa, Leonardo
4816680c-45b9-4466-bbe9-33f0b08833c9
Marti, Lukas
49672c76-2f80-43cc-a200-d0eec37c11e5
Scherer, Roland
48e0cf31-df05-4c88-8e8d-82585b42f8f6
Schwandner, Oliver
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Stuto, Angelo
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Nugent, Karen
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Camm, John
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Wexner, Steven
cedd3370-97ab-4a34-9c32-06954c37bfa7
Vaizey, Caroline
2b0408bd-dcd6-4d35-ac5a-b388df24d75d
Gruss, Hans Juergan
99782035-910e-4dff-afc1-32ec3401e132
Turner, Jackie
2b4328ec-91e8-45a7-a593-f30f86cf2a40
Siproudhis, L.
f99fb89f-1811-43ed-b025-6b25c44d7dae
Jones, D.
9e71197f-77c1-4151-8e61-c2e52a2e30a7
Shing, R. Ng Kwet
877cf83f-fa37-4e37-975e-4f13e52e4c16
Walker, D.
b94e6f46-ec02-4b5b-a726-67c0aafc9f94
Scholefield, J. H.
12aa924c-a29b-4a3c-bb9e-3b5fb9247dae
Scholefield, John
da4a2c61-d046-41e7-8388-97121c78617f
Brown, Stephen
b4aaf64c-2032-4715-a9ea-ef5e604b5de1
Espin, Eloy
8dd2b1f9-6407-4661-b20b-36b5121a419e
Herold, Alexander
b861bdc9-5673-4298-8436-ce3e5555ed2f
Jayne, David
ac68590a-ccc5-4b29-972a-39d502f4a5a1
Lenisa, Leonardo
4816680c-45b9-4466-bbe9-33f0b08833c9
Marti, Lukas
49672c76-2f80-43cc-a200-d0eec37c11e5
Scherer, Roland
48e0cf31-df05-4c88-8e8d-82585b42f8f6
Schwandner, Oliver
94600c1f-b83b-44d3-bde2-2446d94a7895
Stuto, Angelo
54d9ed43-379f-4172-b8c8-191f40f9cc33
Nugent, Karen
79fcb89d-6ff2-47b8-ac2c-2afb24954456
Camm, John
2224a858-84e1-4af0-a1a5-52d969b8cbcd
Wexner, Steven
cedd3370-97ab-4a34-9c32-06954c37bfa7
Vaizey, Caroline
2b0408bd-dcd6-4d35-ac5a-b388df24d75d
Gruss, Hans Juergan
99782035-910e-4dff-afc1-32ec3401e132
Turner, Jackie
2b4328ec-91e8-45a7-a593-f30f86cf2a40

Siproudhis, L., Jones, D., Shing, R. Ng Kwet, Walker, D., Scholefield, J. H., Scholefield, John, Brown, Stephen, Espin, Eloy, Herold, Alexander, Jayne, David, Lenisa, Leonardo, Marti, Lukas, Scherer, Roland, Schwandner, Oliver, Stuto, Angelo, Nugent, Karen, Camm, John, Wexner, Steven, Vaizey, Caroline, Gruss, Hans Juergan and Turner, Jackie (2014) 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. Colorectal Disease, 16 (S1), 59-66. (doi:10.1111/codi.12546).

Record type: Article

Abstract

Aims: Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1-adrenoceptor agonist, in the treatment of faecal incontinence. Methods: Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. Discussion: This is the first randomised controlled study to investigate the efficacy and safety of a selective α1-adrenoceptor agonist for the treatment of faecal incontinence. Furthermore, this is the first time the impact of NRL001 on assessments of QoL, health outcomes and patient satisfaction will be assessed. Innovative strategies were developed to meet the challenge of recruiting patients for this study, for example, media advertising, posters and mailshots as allowed by each study centre.

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More information

Published date: 11 February 2014
Keywords: α-adrenoceptor agonist, Faecal incontinence, Libertas study, NRL001

Identifiers

Local EPrints ID: 444805
URI: http://eprints.soton.ac.uk/id/eprint/444805
ISSN: 1462-8910
PURE UUID: 4ff8d658-71d3-4450-bc53-882b79c853e8

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Date deposited: 05 Nov 2020 17:31
Last modified: 07 Jan 2022 23:32

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Contributors

Author: L. Siproudhis
Author: D. Jones
Author: R. Ng Kwet Shing
Author: D. Walker
Author: J. H. Scholefield
Author: John Scholefield
Author: Stephen Brown
Author: Eloy Espin
Author: Alexander Herold
Author: David Jayne
Author: Leonardo Lenisa
Author: Lukas Marti
Author: Roland Scherer
Author: Oliver Schwandner
Author: Angelo Stuto
Author: Karen Nugent
Author: John Camm
Author: Steven Wexner
Author: Caroline Vaizey
Author: Hans Juergan Gruss
Author: Jackie Turner

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