Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial

Research output: Contribution to journalJournal articleResearchpeer-review

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Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome : a randomised phase 2 trial. / Naimi, Rahim M; Hvistendahl, Mark; Enevoldsen, Lotte H; Madsen, Jan L; Fuglsang, Stefan; Poulsen, Steen Seier; Kissow, Hannelouise; Pedersen, Jens; Nerup, Nikolaj; Ambrus, Rikard; Achiam, Michael P; Svendsen, Lars B; Holst, Jens Juul; Hartmann, Bolette; Hansen, Svend H; Dragsted, Lars Ove; Steensberg, Adam; Mouritzen, Ulrik; Hansen, Mark B; Jeppesen, Palle Bekker.

In: The Lancet Gastroenterology and Hepatology, Vol. 4, No. 5, 2019, p. 354-363.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Naimi, RM, Hvistendahl, M, Enevoldsen, LH, Madsen, JL, Fuglsang, S, Poulsen, SS, Kissow, H, Pedersen, J, Nerup, N, Ambrus, R, Achiam, MP, Svendsen, LB, Holst, JJ, Hartmann, B, Hansen, SH, Dragsted, LO, Steensberg, A, Mouritzen, U, Hansen, MB & Jeppesen, PB 2019, 'Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial', The Lancet Gastroenterology and Hepatology, vol. 4, no. 5, pp. 354-363. https://doi.org/10.1016/S2468-1253(19)30077-9

APA

Naimi, R. M., Hvistendahl, M., Enevoldsen, L. H., Madsen, J. L., Fuglsang, S., Poulsen, S. S., ... Jeppesen, P. B. (2019). Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial. The Lancet Gastroenterology and Hepatology, 4(5), 354-363. https://doi.org/10.1016/S2468-1253(19)30077-9

Vancouver

Naimi RM, Hvistendahl M, Enevoldsen LH, Madsen JL, Fuglsang S, Poulsen SS et al. Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial. The Lancet Gastroenterology and Hepatology. 2019;4(5):354-363. https://doi.org/10.1016/S2468-1253(19)30077-9

Author

Naimi, Rahim M ; Hvistendahl, Mark ; Enevoldsen, Lotte H ; Madsen, Jan L ; Fuglsang, Stefan ; Poulsen, Steen Seier ; Kissow, Hannelouise ; Pedersen, Jens ; Nerup, Nikolaj ; Ambrus, Rikard ; Achiam, Michael P ; Svendsen, Lars B ; Holst, Jens Juul ; Hartmann, Bolette ; Hansen, Svend H ; Dragsted, Lars Ove ; Steensberg, Adam ; Mouritzen, Ulrik ; Hansen, Mark B ; Jeppesen, Palle Bekker. / Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome : a randomised phase 2 trial. In: The Lancet Gastroenterology and Hepatology. 2019 ; Vol. 4, No. 5. pp. 354-363.

Bibtex

@article{0ac9442dc2224b1da81692fb12fa5d17,
title = "Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial",
abstract = "Background: Patients with short bowel syndrome might have impaired postprandial endogenous glucagon-like peptide-2 (GLP-2) secretion, which is required for optimal intestinal adaptation. We aimed to assess the therapeutic potential of glepaglutide, a novel long-acting GLP-2 analogue, for reducing faecal output and increasing intestinal absorption in patients with short bowel syndrome.Methods: In this single-centre, double-blind, crossover, randomised phase 2 trial, adults (aged ≥18 to ≤90 years) with short bowel syndrome and with a faecal wet weight output of 1500 g/day or more were randomly assigned to receive one of six dose sequences of glepaglutide (10 mg, 1 mg; 10 mg, 0·1 mg; 1 mg, 10 mg; 1 mg, 0·1 mg; 0·1 mg, 10 mg; or 0·1 mg, 1 mg). Patients received daily subcutaneous injections of the first assigned dose of glepaglutide for 3 weeks, followed by a washout period of 4-8 weeks, and then the second dose of glepaglutide for 3 weeks. An unmasked statistician generated the randomisation list, and the trial investigator enrolled patients and assigned them their patient numbers. Trial investigators, patients, and other care providers were masked throughout the trial. The primary endpoint was the absolute change from baseline in faecal wet weight output, measured separately over the two treatment periods. Metabolic balance studies were done before and after each treatment period to assess the primary endpoint. Per-protocol analysis was used to assess the efficacy. Safety analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02690025, and has completed.Findings: Of the 22 patients screened between Feb 5, 2016, and Jan 25, 2017, 18 patients were randomly assigned and treated with glepaglutide; 16 patients completed the trial. Treatment with 1 mg and 10 mg glepaglutide changed the adjusted mean faecal output by -592 g/day (95{\%} CI -913 to -272; p=0·002) and -833 g/day (-1152 to -515; p=0·0002) from baseline, respectively. No changes were observed with 0·1 mg glepaglutide. Of the 18 patients who were randomly assigned to treatment, common treatment-related adverse events were stoma complications (13 [72{\%}] patients), injection site reactions (11 [61{\%}]), peripheral oedema (ten [56{\%}]), nausea and abdominal pain (eight [44{\%}] each), polyuria and fatigue (six [33{\%}] each), abdominal distention, vomiting, and dizziness (five [28{\%}] each); and cough and decreased appetite (four [22{\%}] each). Related or possibly related serious adverse events were reported in two patients in the 0·1 mg dose group and two patients in the 10 mg dose group. These events included abdominal pain, stoma obstruction, catheter-related sepsis, and infection of unknown origin. No patients died during the trial.Interpretation: Glepaglutide was well tolerated, and was associated with improved intestinal absorption in patients with short bowel syndrome with 1 mg and 10 mg glepaglutide, but not with 0·1 mg glepaglutide. Larger phase 3 clinical trials of longer durations have been initiated to fully assess the safety and efficacy of glepaglutide.Funding: Zealand Pharma.",
author = "Naimi, {Rahim M} and Mark Hvistendahl and Enevoldsen, {Lotte H} and Madsen, {Jan L} and Stefan Fuglsang and Poulsen, {Steen Seier} and Hannelouise Kissow and Jens Pedersen and Nikolaj Nerup and Rikard Ambrus and Achiam, {Michael P} and Svendsen, {Lars B} and Holst, {Jens Juul} and Bolette Hartmann and Hansen, {Svend H} and Dragsted, {Lars Ove} and Adam Steensberg and Ulrik Mouritzen and Hansen, {Mark B} and Jeppesen, {Palle Bekker}",
note = "CURIS 2019 NEXS 103 (Obs! Ingen fjernadgang!) Copyright {\circledC} 2019 Elsevier Ltd. All rights reserved.",
year = "2019",
doi = "10.1016/S2468-1253(19)30077-9",
language = "English",
volume = "4",
pages = "354--363",
journal = "The Lancet Gastroenterology and Hepatology",
issn = "2468-1253",
publisher = "Elsevier Limited",
number = "5",

}

RIS

TY - JOUR

T1 - Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome

T2 - a randomised phase 2 trial

AU - Naimi, Rahim M

AU - Hvistendahl, Mark

AU - Enevoldsen, Lotte H

AU - Madsen, Jan L

AU - Fuglsang, Stefan

AU - Poulsen, Steen Seier

AU - Kissow, Hannelouise

AU - Pedersen, Jens

AU - Nerup, Nikolaj

AU - Ambrus, Rikard

AU - Achiam, Michael P

AU - Svendsen, Lars B

AU - Holst, Jens Juul

AU - Hartmann, Bolette

AU - Hansen, Svend H

AU - Dragsted, Lars Ove

AU - Steensberg, Adam

AU - Mouritzen, Ulrik

AU - Hansen, Mark B

AU - Jeppesen, Palle Bekker

N1 - CURIS 2019 NEXS 103 (Obs! Ingen fjernadgang!) Copyright © 2019 Elsevier Ltd. All rights reserved.

PY - 2019

Y1 - 2019

N2 - Background: Patients with short bowel syndrome might have impaired postprandial endogenous glucagon-like peptide-2 (GLP-2) secretion, which is required for optimal intestinal adaptation. We aimed to assess the therapeutic potential of glepaglutide, a novel long-acting GLP-2 analogue, for reducing faecal output and increasing intestinal absorption in patients with short bowel syndrome.Methods: In this single-centre, double-blind, crossover, randomised phase 2 trial, adults (aged ≥18 to ≤90 years) with short bowel syndrome and with a faecal wet weight output of 1500 g/day or more were randomly assigned to receive one of six dose sequences of glepaglutide (10 mg, 1 mg; 10 mg, 0·1 mg; 1 mg, 10 mg; 1 mg, 0·1 mg; 0·1 mg, 10 mg; or 0·1 mg, 1 mg). Patients received daily subcutaneous injections of the first assigned dose of glepaglutide for 3 weeks, followed by a washout period of 4-8 weeks, and then the second dose of glepaglutide for 3 weeks. An unmasked statistician generated the randomisation list, and the trial investigator enrolled patients and assigned them their patient numbers. Trial investigators, patients, and other care providers were masked throughout the trial. The primary endpoint was the absolute change from baseline in faecal wet weight output, measured separately over the two treatment periods. Metabolic balance studies were done before and after each treatment period to assess the primary endpoint. Per-protocol analysis was used to assess the efficacy. Safety analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02690025, and has completed.Findings: Of the 22 patients screened between Feb 5, 2016, and Jan 25, 2017, 18 patients were randomly assigned and treated with glepaglutide; 16 patients completed the trial. Treatment with 1 mg and 10 mg glepaglutide changed the adjusted mean faecal output by -592 g/day (95% CI -913 to -272; p=0·002) and -833 g/day (-1152 to -515; p=0·0002) from baseline, respectively. No changes were observed with 0·1 mg glepaglutide. Of the 18 patients who were randomly assigned to treatment, common treatment-related adverse events were stoma complications (13 [72%] patients), injection site reactions (11 [61%]), peripheral oedema (ten [56%]), nausea and abdominal pain (eight [44%] each), polyuria and fatigue (six [33%] each), abdominal distention, vomiting, and dizziness (five [28%] each); and cough and decreased appetite (four [22%] each). Related or possibly related serious adverse events were reported in two patients in the 0·1 mg dose group and two patients in the 10 mg dose group. These events included abdominal pain, stoma obstruction, catheter-related sepsis, and infection of unknown origin. No patients died during the trial.Interpretation: Glepaglutide was well tolerated, and was associated with improved intestinal absorption in patients with short bowel syndrome with 1 mg and 10 mg glepaglutide, but not with 0·1 mg glepaglutide. Larger phase 3 clinical trials of longer durations have been initiated to fully assess the safety and efficacy of glepaglutide.Funding: Zealand Pharma.

AB - Background: Patients with short bowel syndrome might have impaired postprandial endogenous glucagon-like peptide-2 (GLP-2) secretion, which is required for optimal intestinal adaptation. We aimed to assess the therapeutic potential of glepaglutide, a novel long-acting GLP-2 analogue, for reducing faecal output and increasing intestinal absorption in patients with short bowel syndrome.Methods: In this single-centre, double-blind, crossover, randomised phase 2 trial, adults (aged ≥18 to ≤90 years) with short bowel syndrome and with a faecal wet weight output of 1500 g/day or more were randomly assigned to receive one of six dose sequences of glepaglutide (10 mg, 1 mg; 10 mg, 0·1 mg; 1 mg, 10 mg; 1 mg, 0·1 mg; 0·1 mg, 10 mg; or 0·1 mg, 1 mg). Patients received daily subcutaneous injections of the first assigned dose of glepaglutide for 3 weeks, followed by a washout period of 4-8 weeks, and then the second dose of glepaglutide for 3 weeks. An unmasked statistician generated the randomisation list, and the trial investigator enrolled patients and assigned them their patient numbers. Trial investigators, patients, and other care providers were masked throughout the trial. The primary endpoint was the absolute change from baseline in faecal wet weight output, measured separately over the two treatment periods. Metabolic balance studies were done before and after each treatment period to assess the primary endpoint. Per-protocol analysis was used to assess the efficacy. Safety analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02690025, and has completed.Findings: Of the 22 patients screened between Feb 5, 2016, and Jan 25, 2017, 18 patients were randomly assigned and treated with glepaglutide; 16 patients completed the trial. Treatment with 1 mg and 10 mg glepaglutide changed the adjusted mean faecal output by -592 g/day (95% CI -913 to -272; p=0·002) and -833 g/day (-1152 to -515; p=0·0002) from baseline, respectively. No changes were observed with 0·1 mg glepaglutide. Of the 18 patients who were randomly assigned to treatment, common treatment-related adverse events were stoma complications (13 [72%] patients), injection site reactions (11 [61%]), peripheral oedema (ten [56%]), nausea and abdominal pain (eight [44%] each), polyuria and fatigue (six [33%] each), abdominal distention, vomiting, and dizziness (five [28%] each); and cough and decreased appetite (four [22%] each). Related or possibly related serious adverse events were reported in two patients in the 0·1 mg dose group and two patients in the 10 mg dose group. These events included abdominal pain, stoma obstruction, catheter-related sepsis, and infection of unknown origin. No patients died during the trial.Interpretation: Glepaglutide was well tolerated, and was associated with improved intestinal absorption in patients with short bowel syndrome with 1 mg and 10 mg glepaglutide, but not with 0·1 mg glepaglutide. Larger phase 3 clinical trials of longer durations have been initiated to fully assess the safety and efficacy of glepaglutide.Funding: Zealand Pharma.

U2 - 10.1016/S2468-1253(19)30077-9

DO - 10.1016/S2468-1253(19)30077-9

M3 - Journal article

VL - 4

SP - 354

EP - 363

JO - The Lancet Gastroenterology and Hepatology

JF - The Lancet Gastroenterology and Hepatology

SN - 2468-1253

IS - 5

ER -

ID: 215233659