Clinical trial : Randomized controlled trial of linaclotide in children aged 6-17 years with functional constipation
© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition..
OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for treatment of children 6-17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6-17 years old with FC.
METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 2 study, 173 children with FC (based on Rome III criteria) were randomized to once-daily linaclotide (A: 9 or 18 μg, B: 18 or 36 μg, or C: 36 or 72 μg) or placebo in a 1:1:1:1 ratio for 6- to 11-year-olds (dosage determined by weight: 18 to <35 or ≥35 kg) and linaclotide (18, 36, 72, or 145 μg) or placebo in a 1:1:1:1:1 ratio for 12- to 17-year-olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4-week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored.
RESULTS: Efficacy and safety were assessed in 173 patients (52.0% aged 6-11 years; 48.0% aged 12-17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBM frequency was observed with increasing linaclotide doses (1.90 in 6- to 11-year-olds [36 or 72 μg] and 2.86 in 12- to 17-year-olds [72 μg]). The most reported treatment-emergent AE was diarrhea, with most cases being mild; none were severe.
CONCLUSIONS: Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Journal of pediatric gastroenterology and nutrition - (2024) vom: 27. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Di Lorenzo, Carlo [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Constipation |
|---|
| Anmerkungen: |
Date Revised 27.03.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1002/jpn3.12184 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370231848 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370231848 | ||
| 003 | DE-627 | ||
| 005 | 20240328001023.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240328s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/jpn3.12184 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1351.xml |
| 035 | |a (DE-627)NLM370231848 | ||
| 035 | |a (NLM)38533633 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Di Lorenzo, Carlo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical trial |b Randomized controlled trial of linaclotide in children aged 6-17 years with functional constipation |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 27.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. | ||
| 520 | |a OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for treatment of children 6-17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6-17 years old with FC | ||
| 520 | |a METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 2 study, 173 children with FC (based on Rome III criteria) were randomized to once-daily linaclotide (A: 9 or 18 μg, B: 18 or 36 μg, or C: 36 or 72 μg) or placebo in a 1:1:1:1 ratio for 6- to 11-year-olds (dosage determined by weight: 18 to <35 or ≥35 kg) and linaclotide (18, 36, 72, or 145 μg) or placebo in a 1:1:1:1:1 ratio for 12- to 17-year-olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4-week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored | ||
| 520 | |a RESULTS: Efficacy and safety were assessed in 173 patients (52.0% aged 6-11 years; 48.0% aged 12-17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBM frequency was observed with increasing linaclotide doses (1.90 in 6- to 11-year-olds [36 or 72 μg] and 2.86 in 12- to 17-year-olds [72 μg]). The most reported treatment-emergent AE was diarrhea, with most cases being mild; none were severe | ||
| 520 | |a CONCLUSIONS: Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a constipation | |
| 650 | 4 | |a functional GI diseases | |
| 650 | 4 | |a pediatric gastroenterology | |
| 650 | 4 | |a small intestine | |
| 700 | 1 | |a Nurko, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Hyams, Jeffrey S |e verfasserin |4 aut | |
| 700 | 1 | |a Rodriguez-Araujo, Gerardo |e verfasserin |4 aut | |
| 700 | 1 | |a Almansa, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Shakhnovich, Valentina |e verfasserin |4 aut | |
| 700 | 1 | |a Saps, Miguel |e verfasserin |4 aut | |
| 700 | 1 | |a Simon, Michael |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of pediatric gastroenterology and nutrition |d 1982 |g (2024) vom: 27. März |w (DE-627)NLM012621927 |x 1536-4801 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:27 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/jpn3.12184 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 27 |c 03 | ||