Lynn Webster1, Raj Tummala2, Ulysses Diva3, Jaakko Lappalainen4. 1. Vice President of Scientific Affairs, PRA Health Sciences, Salt Lake City, Utah. 2. Director of Clinical Research, AstraZeneca Pharmaceuticals LP, Gaithersburg, Maryland. 3. Principal Statistician, AstraZeneca Pharmaceuticals LP, Gaithersburg, Maryland; now with Ardea Biosciences, San Diego, California. 4. Senior Director of Clinical Research, AstraZeneca Pharmaceuticals LP, Wilmington, Delaware; now with Marinus Pharmaceuticals, Radnor, Pennsylvania.
Abstract
OBJECTIVE: To compare the long-term safety and tolerability of naloxegol with placebo in patients with opioid-induced constipation (OIC) and noncancer pain. DESIGN: Twelve-week, multicenter, randomized, double-blind, parallel-group phase 3 extension study (KODIAC-07, NCT01395524). SETTING: Clinical investigation centers in the United States. PATIENTS: Adult outpatients (N = 302) with confirmed OIC who had completed a 12-week pivotal phase 3 study (KODIAC-04, NCT01309841). INTERVENTIONS: Daily oral administration of naloxegol (12.5 and 25 mg) or placebo. MAIN OUTCOME MEASURES: Adverse events (AEs), including treatment-related AEs, serious AEs, and AEs of special interest; changes from baseline to week 12 in pain scores, daily opioid dose, and symptoms and quality-of-life measurements. RESULTS: No important new AEs occurred during this extension study compared with KODIAC-04. AEs occurred more frequently with naloxegol 25 mg (41.2 percent) versus naloxegol 12.5 mg (34.0 percent) and placebo (33.0 percent). Treatment-emergent AEs occurring in >5 percent of patients in either naloxegol group during the treatment period were arthralgia (25 mg; 5.2 percent) and diarrhea (12.5 mg; 5.3 percent); two reported AEs attributable to opioid withdrawal syndrome in naloxegol groups were deemed unrelated to study medication. None of the gastrointestinal serious AEs was adjudicated as bowel perforation; one patient (naloxegol 12.5 mg) had an event adjudicated as a major cardiovascular event and was unrelated to study medication. Pain scores and daily opioid dose were unchanged, and improvements in symptoms and quality-of-life observed in KODIAC-04 were maintained throughout the extension study. CONCLUSION:Naloxegol was generally safe and well tolerated in this 12-week extension study in patients with noncancer pain and OIC.
RCT Entities:
OBJECTIVE: To compare the long-term safety and tolerability of naloxegol with placebo in patients with opioid-induced constipation (OIC) and noncancer pain. DESIGN: Twelve-week, multicenter, randomized, double-blind, parallel-group phase 3 extension study (KODIAC-07, NCT01395524). SETTING: Clinical investigation centers in the United States. PATIENTS: Adult outpatients (N = 302) with confirmed OIC who had completed a 12-week pivotal phase 3 study (KODIAC-04, NCT01309841). INTERVENTIONS: Daily oral administration of naloxegol (12.5 and 25 mg) or placebo. MAIN OUTCOME MEASURES: Adverse events (AEs), including treatment-related AEs, serious AEs, and AEs of special interest; changes from baseline to week 12 in pain scores, daily opioid dose, and symptoms and quality-of-life measurements. RESULTS: No important new AEs occurred during this extension study compared with KODIAC-04. AEs occurred more frequently with naloxegol 25 mg (41.2 percent) versus naloxegol 12.5 mg (34.0 percent) and placebo (33.0 percent). Treatment-emergent AEs occurring in >5 percent of patients in either naloxegol group during the treatment period were arthralgia (25 mg; 5.2 percent) and diarrhea (12.5 mg; 5.3 percent); two reported AEs attributable to opioid withdrawal syndrome in naloxegol groups were deemed unrelated to study medication. None of the gastrointestinal serious AEs was adjudicated as bowel perforation; one patient (naloxegol 12.5 mg) had an event adjudicated as a major cardiovascular event and was unrelated to study medication. Pain scores and daily opioid dose were unchanged, and improvements in symptoms and quality-of-life observed in KODIAC-04 were maintained throughout the extension study. CONCLUSION:Naloxegol was generally safe and well tolerated in this 12-week extension study in patients with noncancer pain and OIC.
Authors: H Halawi; P Vijayvargiya; I Busciglio; I Oduyebo; D Khemani; M Ryks; D Rhoten; D Burton; L A Szarka; A Acosta; M Camilleri Journal: Neurogastroenterol Motil Date: 2018-02-06 Impact factor: 3.598
Authors: Ana Fernández-Montes; Guillermo de Velasco; Santiago Aguín; Cristina Farriols; María Guirado-Risueño; Vanessa G Jerviz-Guía; María Victoria Baeza-Nadal; Rodolfo Chicas-Sett; José Luis Fírvida; Francisco García-Navalón; Patricia Martín; Carmen Perezagua-Marín; Dulce Rodríguez; Joan Santamaría; Tamara Saurí; Manuel Cobo Journal: Curr Treat Options Oncol Date: 2021-02-26