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Study of Methylnaltrexone in Opioid-Induced Constipation Patients

Phase 2
Conditions
Opioid-induced Constipation
Interventions
Registration Number
NCT02574819
Lead Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Brief Summary

This is a multicenter, randomized, double-blind , placebo-controlled trail to investigate the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness.

Detailed Description

Methylnaltrexone is a quaternary derivative of the pure opioid antagonists naltrexone. It is fairly lipid soluble and readily cross the blood-brain barrier. This property provides methylnaltrexone with the potential to block the undesired side-effects of opioid pain medications predominantly mediated by receptors located peripherally while sparing opioid effects mediated at receptors in the central nervous system, most importantly analgesia.

This is a multicenter, randomized, double-blind , placebo-controlled trail to investigate the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness. The randomization schedule was used to assign patients in a 2:1 ratio to multicenter or an equal volume of placebo administered subcutaneously on alternate days for 2 weeks. The clinical trail was estimated to enroll 180 patients totally.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
198
Inclusion Criteria
  • A life expectancy of 3 month or more
  • Qualifying patients received opioids for analgesia for 1 week or more and a stable regimen of opioids and laxatives for 3 or more days before study entry
  • Patients had opioid-induced constipation with either fewer than three laxation during the preceding week and no clinically meaningful laxation (as determined by the in investigator ) within 24h before the first study dose or no clinically meaningful laxation within 48h before the first study dose
  • During the two-week trail , patients would keep their life habits (dietary fiber , fluid intake and physical activity)
  • Patients volunteered for the trail
  • Women of childbearing potential had negative pregnancy tests. Both male and female patients need to take effective contraceptives to avoid pregnancy.
Exclusion Criteria
  • Constipation that was not primarily caused by opioids ( as determined by the investigator)
  • Mechanical gastrointestinal obstruction, an indwelling peritoneal catheter, clinically active diverticular disease , fecal impaction , acute surgical abdomen , and fecal ostomy
  • Patients had the surgery plan which would effect the results of pain assessment
  • Patients had hypersensitivity to methylnaltrexone , naltrexone or naloxone or if any investigational drug or experimental product

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo administered every other day for 2 weeks.
DrugMethylnaltrexone (MNTX)Methylnaltrexone (MNTX) nearly 0.15mg/kg administered every other day for 2 weeks.
Primary Outcome Measures
NameTimeMethod
The proportion of subjects who had the Rescue-free laxation response within 4 hours of the initial doseup to 4 hours

Within 4 hours after the initial dose, if clinical significant bowel movement happened, the drug therapeutic effect was confirm. In the meantime, the time of bowel movement and other properties of bowel movement were recorded. The percentage of patients who had rescue-free laxation response is the primary outcome.

Secondary Outcome Measures
NameTimeMethod
The proportion of subjects who had Rescue-free laxation response within 4 hours after each doses from the second dose to the last doseup to 12 days
The proportion of subjects who had at least 2 Rescue-free laxation responses within 4 hours after each doses from the first dose to the forth doseup to 8 days

Record the frequency of laxation. After 1-4 dose, within 4 hours of every dose, record the dose number when bowel movement happened

The proportion of subjects who had Rescue-free laxation response within 4-24h after each doseup to 14 days
The proportion of subjects who had ≥3 laxation responses per weekup to 2 weeks

Trial Locations

Locations (12)

Henan Provincial Cancer Hospital

🇨🇳

Zhengzhou, Henan, China

The Affiliated Hospital of Xuzhou Medical College

🇨🇳

Xuzhou, Jiangsu, China

Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine Chongming Branch

🇨🇳

Shanghai, Shanghai, China

Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

🇨🇳

Shanghai, Shanghai, China

Tangdu Hospital

🇨🇳

Xian, Shanxi, China

Jiangxi Cancer Hospital

🇨🇳

Nanchang, Jiangxi, China

The Second Hospital of Anhui Medical University

🇨🇳

Hefei, Anhui, China

Harbin Medical University Cancer Hospital

🇨🇳

Harbin, Heilongjiang, China

Fujian Provincial cancer Hospital

🇨🇳

Fuzhou, Fujian, China

Zhongnan Hospital of Wuhan University

🇨🇳

Wuhan, Hebei, China

Linyi Cancer Hospital

🇨🇳

Linyi, Shandong, China

Tumor Hospital of Yunnan Province The Third Affiliated Hospital of Kunming Medical University

🇨🇳

Kunming, Yunnan, China

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