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Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects

Phase 1
Completed
Conditions
Constipation Drug Induced
Interventions
Registration Number
NCT02737059
Lead Sponsor
Michael Camilleri
Brief Summary

This research study was being done to study the effect of codeine and Naloxegol for 3 days compared to placebo on the movement of food through the colon of healthy individuals. Codeine is a commonly used pain-relieving drug that often causes constipation as an unwanted side effect. Naloxegol is a medication recently approved by the FDA for treatment of constipation induced by Codeine.

The hypothesis for this study was that Naloxegol reduces the retardation of small bowel and colonic transit induced by codeine in healthy participants.

Detailed Description

This was a single center, randomized, double-blind, placebo-controlled, parallel-group, Phase I study of the effects of naloxegol, a novel mu-opioid antagonist, on gastrointestinal and colonic transit in the presence or absence of the mu-opiate, codeine. There is a need to develop effective medications for the treatment of opiate-induced constipation and other motility disorders. Currently available opiates are complicated by addictive potential and induction of troublesome constipation.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
72
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Codeine/naloxegol placebonaloxegol placeboEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Codeine tablet 30 mg q.i.d., and placebo tablet matching naloxegol q.d.
Naloxegol/ codeine placebocodeine placeboEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Naloxegol tablet 25 mg q.d and placebo tablet matching codeine q.i.d.
codeine placebo/ naloxegol placebocodeine placeboEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Placebo tablet matching codeine q.i.d., and placebo tablet matching naloxegol q.d.
codeine placebo/ naloxegol placebonaloxegol placeboEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Placebo tablet matching codeine q.i.d., and placebo tablet matching naloxegol q.d.
Codeine/ naloxegolCodeineEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Codeine tablet 30 mg q.i.d., and naloxegol tablet 25 mg q.d.
Naloxegol/ codeine placeboNaloxegolEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Naloxegol tablet 25 mg q.d and placebo tablet matching codeine q.i.d.
Codeine/ naloxegolNaloxegolEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Codeine tablet 30 mg q.i.d., and naloxegol tablet 25 mg q.d.
Codeine/naloxegol placeboCodeineEach subject will receive two medications to which they are randomized for 1 day before and for the 2 days during transit measurement. Codeine tablet 30 mg q.i.d., and placebo tablet matching naloxegol q.d.
Primary Outcome Measures
NameTimeMethod
Gastric emptying (t1/2)Day 2

The time for half of the ingested solids or liquids to leave the stomach.

Colonic filling (%) at 6 hoursDay 2 (6 hours)

Percent of the radio-labeled meal that reached the colon at 6 hours, indirectly reflecting small bowel transit time.

Colonic geometric center (GC) at 24 hoursDay 2 ( 24 hours)

The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

Secondary Outcome Measures
NameTimeMethod
Colonic transit summarized by GC at 48 hours hours hours colonic transit summarized by GC at 4 and 48 hours Colonic transit at 4 and 48 hoursDay 2 (48 hours)

The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

Ascending Colon Emptying (ACE) T1/2Day 2

Ascending colon emptying half-time will be estimated by power exponential analysis of the proportionate emptying over time of counts from the colon.

Trial Locations

Locations (1)

Mayo Clinic in Rochester

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Rochester, Minnesota, United States

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