- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02737059
Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects
A Phase I Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
- Body Mass Index (BMI) between 19 and 30 kg/m^2 and absolute weight between 45 and 100 kg. for both males and females.
- Females who are non-pregnant, non-lactating, postmenopausal for at least one year (as evidenced by last menses 12 months from Day 0), surgically sterile, or willing to use a clinically-approved method of contraception from 35 days prior to Day 0 until 30 days after the last dose of study medication
- Males who are surgically sterile or willing to use a clinically approved method of contraception from Day 0 until 30 days after the last dose of study medication.
- Absence of gastrointestinal symptoms unless deemed not clinically significant by the Investigator.
- Able to understand and willing to sign informed consent
- Negative urine drug screen at screening
Exclusion criteria:
- Structural or metabolic diseases/conditions that affect the gastrointestinal system, or functional gastrointestinal disorders. For screening, three or more "YES" responses on the Bowel Disease Questionnaire will be used to exclude subjects with irritable bowel syndrome.
- Use of drugs or agents within the past 2 weeks or planned use in the subsequent 4 weeks during the study period that: Alter GI transit including laxatives, magnesium or aluminum-containing antacids, prokinetic, erythromycin, narcotics, anticholinergics, tricyclic antidepressants, Selective serotonin re-uptake inhibitors (SSRI) and newer antidepressants.
- Analgesic drugs including opiates, NSAID, cyclooxygenase-2 (COX 2) inhibitors
- Use of non-prescription or prescription medications within 7 days or within five half-lives prior to Day 0 for that particular medication. Note: Low stable doses of thyroid replacement, estrogen replacement, and birth control pills or depot injections, and use of acetaminophen on as needed basis are permissible.
- A score of greater than or equal to 11 for either score obtained from the Hospital Anxiety Depression Scale
- Positive urine drug screen at screening
- Female subjects who are pregnant or breast feeding.
- Clinical evidence (including physical exam, previous laboratory tests) or significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric, or other disease that interfere with the objectives of the study. Patients with previously high transaminase levels (AST, ALT) may be retested and if the results are less than 1.5 times the upper limit of normal will be included as long as they do not have an underlying known liver disease.
- Symptoms of a significant clinical illness in the preceding two weeks.
- Participation in another clinical study within the past 30 days.
- Subjects known allergy or hypersensitive to multiple drug compounds (greater than or equal to 3 drug compounds), naloxegol or opioid antagonists, codeine sulfate, eggs or any components of the study medication
- Daily use of any tobacco products within 6 months prior to Day 0
- Previous exposure to naloxegol
- Any other conditions or prior therapy which, in the opinion of the Investigator, would make the subject unsuitable for this study
- Contraindications to use of naloxegol in accordance with FDA guidance: suspected GI obstruction or at increased risk of recurrent obstruction; concomitant use of strong CYP3A4 inhibitors such as clarithromycin and ketoconazole
- Concomitant treatment with moderate CYP3A4 inhibitors (diltiazem, erythromycin, verapamil) or strong CYP3A4 inducers (rifampin) or other opioid antagonists.
- History of substance abuse.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Codeine/naloxegol placebo
Each 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. |
30mg 4 times daily
placebo will match naloxegol, given daily
|
Placebo Comparator: Naloxegol/ codeine placebo
Each 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. |
25mg daily
Other Names:
4 times daily (placebo will be made to match the codeine)
|
Active Comparator: Codeine/ naloxegol
Each 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. |
30mg 4 times daily
25mg daily
Other Names:
|
Active Comparator: codeine placebo/ naloxegol placebo
Each 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. |
placebo will match naloxegol, given daily
4 times daily (placebo will be made to match the codeine)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Gastric emptying (t1/2)
Time Frame: Day 2
|
The time for half of the ingested solids or liquids to leave the stomach.
|
Day 2
|
Colonic filling (%) at 6 hours
Time Frame: Day 2 (6 hours)
|
Percent of the radio-labeled meal that reached the colon at 6 hours, indirectly reflecting small bowel transit time.
|
Day 2 (6 hours)
|
Colonic geometric center (GC) at 24 hours
Time Frame: Day 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.
|
Day 2 ( 24 hours)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 hours
Time Frame: Day 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.
|
Day 2 (48 hours)
|
Ascending Colon Emptying (ACE) T1/2
Time Frame: Day 2
|
Ascending colon emptying half-time will be estimated by power exponential analysis of the proportionate emptying over time of counts from the colon.
|
Day 2
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 15-007863
- UL1TR000135 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Constipation Drug Induced
-
AstraZenecaCompletedDrug Induced ConstipationUnited States
-
AstraZenecaCompletedDrug Induced ConstipationUnited States
-
TriHealth Inc.Recruiting
-
AstraZenecaCompletedDrug Induced ConstipationUnited States
-
University of Missouri-ColumbiaCompletedConstipation Drug InducedUnited States
-
University of ChileCompletedCritical Illness | Constipation | Constipation Drug InducedChile
-
Fondazione ANT Italia ONLUSCompletedCancer | Opioid Use | Constipation Drug InducedItaly
-
Istanbul Aydın UniversityIstanbul University; Acibadem UniversityRecruitingOpioid-induced Bowel Dysfunction | Constipation Drug InducedTurkey
-
Alexandria UniversityCompletedDrug Side Effect | Treatment Efficacy | Clinical EfficacyEgypt
-
Amsterdam UMC, location VUmcRadboud University Medical Center; University Medical Center Groningen; UMC Utrecht and other collaboratorsRecruitingConstipation, Opioid-InducedNetherlands
Clinical Trials on Codeine
-
University of ZimbabweUZ-CHS-PERFECTSuspendedImpacted Third Molar Tooth | PAINZimbabwe
-
Children's Hospitals and Clinics of MinnesotaCompletedPain | TonsillitisUnited States
-
University of Southern DenmarkCompletedMetformin | Organic Cation Transporter 1 | CodeineDenmark
-
Mayo ClinicWyeth is now a wholly owned subsidiary of PfizerCompletedGastric Motility DisorderUnited States
-
Roxane LaboratoriesCompleted
-
Roxane LaboratoriesCompleted
-
Aziende Chimiche Riunite Angelini Francesco S.p.ACross Research S.A.Completed
-
Universitaire Ziekenhuizen KU LeuvenCompleted