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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02737059
Recruitment Status : Completed
First Posted : April 13, 2016
Last Update Posted : August 30, 2017
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Michael Camilleri, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE April 8, 2016
First Posted Date  ICMJE April 13, 2016
Last Update Posted Date August 30, 2017
Actual Study Start Date  ICMJE July 1, 2016
Actual Primary Completion Date May 10, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2017)
  • Gastric emptying (t1/2) [ Time Frame: Day 2 ]
    The time for half of the ingested solids or liquids to leave the stomach.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 8, 2016)
  • Gastric emptying (t1/2) [ Time Frame: Day 2 ]
  • Colonic filling (%) at 6 hours [ Time Frame: Day 2 (6 hours) ]
  • Colonic geometric center (GC) at 24 hours [ Time Frame: Day 2 ( 24 hours) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2017)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2016)
  • Colonic transit summarized by GC at 4 and 48 hours hours colonic transit summarized by GC at 4 and 48 hours Colonic transit at 4 and 48 hours [ Time Frame: day 2, day 3 ]
  • Percent of standardized meal remaining in the stomach at 2 and 4 hours [ Time Frame: Day 2 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects
Official Title  ICMJE A Phase I Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Constipation Drug Induced
Intervention  ICMJE
  • Drug: Naloxegol
    25mg daily
    Other Name: MOVANTIK
  • Drug: Codeine
    30mg 4 times daily
  • Drug: codeine placebo
    4 times daily (placebo will be made to match the codeine)
  • Drug: naloxegol placebo
    placebo will match naloxegol, given daily
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: Codeine
    • Drug: naloxegol placebo
  • 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.

    Interventions:
    • Drug: Naloxegol
    • Drug: codeine placebo
  • 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.

    Interventions:
    • Drug: Naloxegol
    • Drug: Codeine
  • 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.

    Interventions:
    • Drug: codeine placebo
    • Drug: naloxegol placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 8, 2016)
72
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 10, 2017
Actual Primary Completion Date May 10, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02737059
Other Study ID Numbers  ICMJE 15-007863
UL1TR000135 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Michael Camilleri, Mayo Clinic
Study Sponsor  ICMJE Michael Camilleri
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Michael Camilleri, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP