Effect of Methylnaltrexone on GI Transit in Healthy Volunteers

This study has been completed.
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01055704
First received: January 22, 2010
Last updated: June 20, 2012
Last verified: June 2012
  Purpose

This is a single-center, randomized, double blind, placebo-controlled study evaluating the effects of placebo, codeine, methylnaltrexone and codeine with methylnaltrexone on gastrointestinal motility and colonic transit of solids in healthy human subjects.

The hypotheses are:

  1. Methylnaltrexone administered subcutaneously enhances gastrointestinal motility with acceleration of overall colonic transit, and ascending colon emptying of solids in healthy humans.
  2. Methylnaltrexone significantly accelerates colonic transit that is delayed by codeine

Condition Intervention Phase
Gastric Motility Disorder
Drug: Methylnaltrexone only
Drug: Codeine only
Drug: Methylnaltrexone + codeine
Drug: Placebo + placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Methylnaltrexone on Gastrointestinal and Colonic Transit in Health

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Colonic Geometric Center at 24 Hours [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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:
  • T1/2 of Ascending Colon Emptying [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • T1/2 of Gastric Emptying of Solid [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
  • Colonic Geometric Center at 4 Hours [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
    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.

  • Colonic Geometric Center at 48 Hours [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    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.

  • Colonic Filling at 6 Hours [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
    Percent of solids reaching the colon at 6 hours

  • Stool Frequency [ Time Frame: daily ] [ Designated as safety issue: No ]
    Stool frequency was self reported in a daily bowel pattern diary for 13 days.

  • Stool Consistency as Reported From the Bristol Stool Scale [ Time Frame: Daily ] [ Designated as safety issue: No ]
    Bristol Stool Scale a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation, with 3 and 4 being the "ideal stools" especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea.


Enrollment: 48
Study Start Date: November 2009
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methylnaltrexone Drug: Methylnaltrexone only
0.30 mg/kg subcutaneous injection daily
Other Names:
  • MNTX
  • Relistor
Experimental: Codeine Drug: Codeine only
30 mg taken orally four times daily for 5 days
Experimental: Methylnaltrexone + codeine Drug: Methylnaltrexone + codeine
Methylnaltrexone 0.30 mg/kg by subcutaneous injection once daily and codeine 30 mg taken orally four times daily for 5 days
Placebo Comparator: Placebo Drug: Placebo + placebo
Placebo subcutaneous injection once daily and placebo taken orally four times daily for 5 days

Detailed Description:

Methodology

Following the initial screening visit (visit 1), participants will be randomized to study medication, either 0.30mg/kg methylnaltrexone subcutaneously or placebo once daily and 30 mg codeine orally or placebo taken four times daily for a total of five days. Participants will be randomly assigned to study medication and allocation will be concealed. A urine pregnancy test will be performed for all females of child bearing potential within the 48 hours prior to the receipt of study medication. Note that females who are status post bilateral tubal ligation, hysterectomy or postmenopausal are exempted from this test. Study medication will be administered on study med days 1, 2 and 3 (visits 2, 3 and 4) at the Clinical Research Unit (CRU). Participants will return for scintigraphic assessment of gastric, small bowel and colonic transit of solids on study med days 4 and 5 (visits 5 and 6). The transit studies will be undertaken on over a 48 hour time period; no study medication is given on the final day of transit (visit 7).

Investigational product, dosage, mode of administration, duration of treatment

0.30 mg/kg methylnaltrexone or placebo subcutaneously once daily and 30 mg codeine or placebo orally four times daily for five consecutive days.

Treatment groups

  1. placebo + placebo (8 participants)
  2. placebo + codeine 120mg (8 participants)
  3. methylnaltrexone 0.30 mg/kg + placebo (16 participants)
  4. methylnaltrexone 0.30 mg/kg + codeine 120 mg (16 participants)

Efficacy assessments

  1. Scintigraphic gastrointestinal and colonic transit
  2. Assessment of bowel pattern frequency and consistency made by the patient using the bowel pattern diary

Safety assessments

No safety assessments (routine laboratory analysis, ECG etc) will be performed as both methylnaltrexone and codeine are FDA approved medications

Statistical analysis

The overall effects of the methylnaltrexone treatment on the primary and secondary response measures will be assessed using an analysis of covariance (ANCOVA) with suitable transformation for skewness in the distributions of measured responses if necessary (e.g., ANCOVA on ranks or an arcsine square root transformation for the proportion of marker in the colon at 6 hours). The covariates considered for inclusion in the analyses will be age, gender and body mass index. An a priori anticipated contrast (overall drug vs. placebo) will be examined (α = 0.05). The specific comparisons of methylnaltrexone vs placebo and codeine vs codeine plus methylnaltrexone are of significant interest, and since they are related to specific hypotheses, no change in α from 0.05 is planned.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • Males and non-pregnant, non-breastfeeding females
  • 18-65 years old
  • No functional GI disorders on the short Bowel Disease Questionnaire (BDQ)
  • A BMI greater than 22.0

Exclusion criteria

  • Structural or metabolic diseases/conditions that affect the gastrointestinal system or functional gastrointestinal disorders. The short version of the Bowel Disease Questionnaire (BDQ) will be exclude functional GI disorders. More than three positive responses will exclude participation.
  • Unable to withdraw from the following medications 48 hours prior to study entry:Any medication that alters GI transit including but not limited to laxatives, magnesium or aluminum-containing antacids, prokinetics, erythromycin, narcotics, anticholinergics, tricyclic antidepressants, SSRI and newer antidepressants; analgesic drugs including opiates, NSAID, COX 2 inhibitors (note : Tylenol is permitted); GABAergic agents and benzodiazepines. Note: Concomitant medications will be reviewed on a case by case basis by the study physicians.
  • Subjects who are considered by the investigator to be alcoholics not in remission or known substance abusers. Alcohol must be avoided from seven days prior to beginning the study medication until the completion of the study.
  • Subjects who have participated in another clinical study within the past 30 days.
  • Clinical evidence (including physical exam and review of the medical history) of significant cardiovascular, respiratory, renal, hepatic, pulmonary, gastrointestinal, hematological, neurological, psychiatric, or other disease that interfere with the objectives of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01055704

Locations
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Principal Investigator: Michael Camilleri, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Michael Camilleri, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01055704     History of Changes
Other Study ID Numbers: 09-002996
Study First Received: January 22, 2010
Results First Received: July 8, 2011
Last Updated: June 20, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Methylnaltrexone
Codeine
Gastrointestinal motility
Colonic transit

Additional relevant MeSH terms:
Codeine
Methylnaltrexone
Naltrexone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Antitussive Agents
Respiratory System Agents
Narcotic Antagonists

ClinicalTrials.gov processed this record on August 28, 2014