Effect of Methylnaltrexone on GI Transit in Healthy Volunteers

NCT01055704 | Completed Phase 4 Results

• 1 other identifier: 09-002996
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Gastric Motility Disorder

Keywords

Methylnaltrexone; Codeine; Gastrointestinal motility; Colonic transit

Outcome Measures

Primary Outcomes (1)

• Colonic Geometric Center at 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.

  24 hours

Secondary Outcomes (7)

• T1/2 of Ascending Colon Emptying

  24 hours

• T1/2 of Gastric Emptying of Solid

  4 hours

• Colonic Geometric Center at 4 Hours

  4 hours

• Colonic Geometric Center at 48 Hours

  48 hours

• Colonic Filling at 6 Hours

  6 hours

Study Arms (4)

Methylnaltrexone

EXPERIMENTAL

Drug: Methylnaltrexone only

Codeine

EXPERIMENTAL

Drug: Codeine only

Methylnaltrexone + codeine

EXPERIMENTAL

Drug: Methylnaltrexone + codeine

Placebo

PLACEBO COMPARATOR

Drug: Placebo + placebo

Interventions

Methylnaltrexone only DRUG

0.30 mg/kg subcutaneous injection daily

Also known as: MNTX, Relistor

Methylnaltrexone

Codeine only DRUG

30 mg taken orally four times daily for 5 days

Codeine

Methylnaltrexone + codeine DRUG

Methylnaltrexone 0.30 mg/kg by subcutaneous injection once daily and codeine 30 mg taken orally four times daily for 5 days

Methylnaltrexone + codeine

Placebo + placebo DRUG

Placebo subcutaneous injection once daily and placebo taken orally four times daily for 5 days

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (1)

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Wong BS, Rao AS, Camilleri M, Manabe N, McKinzie S, Busciglio I, Burton DD, Ryks M, Zinsmeister AR. The effects of methylnaltrexone alone and in combination with acutely administered codeine on gastrointestinal and colonic transit in health. Aliment Pharmacol Ther. 2010 Oct;32(7):884-93. doi: 10.1111/j.1365-2036.2010.04422.x.

  PMID: 20839388 RESULT

MeSH Terms

Interventions

methylnaltrexone; Codeine

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

We did not evaluate dose-response. A higher dosage of MNTX may be needed to produce a detectable effect on GI and colonic transit as well as bowel pattern in healthy subjects who are naive to opioid agonists during MNTX initiation.

Results Point of Contact

• Title: Dr Michael Camilleri
• Organization: Mayo Clinic

camilleri.michael@mayo.edu

5072662305

Study Officials

• Michael Camilleri, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 22, 2010
• First Posted: January 26, 2010
• Study Start: November 1, 2009
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: June 25, 2012
• Results First Posted: August 8, 2011

Record last verified: 2012-06

Locations

US (1)