Clinical trial NCT01055704
Conditions: Gastric Motility Disorder
Keywords: Methylnaltrexone Codeine Gastrointestinal motility Colonic transit
Sponsor: Mayo Clinic
Start date: 2009-11-01; Completion date: 2010-02-01
Enrollment: 48 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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. 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

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.

Arms: arm 1: None arm 2: None arm 3: None arm 4: None
Interventions: intervention 1: Methylnaltrexone only intervention 2: Codeine only intervention 3: Methylnaltrexone + codeine intervention 4: Placebo + placebo
Intervention descriptions: intervention 1: 0.30 mg/kg subcutaneous injection daily intervention 2: 30 mg taken orally four times daily for 5 days intervention 3: Methylnaltrexone 0.30 mg/kg by subcutaneous injection once daily and codeine 30 mg taken orally four times daily for 5 days intervention 4: Placebo subcutaneous injection once daily and placebo taken orally four times daily for 5 days

Protocol documents: