Trial Outcomes & Findings for Effect of Methylnaltrexone on GI Transit in Healthy Volunteers (NCT NCT01055704)

NCT ID: NCT01055704

Last Updated: 2012-06-25

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 48 participants
• Primary outcome timeframe: 24 hours
• Results posted on: 2012-06-25

Participant Flow

Study participants included males and non-pregnant, non-breastfeeding females aged 18 to 55 years. All subjects had a minimum body mass index (BMI) of 22 kg/m2.

Subjects were screened for eligibility within 28 days of Day 1 of the study. They were stratified based on gender and BMI (<25, ≥25 kg/m2) and randomized into one of four treatment groups: Treatment groups were randomly assigned in fixed block sizes according to a schedule provided by the study statistician (ARZ). Allocation sequence was concealed

Participant milestones

Measure	Methylnaltrexone 0.30 mg/kg	Codeine 30 mg	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg	Placebo
Overall Study STARTED	16	8	16	8
Overall Study COMPLETED	16	8	16	8
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Methylnaltrexone on GI Transit in Healthy Volunteers

Baseline characteristics by cohort

Measure	Methylnaltrexone 0.30 mg/kg n=16 Participants	Codeine 30 mg n=8 Participants	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg n=16 Participants	Placebo n=8 Participants	Total n=48 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants	8 Participants n=4 Participants	48 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age Continuous	33.9 years STANDARD_DEVIATION 2.6 • n=5 Participants	39.4 years STANDARD_DEVIATION 3.8 • n=7 Participants	31.6 years STANDARD_DEVIATION 2.7 • n=5 Participants	36.1 years STANDARD_DEVIATION 3.6 • n=4 Participants	37.5 years STANDARD_DEVIATION 2.4 • n=21 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants	5 Participants n=4 Participants	31 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	3 Participants n=4 Participants	17 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Methylnaltrexone 0.30 mg/kg n=16 Participants	Codeine 30 mg n=8 Participants	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg n=16 Participants	Placebo n=8 Participants
Colonic Geometric Center at 24 Hours	2.3 Units on a scale Standard Error 0.2	1.8 Units on a scale Standard Error 0.2	1.9 Units on a scale Standard Error 0.3	2.3 Units on a scale Standard Error 0.4

SECONDARY outcome

Timeframe: 24 hours

Outcome measures

Measure	Methylnaltrexone 0.30 mg/kg n=16 Participants	Codeine 30 mg n=8 Participants	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg n=16 Participants	Placebo n=8 Participants
T1/2 of Ascending Colon Emptying	17.1 hours Standard Error 2.2	24.0 hours Standard Error 3.9	23.6 hours Standard Error 3.3	14.1 hours Standard Error 2.6

SECONDARY outcome

Timeframe: 4 hours

Outcome measures

Measure	Methylnaltrexone 0.30 mg/kg n=16 Participants	Codeine 30 mg n=8 Participants	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg n=16 Participants	Placebo n=8 Participants
T1/2 of Gastric Emptying of Solid	102.7 Minutes Standard Error 5.1	104.0 Minutes Standard Error 14.1	126.8 Minutes Standard Error 11.9	101.1 Minutes Standard Error 6.2

SECONDARY outcome

Timeframe: 4 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.

Outcome measures

Measure	Methylnaltrexone 0.30 mg/kg n=16 Participants	Codeine 30 mg n=8 Participants	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg n=16 Participants	Placebo n=8 Participants
Colonic Geometric Center at 4 Hours	0.236 Units on a scale Standard Error 0.105	0 Units on a scale Standard Error 0	0.379 Units on a scale Standard Error 0.130	0.347 Units on a scale Standard Error 0.229

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Methylnaltrexone 0.30 mg/kg n=16 Participants	Codeine 30 mg n=8 Participants	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg n=16 Participants	Placebo n=8 Participants
Colonic Geometric Center at 48 Hours	3.9 Units on a scale Standard Error 0.3	3.3 Units on a scale Standard Error 0.4	2.8 Units on a scale Standard Error 0.3	4.1 Units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: 6 hours

Percent of solids reaching the colon at 6 hours

Outcome measures

Measure	Methylnaltrexone 0.30 mg/kg n=16 Participants	Codeine 30 mg n=8 Participants	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg n=16 Participants	Placebo n=8 Participants
Colonic Filling at 6 Hours	21.9 Percentage Standard Error 5.7	23.7 Percentage Standard Error 11.2	28.0 Percentage Standard Error 6.9	34.5 Percentage Standard Error 14.1

SECONDARY outcome

Timeframe: daily

Stool frequency was self reported in a daily bowel pattern diary for 13 days.

Outcome measures

Measure	Methylnaltrexone 0.30 mg/kg n=16 Participants	Codeine 30 mg n=8 Participants	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg n=16 Participants	Placebo n=8 Participants
Stool Frequency	1.1 Stools Standard Error 0.1	0.63 Stools Standard Error 0.2	0.7 Stools Standard Error 0.1	1.5 Stools Standard Error 0.4

SECONDARY outcome

Timeframe: Daily

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.

Outcome measures

Measure	Methylnaltrexone 0.30 mg/kg n=16 Participants	Codeine 30 mg n=8 Participants	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg n=16 Participants	Placebo n=8 Participants
Stool Consistency as Reported From the Bristol Stool Scale	3.4 Units on a scale Standard Error 0.3	3.1 Units on a scale Standard Error 0.5	3.3 Units on a scale Standard Error 0.3	3.7 Units on a scale Standard Error 0.3

Adverse Events

Methylnaltrexone 0.30 mg/kg

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Codeine 30 mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Methylnaltrexone 0.30 mg/kg + Codeine 30 mg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Methylnaltrexone 0.30 mg/kg n=16 participants at risk	Codeine 30 mg n=8 participants at risk	Methylnaltrexone 0.30 mg/kg + Codeine 30 mg n=16 participants at risk	Placebo n=8 participants at risk
Skin and subcutaneous tissue disorders Burn or sting with injection	43.8% 7/16 • Number of events 7 • 10 days	25.0% 2/8 • Number of events 2 • 10 days	12.5% 2/16 • Number of events 2 • 10 days	62.5% 5/8 • Number of events 5 • 10 days
Nervous system disorders Fatigue	18.8% 3/16 • Number of events 3 • 10 days	37.5% 3/8 • Number of events 3 • 10 days	31.2% 5/16 • Number of events 5 • 10 days	0.00% 0/8 • 10 days
Gastrointestinal disorders Flatulence	31.2% 5/16 • Number of events 5 • 10 days	25.0% 2/8 • Number of events 2 • 10 days	6.2% 1/16 • Number of events 1 • 10 days	25.0% 2/8 • Number of events 2 • 10 days
General disorders Headache	18.8% 3/16 • Number of events 3 • 10 days	37.5% 3/8 • Number of events 3 • 10 days	12.5% 2/16 • Number of events 2 • 10 days	0.00% 0/8 • 10 days
Nervous system disorders Sleepiness	6.2% 1/16 • Number of events 1 • 10 days	25.0% 2/8 • Number of events 2 • 10 days	31.2% 5/16 • Number of events 5 • 10 days	0.00% 0/8 • 10 days
Gastrointestinal disorders Constipation	12.5% 2/16 • Number of events 2 • 10 days	25.0% 2/8 • Number of events 2 • 10 days	12.5% 2/16 • Number of events 2 • 10 days	0.00% 0/8 • 10 days
Gastrointestinal disorders Nausea	0.00% 0/16 • 10 days	37.5% 3/8 • Number of events 3 • 10 days	12.5% 2/16 • Number of events 2 • 10 days	0.00% 0/8 • 10 days
Gastrointestinal disorders Emesis	0.00% 0/16 • 10 days	12.5% 1/8 • Number of events 1 • 10 days	18.8% 3/16 • Number of events 3 • 10 days	12.5% 1/8 • Number of events 1 • 10 days
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.2% 1/16 • Number of events 1 • 10 days	0.00% 0/8 • 10 days	18.8% 3/16 • Number of events 3 • 10 days	12.5% 1/8 • Number of events 1 • 10 days
Gastrointestinal disorders Abdominal bloating	18.8% 3/16 • Number of events 3 • 10 days	0.00% 0/8 • 10 days	0.00% 0/16 • 10 days	0.00% 0/8 • 10 days

Additional Information

Dr Michael Camilleri

Mayo Clinic

Phone: 5072662305

Email: camilleri.michael@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place