NCT01596764

Brief Summary

The purpose of this study is to describe the effects of repeated-dose methylnaltrexone in preventing loperamide-induced delay of whole-gut, oro-cecal and colon transit time and to measure pharmacokinetics of methylnaltrexone and naloxone-3-glucuronide after oral administration of methylnaltrexone and naloxone.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 2011

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2011

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2011

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2012

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

May 7, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 11, 2012

Completed
Last Updated

May 11, 2012

Status Verified

May 1, 2012

Enrollment Period

2 months

First QC Date

May 7, 2012

Last Update Submit

May 9, 2012

Conditions

Intestinal Obstruction

Keywords

whole-gut transit timeoro-cecal transit timecolon transit timeloperamide-induced obstipationpharmacokineticsMethylnaltrexoneNaloxone

Outcome Measures

Primary Outcomes (7)

  • Whole-gut transit time (WGT)

    Whole-gut transit time (WGT) was assessed by counting the radio-opaque markers with different shapes (Colon Transit) at different time pints in the feces.

    up to 7 days after administration of the study medication

  • renal clearance (CLR)

    Blood sampling at 48, 49, 50, 50.5, 51, 51.5, 52, 52.5, 53, 53.5, 54, 54.5, 55, 55.5, 56, 57, 58, 60, 62, 64 h and urine sampling 48-60 h after administration of study medication

  • area under the curve of administration window (AUC0-12h)

    48, 49, 50, 50.5, 51, 51.5, 52, 52.5, 53, 53.5, 54, 54.5, 55, 55.5, 56, 57, 58, 60, 62, 64 h after administration of study medication

  • maximum concentration at steady state (Css max)

    48, 49, 50, 50.5, 51, 51.5, 52, 52.5, 53, 53.5, 54, 54.5, 55, 55.5, 56, 57, 58, 60, 62, 64 h after administration of study medication

  • minimum concentration at steady state (Css min)

    48, 49, 50, 50.5, 51, 51.5, 52, 52.5, 53, 53.5, 54, 54.5, 55, 55.5, 56, 57, 58, 60, 62, 64 h after administration of study medication

  • average concentration of administration interval (Cav)

    48, 49, 50, 50.5, 51, 51.5, 52, 52.5, 53, 53.5, 54, 54.5, 55, 55.5, 56, 57, 58, 60, 62, 64 h after administration of study medication

  • time of maximum concentration (Tmax)

    48, 49, 50, 50.5, 51, 51.5, 52, 52.5, 53, 53.5, 54, 54.5, 55, 55.5, 56, 57, 58, 60, 62, 64 h after administration of study medication

Secondary Outcomes (2)

  • Oro-cecal transit time (OCT)

    48, 49, 50, 50.5, 51, 51.5, 52, 52.5, 53, 53.5, 54, 54.5, 55, 55.5, 56, 57, 58, 60, 62, 64 h after first administration of study medication

  • Colon transit time (CTT)

    up to 7 days after administration of the study medication

Study Arms (4)

Treatment A

PLACEBO COMPARATOR

Administration of LOP Placebo (0 h, 12 h, 24 h, 36 h, 48 h), Colon Transit (0 h, 12 h, 24 h, 36 h, 48 h), Placebo (0 h, 12 h, 24 h, 36 h, 48 h) and SSP (48 h). To assess WGT, OCT and CTT under placebo condition.

Drug: Loperamide placeboDevice: Colon TransitDrug: SulfasalazineDrug: Placebo of MNTX and NLX

Treatment B

PLACEBO COMPARATOR

Administration of LOP (0 h, 12 h, 24 h, 36 h, 48 h), Colon Transit (0 h, 12 h, 24 h, 36 h, 48 h), Placebo (0 h, 12 h, 24 h, 36 h, 48 h) and SSP (48 h). To assess WGT, OCT and CTT under loperamide-induced obstipation condition.

Drug: LoperamideDevice: Colon TransitDrug: SulfasalazineDrug: Placebo of MNTX and NLX

Treatment C

ACTIVE COMPARATOR

Administration of LOP (0 h, 12 h, 24 h, 36 h, 48 h), Colon Transit (0 h, 12 h, 24 h, 36 h, 48 h), NLX-ER (0 h, 12 h, 24 h, 36 h, 48 h) and SSP (48 h). To describe the effects of repeated-dose naloxone in preventing loperamide-induced delay of WGT, OCT and CTT and measure pharmacokinetics of naloxone.

Drug: LoperamideDevice: Colon TransitDrug: SulfasalazineDrug: Naloxone

Treatment D

ACTIVE COMPARATOR

Administration of LOP (0 h, 12 h, 24 h, 36 h, 48 h), Colon Transit (0 h, 12 h, 24 h, 36 h, 48 h), MNTX-ER (0 h, 12 h, 24 h, 36 h, 48 h) and SSP (48 h). To describe the effects of repeated-dose methylnaltrexone in preventing loperamide-induced delay of WGT, OCT and CTT and measure pharmacokinetics of methylnaltrexone.

Drug: LoperamideDevice: Colon TransitDrug: SulfasalazineDrug: Methylnaltrexone

Interventions

Loperamide placeboDRUG

200 ml apple juice

Also known as: LOP Placebo
Treatment A
LoperamideDRUG

20 ml Loperamid-ratiopharm® Lösung (ratiopharm) in 180 ml apple juice containing 4 mg of loperamide hydrochloride (prepared before administration)

Also known as: LOP
Treatment BTreatment CTreatment D
Colon TransitDEVICE

5 capsules containing radio-opaque markers of different shapes, respectively

Treatment ATreatment BTreatment CTreatment D
SulfasalazineDRUG

Azulfidine® Tabletten 500 mg (Pharmacia/Pfizer) containing 500 mg immediate release sulfasalazine

Also known as: SSP
Treatment ATreatment BTreatment CTreatment D
Placebo of MNTX and NLXDRUG

Placebo capsule (hard gelatine capsule containing multiple sugar spheres)

Also known as: Placebo
Treatment ATreatment B
NaloxoneDRUG

Naloxone hydrochloride 20 mg Extended Release Capsule equivalent to 18 mg naloxone (hard gelatine capsule containing a single NLX-ER tablet and multiple sugar spheres)

Also known as: NLX-ER
Treatment C
MethylnaltrexoneDRUG

Methylnaltrexone bromide 150 mg extended release capsule equivalent to 122 mg methylnaltrexone (hard gelatine capsule containing multiple MNTX-ER micro tablets)

Also known as: MNTX-ER
Treatment D

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • age: 18 - 45 years
  • sex: male and female
  • ethnic origin: Caucasian
  • minimal body weight: 62 kg
  • body mass index:\> 19 kg/m² and \< 27 kg/m²
  • good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which were judged by the clinical investigator not to differ in a clinical relevant way from the normal state
  • written informed consent

You may not qualify if:

  • hepatic and renal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the study medication
  • gastrointestinal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the study medication
  • drug or alcohol dependence
  • positive drug or alcohol screening
  • smokers of 10 or more cigarettes per day
  • positive results in HIV, HBV and HCV screenings
  • volunteers who are on a diet which could affect the pharmacokinetics of the drug
  • heavy tea or coffee drinkers (more than 1L per day)
  • lactation, pregnancy test positive or not performed or women of child-bearing age without safe contraception
  • volunteers suspected or known not to follow instructions of the clinical investigators
  • volunteers who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
  • volunteers liable to orthostatic dysregulation, fainting, or blackouts
  • participation in a clinical trial during the last 3 months prior to the start of the study
  • less than 14 days after last acute disease
  • less than 3 months after last blood donation
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald

Greifswald, Mecklenburg-Vorpommern, Germany

Location

MeSH Terms

Conditions

Intestinal Obstruction

Interventions

LoperamideSulfasalazineNaloxonemethylnaltrexone

Condition Hierarchy (Ancestors)

Intestinal DiseasesGastrointestinal DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

PiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsSulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsMorphinansOpiate AlkaloidsAlkaloidsHeterocyclic Compounds, Bridged-RingHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingPhenanthrenesPolycyclic Aromatic HydrocarbonsPolycyclic Compounds

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 7, 2012

First Posted

May 11, 2012

Study Start

May 1, 2011

Primary Completion

July 1, 2011

Study Completion

January 1, 2012

Last Updated

May 11, 2012

Record last verified: 2012-05

Locations

DE(1)