Pharmacokinetics and Bioavailability of Single Subcutaneous Doses of Methylnaltrexone Versus Intravenous Dose

Study Overview
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Brief Summary
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This is an open-label, Phase I study. Study treatments will entail a four-way crossover among three single, ascending, subcutaneous doses and one intravenous dose of MNTX in six healthy normal male volunteers. Blood samples will be obtained to determine plasma pharmacokinetics, dose proportionality for subcutaneous doses, and absolute bioavailability versus an intravenous dose.

Official Title
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An Open-Label, Phase I Study of the Pharmacokinetics and Bioavailability of Single, Ascending Subcutaneous Doses of Methylnaltrexone Versus Intravenous Dose in Normal, Healthy Male Volunteers

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: SC Methylnaltrexone (MNTX)
* Drug: SC Methylnaltrexone (MNTX)
* Drug: SC Methylnaltrexone (MNTX)
* Drug: IV Methylnaltrexone (MNTX)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject weight between 60 and 80 kg Subject a non-smoker Subject in good physical health, based on history, physical exam, appropriate laboratory and diagnostics tests at screening with no evidence of clinically significant chronic medical condition. Exclusion Criteria: Subject with known hypersensitivity to methylnaltrexone, naltrexon or other opioids Subject consuming any prescription medication within the past two weeks, over-the-counter (OTC) products within seven days, any experimental medication within 30 days prior to study screening, or of any drug with a half-life longer then three days within 10 half-lives (>30 days) of screening Subject consuming barbiturates or other inducers or inhibitors of CYP450 within 3 months of screening Subject with history or evidence of cardiovascular, gastrointestinal, hepatic, neurological, pulmonary, and renal or other significant chronic illness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: SC Methylnaltrexone (MNTX)<br>* Dose 1<br>|
| Experimental: Arm 2<br> | Drug: SC Methylnaltrexone (MNTX)<br>* Dose 2<br>|
| Experimental: Arm 3<br> | Drug: SC Methylnaltrexone (MNTX)<br>* Dose 3<br>|
| Experimental: Arm 4<br> | Drug: IV Methylnaltrexone (MNTX)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration of MNTX | The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects. | 32 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum Plasma Concentration (Tmax) of MNTX | The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects. | 32 days | 
| Clearance of MNTX | The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects. | 32 days | 
| Half-live of MNTX | The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects. | 32 days | 
| Volume of Distribution of MNTX | The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects. | 32 days | 
| Area Under the Plasma Concentration versus Time Curve (AUC) of MNTX | The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects. | 32 days | 
| Urinary Clearance of MNTX | The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects. | 32 days | 
| Percentage of MNTX Excreted in Urine | The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects. | 32 days |