Pharmacokinetics, Safety, and Tolerability of Methylnaltrexone (MNTX) in Subjects With Impaired Renal Function

Study Overview
=================
Brief Summary
-----------------
This study is evaluating the Pharmacokinetics of MNTX in healthy control subjects and in patients with mild, moderate, or severe renal impairment who do not require hemodialysis.

Official Title
-----------------
A Phase 1, Open-Label Study to Evaluate Single Dose Pharmacokinetics, Safety, and Tolerability of Methylnaltrexone (MNTX) in Subjects With Impaired Renal Function

Conditions
-----------------
Renal Impairment

Intervention / Treatment
-----------------
* Drug: Methylnaltrexone (MNTX)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body weight >100 lbs. (> 45 kg), and body mass index (BMI) between 18-38 kg/m2, inclusive (BMI 18-30 for the matched reference group) For patients/subjects requiring pharmacotherapy, a stable drug regimen, defined as not having started a new drug or changed dosage within three (3) days or five (5) half-lives (whichever was longer) prior to administration of MNTX concomitant medication must either have conformed to the list of approved drugs and dosage or have been approved by the sponsor. Patients with normal renal function, demographically comparable to the patients with impaired renal function weights and ages were within the range of chronic kidney disease (CKD) group and the average for the matched reference group was within 10 years and 10 kg of the average for the CKD Patients with impaired renal function, good general health except for those illnesses associated with CKD. Exclusion Criteria: Subjects/patients with any conditions possibly affecting drug absorption (eg. Gastrectomy or clinically significant diabetic gastroenteropathy) Methadone use Consumption of grapefruit or grapefruit juice within seven (7) days prior to administration of study medication. Patients requiring hemodialysis.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>SC Methylnaltrexone (MNTX) | Drug: Methylnaltrexone (MNTX)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of MNTX in patients with impaired renal function compared to healthy subjects | To compare the PK of MNTX administered subcutaneously as a single dose in patients with impaired renal function with the PK of MNTX administered to healthy subjects. | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak time of maximum concentration (Tmax) of MNTX in patients with impaired renal function compared to healthy subjects | To compare the PK of MNTX administered subcutaneously as a single dose in patients with impaired renal function with the PK of MNTX administered to healthy subjects. | 6 days | 
| Area under the plasma concentration (AUC) of MNTX in patients with impaired renal function compared to healthy subjects | To compare the PK of MNTX administered subcutaneously as a single dose in patients with impaired renal function with the PK of MNTX administered to healthy subjects. | 6 days | 
| Percent of dose excreted in urine of MNTX in patients with impaired renal function compared to healthy subjects | To compare the PK of MNTX administered subcutaneously as a single dose in patients with impaired renal function with the PK of MNTX administered to healthy subjects. | 6 days | 
| Urinary clearance of MNTX in patients with impaired renal function compared to healthy subjects | To compare the PK of MNTX administered subcutaneously as a single dose in patients with impaired renal function with the PK of MNTX administered to healthy subjects. | 6 days |