Trial Information

Urinary Excretion of Acetylamantadine by Normal Healthy Volunteers

A group of 20 female and 20 male normal healthy volunteers ages 18 to 69 will be recruited
from the community by use of a general advertisement placed initially as posters.

We will tell the volunteers that we are conducting this study in healthy volunteers to
determine how amantadine is eliminated from the body. We will explain the pharmacology of
amantadine and the potential side effects of a single dose before we obtain consent.
Volunteers will be told of the potential for concurrent alcohol ingestion to result in the
presence of acetylamantadine in urine. Volunteers will be required to abstain from alcohol
consumption for at least one day prior to and including the time involved in the amantadine
ingestion and urine collection. Any previous adverse reaction to amantadine will exclude a
person from volunteering from this study. Subjects will be informed that side effects from
this drug ingestion are highly unlikely because only a single dose will be administered.
Any side effects if they occur will be related to the effect of amantadine on the brain.
These effects may include insomnia, jitteriness, difficulty in concentrating and mental
depression. However, these are the side effects associated with chronic ingestion of
amantadine and are highly unlikely to occur with ingestion of a single dose. Once consent
is obtained, the volunteers will ingest a therapeutic dose of amantadine (200 mg) in the
morning, at least 2 hours before breakfast, and their complete urine will be collected over
a period of 12 hours post dose. A previous clinical study in our laboratory with collections
of urine for a total of 8 hours demonstrated that this collection time was sufficient to
collect all metabolically produced acetylamantadine in the urine. The urine samples will
also be analyzed for their content of creatinine as an indication of the completeness of the
urine collection. The urines will then be labeled with a code and frozen at -20°C until
analyzed. The urine will be analyzed for acetylamantidine by our established gas
chromatography method. The technician analyzing the samples will not have access to any
participant information other then the code on the label. Saliva specimens will also be
collected at 2 hour intervals after amantadine ingestion. It should be noted that with the
morning dose of amantadine collection of multiple saliva samples will be simplified and
allow for the determination of the optimal time after dose for the urine analysis.
Furthermore, this design will identify the window of opportunity to give the best signal to
noise ratio for acetylamantidine production. Blood samples will be collected 1 hour prior to
dosing and 2 hours post dose.

We will also collect the following data from each volunteer: their name, age, sex, body
weight, height, any concurrent medication use, and a recent history of alcohol ingestion.
These data will be used for correlation analyses to determine any relationship of urinary
acetylamantidine to the particular cancer diagnosis, sex, and/or the history of alcohol
consumption. All of these data will be coded by the principal investigator, and
individually identifying information locked in a secure cabinet. Access to the data by
other than the principal investigator and/or their attending physician will not be allowed.

Exclusion criteria are anyone with a history of previous adverse reaction to amantadine as
well as pregnant or lactating females will be excluded from volunteering for this study.

Cross validation of the finding will occur by high performance liquid chromatography (HPLC)
of these urine samples for the presence of polyamines and metabolites, including
N1-acetylspermidine.