Evaluation of the Attenuation by Aes-103 of Hypoxia Mediated Decrements in Endurance Exercise Performance

This is a randomized, placebo-controlled, double-blind blind, repeated measures (cross-over)
study. Approximately 12 healthy adult men will consume, in a random order, a placebo prior
to exercise in normoxia, a placebo prior to exercise in hypoxia, 1000 mg of Aes-103 prior to
exercise in hypoxia, and 3000 mg of Aes-103 prior to exercise in hypoxia.

Study participants will report to the Human Performance/Clinical Research Laboratory (HPCRL)
on 6 separate occasions. On visit 1 study participants will undergo screening (e.g. medical
history and 12-lead electrocardiogram and blood pressure at rest and during incremental
exercise to volitional exhaustion), and will be instructed to avoid foods and drinks high in
5-HMF (e.g., coffee, malt, barley, dried fruits, and caramel) for at least 3 days before
each subsequent visit. Visit 2 will comprise of a habituation visit during which subjects
will be given the opportunity to rehearse the exercise test. Visits 3, 4, 5 and 6, will
occur in a random order and be almost identical in nature. Study participants will abstain
from vigorous physical exercise and alcohol consumption during the 24-hours prior to each
visit. In addition, study participants will abstain from all food and beverages, except
water, during the 4-hours prior to visits 3, 4, 5 and 6. On arrival subjects will be
instrumented for measurement of heart rate, blood pressure and blood oxygen saturation.
Following baseline determination subjects will consume either: a placebo, 1000 mg of Aes-103
or 3000 mg of Aes-103. 45 minutes after consumption, participants will enter our
environmental chamber, adjusted randomly to either normoxia (21% oxygen) or hypoxia (15%
oxygen). The pairing of normoxia/hypoxia and supplement will be as follows: placebo +
normoxia, placebo + hypoxia, 1000 mg + hypoxia, and 3000 mg + hypoxia. Participants will
remain seated in the environmental chamber for 15 minutes, after which they will complete a
standardized warm-up bout of exercise (100 W for 30 minutes) followed by a brief time trial
(time taken to cycle 12.5 km (~7.75 miles)). Heart rate, blood pressure and blood oxygen
saturation will be recorded every 5 minutes. During exercise, subjective ratings of
perceived exertion (Borg Scale) will be recorded every 10 minutes, and at end-exercise.

Inclusion Criteria:

- Be a healthy male volunteer, aged 18-40 years old, body mass index 18-30 kg/m2,
inclusive

- Have successfully completed a screening visit consisting of medical history, physical
examination, 12-lead ECG, blood pressure, blood oxygen saturation at rest and during
incremental exercise to volitional exhaustion (Note: Subjects with abnormal screening
values may be eligible if the results are not clinically significant, as judged by
the investigator or medical monitor)

- Be able to understand and have provided written informed consent including signature
on an informed consent form approved by an institutional review board

- Have provided written authorization for use and disclosure of protected health
information

- Agree to abide by the study schedule and dietary restrictions and to return for the
required assessments

- Be willing to abstain from foods high in 5-HMF (e.g., coffee, malt, barley, balsamic
vinegar, dried fruits,and caramel products) for at least 3 days prior to each dosing

- Be willing and able to repeatedly perform exhaustive cycle ergometer exercise

Exclusion Criteria:

- Have evidence of clinically significant cardiovascular, respiratory, renal, hepatic,
pulmonary, gastrointestinal, hematological, neurological, psychiatric, or other
disease that may interfere with the objectives of the study or the safety of the
subject, as judged by the investigator in agreement with the sponsor or medical
monitor, have been hospitalized in the past 2 years as a result of these conditions,
or are receiving pharmacological treatment for these conditions

- Have taken prescription drugs or herbal preparations in the 2 weeks before dosing

- Is currently enrolled in another clinical study for another investigational drug or
has taken any other investigational drug within 30 days before the screening visit

- Habitual and/or recent use of recreational drugs, such as cocaine, marijuana,
opiates, amphetamines, methamphetamines, benzodiazepines,

- Have taken disulfiram, 4-methylpyrazole, or any other drug that is an inhibitor of
alcohol dehydrogenase or aldehyde dehydrogenase within the past 30 days

- Have engaged in strenuous physical activity within 24 hours prior to dosing

- Be considered not suitable for participation in this trial for any reason, as judged
by the investigator