Evaluating the Safety and Plasma Levels of N-Methanocarbathymidine (N-MCT) in Normal Patients
Evaluating the Safety and Plasma Levels of N-Methanocarbathymidine (N-MCT) in Normal Patients
This Phase I evaluation of N-MCT in normal volunteers requires sequentially increased doses.
 At each dose level, the safety and pharmacokinetic will be measured. This Phase I trial will
 have the dose range of N-MCT from 200mg - 1200mg per patient.
This is a Phase 1 trial evaluating the safety and pharmacokinetics of N-MCT administered
 orally as a single ascending dose. Healthy male and female (non-pregnant, non-lactating)
 subjects ages 18-45, will be consented and allowed to participate in the study if upon
 screening they meet the inclusion / exclusion criteria.

 Subjects will be enrolled into one of four cohort groups sequentially. Each of the six
 subjects in each group will receive doses sequentially within 48 hours between each dose
 increase (ie, the second subject in a group will not receive a dose until 48 hours after the
 first subject received a dose).

 Cohort 1 (6 subjects, male & female) will receive 200 mg, Cohort 2 (6 subjects, male &
 female) will receive 400 mg, Cohort 3 (8 subjects, males and females, 2 placebo, 6 treated)
 will receive 800 mg and Cohort 4 (8 subjects, males and females, 2 placebo, 6 treated) will
 receive 1200 mg of N-MCT.

 Each cohort will be completed and the safety data evaluated prior to initiating the next
 cohort. All subjects will have plasma and urine samples evaluated for N-MCT.

 The PI of the protocol and the IDMC will review safety data (AEs), safety labs, vital signs,
 and findings through Day 7 for Cohort 1 before enrolling subjects in Cohort 2. Cohort 2 data
 through Day 7 will be reviewed accordingly by the PI and IDMC before enrolling subjects in
 Cohort 3. Cohort 3 data through Day 7 will be reviewed by the PI and the IDMC before
 enrolling subjects in Cohort 4.

 However, prior to dose escalation to a new cohort as described above, GHUCCTS IRB will review
 and approve, in expedited review, the IDMC report upon which the decision to escalate the
 dose to a new cohort is based.
Inclusion Criteria:

 Subjects must meet all Inclusion Criteria to be included in the study:

 1. Healthy men and women 18 to 45 years of age, inclusive

 2. Ability to understand the consent process and study procedures

 3. Informed consent obtained and signed

 4. Comprehension of the protocol, as determined by the clinic personnel using a series of
 questions after explaining the procedures.

 5. Subjects agree to be available for all study visits.

 6. General good health, no current medical illness or clinically significant abnormal
 physical examination findings as determined by study physician investigators

 7. Negative past or current history of herpes virus infections, or no current use of
 antiviral medications for the treatment of herpes virus infections

 8. Negative serum pregnancy test at screening and a negative serum pregnancy test on the
 day of admission to the inpatient phase for all female subjects of child bearing
 potential.

 9. Negative urine toxicology screen for marijuana, cocaine, opiates, amphetamines,
 phencyclidine, benzodiazepines, and barbiturates for screening and on the day of
 admission to the inpatient phase.

 10. Negative urine toxicology screen for nicotine (Cotinine) for screening and on the day
 of admission to the inpatient phase.

 11. Negative breath alcohol screen and agreement not to consume alcohol for the duration
 of the study.

 12. Body mass index (BMI) greater than or equal to 18.5 kg/m2 and less than or equal to
 29.9 kg/m2 [weight (kg)]/ [height (m)2].

 13. Agreement by subjects with reproductive potential to use highly effective
 contraception as described in protocol Section 4.1.1.

 14. Willingness to avoid strenuous exercise for at least 72 hours prior to initial study
 drug administration and during the study to Day 7 visit.

 Note: Strenuous physical exercise includes long distance running > 5 km/day, weight
 lifting, or any physical activity to which the subject is not accustomed.

 Exclusion Criteria:

 -  Subjects meeting any of the Exclusion Criteria at Baseline will be excluded from study
 participation.

 1. Medical conditions that preclude participation in the study as determined by the
 study physician investigators.

 Note: Condition that may preclude participation includes:

 1.1. Vital signs that are outside the ranges in the table below, measured after
 at least 10 minutes rest:

 Blood Pressure (BP) 90-140/55-90 mmHg Pulse Rate (PR) 50 100 beats/min Tympanic
 Temperature (T) less than or equal to 37.6ºC Respiration Rate (RR) 12 to 20
 breaths/minute

 1.2. Current diagnosis of pulmonary disease 1.3. Current diagnosis of asthma,
 which has required use of asthma medications within the past year 1.4. History of
 or current diagnosis of diabetes mellitus 1.5. Autoimmune disorder, such as
 systemic lupus erythematosus, Wegener's granulomatosis, rheumatoid arthritis 1.6.
 History of malignancy except low-grade skin cancer (i.e., basal cell carcinoma
 which has been surgically cured) 1.7. Chronic renal, hepatic, or pulmonary
 disease or gastrointestinal tract condition that could interfere with the
 absorption of the study drug (e.g., surgical resection of significant proportions
 of the stomach or bowel, gastric bypass, gastric banding, cholecystectomy,
 irritable bowel syndrome, inflammatory bowel disease) 1.8. History of cardiac
 abnormalities including Wolff-Parkinson-White syndrome, dysrhythmias, or coronary
 artery disease 1.9. History of prolonged QT interval

 2. Clinically significant abnormal electrocardiogram (ECG) at screening in the
 judgment of the investigator.

 3. Screening laboratory values outside the acceptable low and upper limits unless
 deemed NCS by the principal investigator or sub-investigator.

 4. Positive serology results for Hepatitis B surface antigen (HBsAg), or hepatitis C
 virus (HCV) or human immunodeficiency virus (HIV) antibodies

 5. Febrile illness with temperature documented >38°C within 7 days of dosing

 6. Pregnancy or breastfeeding

 7. Known hypersensitivity or allergic reaction(s) to study drug components,
 including ingredients present in the formulation and/or to other nucleoside
 analogue antiviral drugs.

 8. Have consumed any prohibited products or undergone any prohibited procedure
 listed in Table 3 within the indicated time frame.

 9. Lack of ability to fully understand the informed consent. This will be determined
 by the recruiter/interviewer after explaining the consent and observing the
 subject reading the consent.

 10. Use of any form of tobacco, including cigarette smoking, pipe smoking, oral
 tobacco, for 30 days before screening and for the duration of the study.

 11. Any specific condition that, in the judgment of the Investigator, precludes
 participation because it could affect subject safety.