Safety and PK of MBX-400 (Cyclopropavir) in Normal Volunteers

Cytomegalovirus (CMV) is a common cause of viral illness in children and adults. CMV is also
an important congenital infection with complications including deafness, developmental delay,
and cerebral palsy. The proposed study design is a standard multiple ascending dose
escalation study. Four cohorts of 8 subjects each (6 active; 2 placebo) will be enrolled
sequentially. MBX-400 will be administered orally once daily for 7 days, in the form of
capsules, by study staff while the subject is an inpatient in a research unit. The study
doses will be 100, 350, 750, and 1,000 mg daily. Up to 32 healthy male and female
(non-pregnant, non-lactating) volunteers ages 18-65 in one site, 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 sequential cohorts groups: Cohort 1 will
receive 100 mg PO once daily for 7 days, Cohort 2 will receive 350 mg PO once daily for 7
days, Cohort 3 will receive 750 mg PO once daily for 7 days, and Cohort 4 will receive 1000
mg PO once daily for 7 days of MBX-400. Two members of each cohort will receive placebo. The
study duration for each subject is expected to be approximately 80 days (screening period,
administration of daily dose, and follow-up). Each subject may be admitted to the unit 1 day
prior to the first dose, and will remain in the unit until the day after the 7th daily dose.
Subjects will return for follow-up visits after the last dose. Safety, tolerability, and
pharmacokinetics will be assessed. The overall study duration across all study groups is
expected to be approximately 18 months. The primary objective evaluate the safety and
tolerability of multiple ascending doses of 100, 350, 750, and 1000 mg PO once daily for 7
days of MBX-400 in healthy subjects. The secondary objective determine the plasma and urine
pharmacokinetic profile of multiple doses of 100, 350, 750, and 1000 mg PO once daily for 7
days of MBX-400 in healthy subjects.

Inclusion Criteria:

1. Subject is able to provide informed consent; 2. Subject age is between 18 through 65
years of age, inclusive; 3. Good general health as judged by the investigator; 4. Body Mass
Index (BMI) between 18 to 32 kg/m^2; 5. Males or females who have either no capability or
no sexual behavior that could result in fathering or conceiving a child in the future;
Meeting this inclusion criterion would be demonstrated by one of the parameters below:
-Surgical sterilization (vasectomy, tubal ligation, or hysterectomy) -Females who are
post-menopausal, as defined by the absence of menstrual periods for greater than one year
after age 45 without alternate diagnosis (e.g., PCOS) -Absence of any heterosexual activity
except with a partner meeting one of the above criteria; 6. Available and willing to
participate in the study procedures and requirements; Able and willing to stay in a
clinical facility for up to 10 days and return for all visits; swallow the capsules
provided; and have blood and urine collections for the duration of the study. 7.
Non-smoker, former smoker, or former user of nicotine-containing products Former
smoker/user defined as someone who smoked or used nicotine-products one or more times a
week for at least one month who has not smoked for at least 3 months and has not used
nicotine-containing products for at least 1 month and is willing to abstain from
nicotine-containing products during the study; 8. Willing to abstain from alcohol until
after Day 10 visit* and should moderate drinking through study end (less than or equal to 2
drinks/day). Illicit drugs should not be used throughout the study; *the completion of PK
collections 9. Demonstrates knowledge and comprehension of the study by passing a
questionnaire of the study protocol with a score of at least 70%. Anyone not passing the
test initially may retake the test once.

Exclusion Criteria:

1.Have had an acute illness and/or an oral temperature >100.4°F (38°C) within three days
prior to drug dosing; 2.Have any medical disease or condition that, in the opinion of the
site principal investigator or appropriate sub-investigator, is a contraindication to study
participation; Including acute or chronic medical disease or condition, that would place
the subject at an unacceptable risk of injury, render the subject unable to meet the
requirements of the protocol, or may interfere with the evaluation of responses or the
subject's successful completion of this study. 3.Have a known allergy to the components of
MBX-400 or placebo capsules (microcrystalline cellulose, gelatin, titanium dioxide); 4.Have
a history of anaphylaxis or other serious adverse reactions to nucleoside analog
medications; 5.Have an active malignancy or history of metastatic or hematologic
malignancy; 6.Have clinically significant abnormal ECG at screening based on ECG reading by
pre-defined study consulting cardiologist; Including: 1) conduction disturbance (complete
left or complete right bundle branch block or nonspecific intraventricular conduction
disturbance with QRS> / =120ms, PR> / =220ms, any second or third degree AV block, or QTc
prolongation (>450ms); 2) significant repolarization (ST segment or T wave) abnormality; 3)
significant atrial or ventricular arrhythmia; 4) frequent atrial or ventricular ectopy
(e.g., frequent premature atrial contractions, 2 premature ventricular contractions in a
row); 5) ST elevation consistent with ischemia; or 6) evidence of past or evolving
myocardial infarction 7.Have known currently active HIV, CMV, hepatitis B or hepatitis C
infection; 8.Have clinically significant anemia or bleeding disorder; 9.Have clinically
significant gastrointestinal disorder including ulcer disease or conditions affecting
absorption; 10.Have a blood pressure or heart rate that is a Grade > / =1; 11.Have a total
White Blood Cell (WBC) count, Absolute Neutrophil Count (ANC), hemoglobin or platelet count
that is a Grade > / =1 at screening; 12.Have a creatinine higher than the normal range at
screening; 13.Have an Alanine Aminotransferase (ALT) or an Aspartate Aminotransferase (AST)
> Upper Limit of Normal at screening; 14.Have PT or PTT that is a Grade > / =1 at
screening; 15.Have any electrolyte level (sodium, potassium) that is a Grade > / =1 at
screening; 16.Have a value higher than trace for glucose, hemoglobin and/or protein on
urinalysis at screening; 17.Have ongoing drug abuse/dependence (including alcohol) or a
history of this within five years of enrollment; 18.Have any diagnosis, current or past, of
schizophrenia, bipolar disease, or other major psychiatric diagnosis; 19.Have a history of
hospitalization for psychiatric illness, suicide attempt, or confinement for danger to self
or others, within the past 10 years; Subjects with a psychiatric disorder not meeting
exclusion criteria, e.g., attention-deficit hyperactivity disorder, that is controlled for
a minimum of 3 months may be enrolled as long as the investigator has determined that the
subject's mental status will not compromise the subject's ability to comply with protocol.
20.Have donated blood within 30 days prior to Day 1 or plans to donate blood during the
study; 21.Have taken any drug active against herpes viruses within 30 days prior to Day 1
including but not limited to: acyclovir, valacyclovir, famciclovir, penciclovir,
ganciclovir and valganciclovir; 22.Use of any medication on a chronic basis; 23.Use of
alcohol-containing, grapefruit-containing, or caffeine-containing foods or beverages within
72 hours prior to Check-in (Day -1); 24. Are taking or have utilized any drugs within 3
days prior to Day 1; alcohol or tobacco within 3 days prior to Day 1; or are a chronic
alcohol user; Concomitant medications, including prescription and over the counter
medications as well as herbals, vitamins and supplements, are not allowed within 3 days
prior to Day 1. Chronic alcohol user is defined as consuming 10 or more alcoholic drinks
per week. 25.Urine cotinine level >150 ng/mL; 26.Have taken any investigational agents
within 28 days of Day 1; 27.Have a positive urine drug screen.