Safety, Tolerability, and Pharmacokinetics of Oral BT-11 in Healthy Adult Male and Female Volunteers

Primary outcome: To assess the safety and tolerability of BT-11 after single and multiple
ascending oral dose administration in healthy volunteers

The safety and tolerability profile of BT-11 as evidenced by the occurrence, timing,
frequency, and severity of adverse events (AE) and clinically significant:

- laboratory abnormalities Haematology, Coagulation, Serum Chemistry, Urinalysis, HIV,
HBsAg, HCV

- physical exam findings Complete physical exam include, at a minimum, assessment of the
following systems: skin, head, ears, eyes, nose and throat, respiratory system,
cardiovascular system, gastrointestinal system, neurological condition, blood and
lymphatic systems, and the musculoskeletal system

- 12-lead ECG aberrations ECG data (RR, PR, QRS, QT and QTcF intervals and pulse rate)

- and/or vital signs abnormalities Vital signs assessments will include systolic and
diastolic blood pressure, pulse, tympanic body temperature, and respirations

Timepoint: Adverse events will be recorded from the time of first dosing through to end of
study date.

Laboratory abnormalities at the screening visit, up to 28 days prior to the first dose of
study medication then up to end of study visit.

Physical Exam findings will be collected at screening, Day-1 and Day 2 for the single
ascending dose. For multiple ascending dose it will be collected at screening, Day-1, Day 3,
Day 5 and Day 7

12-lead ECG aberrations will be collected from Screening then on Day -1 and Day 2 for the
single ascending dose. For MAD it will be collected at screening, Day-1, Day 3, Day 5 and Day
7

Vital signs abnormalities collected from Screening then on Day -1 and Day 2 for the single
ascending dose. For MAD it will be collected at screening, Day-1, Day 3, Day 5 and Day 7

Primary outcome: To assess the safety and tolerability of BT-11 after single and multiple
ascending oral dose administration in healthy volunteers.

Timepoint: For single ascending dose blood samples for PK analysis will be collected pre-dose
and at 15, 30, 45 minutes, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose

Urine samples for PK analysis will be collected pre-dose and 0-24 hours post-dose;

For multiple ascending blood samples for PK analysis will be collected pre-dose and at 15,
30, and 45 min and 1, 1.25 1.5, 2, 3, 4, 6, 8, 10, 12 and 18 hours post Day 1 dose. Pre-dose
on Day 2

Urine samples for PK analysis will be collected on Day 1, pre-dose and at 0-24 hours
post-dose

On follow up period, Day 3 to Day 6, Plasma samples for PK analysis will be collected
pre-dose on each day.

Secondary outcome: The following PK parameters will be determined:

- Time to maximum concentration (tmax);

- Maximum concentration (Cmax);

- Area under the concentration-time curve from time 0 to last measurable time-point
(AUC0-tlast);

- Area under the concentration-time curve from time 0 to infinity (AUC0-inf);

- Terminal Elimination Rate Constant (kel);

- Terminal half-life (t1/2);

- Terminal clearance (CL/F);

- Volume of distribution (Vd/F).

Timepoint: The following PK parameters will be determined for single ascending dose:

Area under the concentration-time curve from time 0 to 24 hours from start of first dose
(AUC0-24h);

• Amount of drug excreted in urine in each collection interval

For the multiple ascending dose:

Area under the concentration-time curve from time 0 to 24 hours from start dosing (AUC0-24h)
on Day 1 and 0 to 24 hours (AUC0-24h) following the last dose on Day 7;

- Pre-dose trough on Days 2, 3, 4, 5 and 6;

- Amount of drug excreted in urine in each collection interval;

- Volume of distribution at steady state (Vss/F).

Inclusion Criteria:

1. Healthy male and female volunteers aged 18 to 65 years, inclusive.

2. Body weight 65 - 85 kg.

3. Body Mass Index (weight in kg divided by square of height in meters) 19-31 kg/m2,
inclusive.

4. Male volunteers must agree to abstain, between dosing and 30 days post-dosing, from
sexual intercourse with pregnant or lactating women and, if sexually active with a
female partner, to use a condom in addition to his female partner's use of another
form of contraception (e.g., IUD, diaphragm, oral contraceptive, injectable
progesterone contraceptive, subdermal implant contraceptive, or tubal ligation). A
male practicing abstinence is also acceptable.

5. Female subjects of child-bearing potential, with a fertile male sexual partner, should
be willing to use adequate contraception from Day 1 until 30 days after the follow-up
visit. Adequate contraception is defined as an intrauterine device combined with at
least one of the following forms of contraception: a diaphragm or cervical cap, or a
condom. Also, total abstinence, in accordance with the lifestyle of the subject, is
acceptable.

6. Volunteer agrees not to take any concomitant medications, including prescriptions or
over-the-counter (OTC) medications during the interval from 3 days prior to dosing
until after the last PK blood draw for the study.

7. Volunteer agrees not to consume alcohol during the interval from 3 days prior to
dosing until after the last PK blood draw for the study.

8. Volunteer is able to communicate effectively with study personnel.

9. Volunteer is able to understand and comply with protocol and investigative site
requirements, instructions, and restrictions.

10. Volunteer has read, confirmed understanding of, and signed the written informed
consent form after the nature of the study and all essential elements of the informed
consent document have been fully explained and all of the Volunteer's questions have
been answered to his or her satisfaction, prior to initiation of any study procedures.

Exclusion Criteria:

1. Any clinically significant abnormality identified in the screening history, physical
examination (including Vital Signs), laboratory testing, or electrocardiographic
testing. Repeat testing of vital signs to confirm the value is allowed. Up to two
repeat tests are permitted to confirm eligibility.

2. An excessive fall in blood pressure on orthostatic testing at screening or Day -1
(i.e., a fall in systolic blood pressure > 25 mmHg or in diastolic blood pressure > 15
mmHg).

3. Any 12-lead ECG finding at screening or on Day -1 that may, in the opinion of the
Investigator, compromise interpretation of ECGs for cardiac safety assessment or
complicate interpretation of events that may occur post-dose (e.g., QT not accurately
measurable, conduction abnormalities)

4. Positive test for HIV, hepatitis B surface antigen, or hepatitis C antibody.

5. Any clinically significant cardiac, pulmonary, renal, metabolic, neurologic, or other
medical, behavioural, or genetic condition.

6. Any condition that places the volunteer at significantly increased risk or may risk
compromise of study objectives.

7. Use of prescription or non-prescription drugs 3 days or 5 half-lives (whichever is
longer) prior to dosing to after last PK draw.

8. Use of herbal supplements within 3 days or 5 half-lives (whichever is longer) prior to
the first dose of study drug to after last PK draw.

9. Use of alcohol within 72 hours prior to first dose of study drug.

10. History of drug or alcohol abuse (by DSM-IV definition) within 3 months prior to
screening.

11. Positive urine drug screen (including cotinine, cannabis, cocaine, opiates,
amphetamines, and other tests as determined by Investigator). Repeating analyses will
be allowed if the PI suspects that there might be false positive results.

12. Volunteer has a contraindication to blood sampling or is considered to have
insufficient peripheral venous access.

13. Volunteer has donated blood or blood products in volumes of 450 mL or more within 30
days prior to study enrollment.

14. Volunteer has been previously exposed to BT-11.

15. Volunteer has participated in a study of any investigational drug, device, biologic,
or other agent within 30 days prior to study enrollment.

16. Volunteer has known hypersensitivity to BT-11 or any of its constituents.

17. Volunteer has any disorder (e.g., psychiatric, addictive) that, in Investigator's
judgement, may compromise his/her ability to provide legal written informed consent.