A Comparative, Pharmacokinetic Study of CB-839 Capsule and Tablet Formulations in Healthy Adults

A new tablet formulation of CB-839 was recently developed in order to enable rapid,
automated manufacturing of CB-839. Previous studies have used a capsule formulation of
CB-839. This study will enable a PK comparison between CB-839 capsules and CB-839 tablets.

This is a Phase 1, comparative, randomized, single-dose, 2-way crossover PK comparability
study of CB-839 administered as capsule and tablet formulations in healthy adult subjects.
Serial blood samples for PK analyses will be collected over a 24 hour period after each
administration of CB-839. All subjects will be monitored for safety throughout their
participation in the study.

Inclusion Criteria:

- Healthy, adult, male or female, 18-55 years of age, inclusive, at screening.

- Has not used nicotine containing products for at least 3 mo prior the first dose.

- Body mass index (BMI) within 18.0 and 30.0 kg/m2, inclusively, at screening.

- Medically healthy with no clinically significant medical history, physical
examination, laboratory profiles, vital signs, or ECGs, as deemed by the Principal
Investigator (PI).

- For a female of childbearing potential: either be sexually inactive (abstinent) for
14 days prior to the first dose and through 14 days following the last dose of study
drug(s) or be using one of the following acceptable birth control methods:

1. Non-hormone releasing intrauterine device in place for at least 3 mo prior to
the first dose of study drug with either a physical (e.g., condom, diaphragm) or
a chemical (e.g., spermicide) barrier method from the time of screening through
14 days following the last dose of study drug.

2. A physical barrier method (e.g., condom, diaphragm) with a chemical barrier
method (e.g., spermicide) for at least 14 days prior to the first dose of study
drug and until 14 days after the last dose of study drug.

- In addition, female subjects of childbearing potential will be advised to remain
sexually inactive or to keep the same birth control method or for at least 14 days
following the last dose of study drug.

- For a female of non-childbearing potential: must have undergone one of the following
sterilization procedures at least 6 mo prior to the first dose of study drug:

1. hysteroscopic sterilization;

2. bilateral tubal ligation or bilateral salpingectomy;

3. non-surgical transcervical sterilization (e.g., Essure®);

4. hysterectomy;

5. bilateral oophorectomy;

6. or be postmenopausal with amenorrhea for at least 1 year prior to the first
CB-839 dose with FSH serum levels consistent with postmenopausal status as per
PI judgment.

- A non-vasectomized, male subject must agree to use a condom with spermicide or
abstain from sexual intercourse during the study until 90 days beyond the last dose
of study drug. (No restrictions are required for a vasectomized male provided his
vasectomy has been performed 4 mo or more prior to study start. A male who has been
vasectomized less than 4 mo prior to study start must follow the same restrictions as
a non-vasectomized male).

- If male, must agree not to donate sperm from dosing until 90 days after the last
dose.

- Understands the study procedures in the informed consent form (ICF) and be willing
and able to comply with the protocol.

Exclusion Criteria:

- Subject is mentally or legally incapacitated or has significant emotional problems at
the time of the screening visit or is expected to manifest significant emotional
problems during the conduct of the study.

- History or presence of clinically significant medical or psychiatric condition or
disease in the opinion of the PI.

- History of any illness that, in the opinion of the PI, might confound the results of
the study or poses an additional risk to the subject by their participation in the
study.

- History or presence of alcoholism or drug abuse within the past 2 years prior to
screening.

- History or presence of hypersensitivity or idiosyncratic reaction to the study drugs
or inactive ingredient(s).

- History or presence of:

1. liver disease, pancreatic insufficiency or intestinal malabsorption;

2. neuropathy or muscle disorders;

3. seizures;

4. asthma;

5. fluid retention;

6. cardiovascular disease, cardiac arrhythmias, hypertension, cardiovascular
thrombotic events, myocardial infarction, or stroke;

7. ulcer disease or gastrointestinal bleeding;

8. renal papillary necrosis and other renal injury;

9. exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal
necrolysis.

- Female subjects who are pregnant or lactating.

- Positive urine drug or alcohol results at screening or check-in.

- Positive urine cotinine at screening.

- Positive results at screening for HIV types 1 and 2, HBsAg, or HCV.

- Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at
screening.

- Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.

- QTcF interval is > 460 msec (males) or > 480 msec (females) or deemed clinically
abnormal by the PI at screening.

- Estimated creatinine clearance < 90 mL/min at screening.

- Unable to refrain from or anticipates the use of:

1. Any non-prescription medications, herbal remedies, or vitamin supplements
beginning 14 days prior to the first dose of study drug and throughout the
study.

2. Any prescription medications (including hormonal contraceptives, hormone
replacement therapy, and lithium) beginning 14 days prior to the first dose of
study drug and throughout the study.

3. Proton pump inhibitors (PPIs) beginning 14 days prior to the first dose of study
drug and throughout the study.

- Has been on a diet incompatible with the on-study diet (in the opinion of the PI)
within the 28 days prior to the first dose of study drug, and throughout the study.

- Donation of blood or significant blood loss within 56 days prior to the first dose of
study drug.

- Plasma donation within 14 days prior to the first dose of study drug.

- Participation in another clinical trial within 28 days prior to the first dose of
study drug. The 28-day window will be derived from the date of the last blood
collection or dosing, whichever is later, in the previous study to Day 1 of Period 1
of the current study.