Drug Interaction Study of Levoketoconazole and Metformin

This study will enroll healthy male and female subjects to evaluate the effect of
levoketoconazole on the PK of a single 500 mg dose of metformin. There will be 3 sequential
treatment periods, and all subjects will receive metformin only in Period 1, escalating doses
of levoketoconazole in Period 2, and concurrent administration of metformin and
levoketoconazole in Period 3.

Inclusion Criteria:

1. 18-55 years of age, inclusive, at time of consent.

2. Body mass index (BMI) between 18 and 32 kg/m2, inclusive.

3. In good general physical health as determined by absence of clinically significant
medical history, physical examination findings, vital signs, clinical laboratory
evaluations and ECG measurements.

4. Has not consumed and agrees to abstain from taking any prescription drugs, dietary
supplements including vitamins and herbal preparations, or non-prescription drugs
(except as authorized by the Investigator AND Medical Monitor) for 14 days prior to
initial CRU admission on Day -1 and through Follow-Up.

5. Has not consumed alcohol-containing beverages for 3 days prior to initial CRU
admission on Day -1 and agrees not to consume alcohol for the duration of the study
through Follow-Up.

6. Is a nonsmoker (for at least 3 months) with negative urinary cotinine test at
Screening and agrees to abstain from tobacco- and nicotine containing products for the
duration of the study.

Exclusion Criteria:

1. Evidence of any out-of-normal-range laboratory value at Screening that has not been
reviewed, approved, and documented as Not Clinically Significant by the Investigator
(except for LFTs, which must be within the normal range).

2. Concurrent medical illness that would interfere with the conduct of the study in the
opinion of the Investigator.

3. History or presence of clinically significant cardiovascular, pulmonary, hematologic,
endocrine, immunologic, dermatologic, neurologic, psychiatric, renal, hepatic, chronic
respiratory, or gastrointestinal disease as judged by the Investigator.

4. Clinically significant ECG abnormality or confirmed QTcF interval > 450 msec at
Screening or unconfirmed QTcF interval > 450 msec at CRU admission.

5. Family history (parents, siblings, and offspring) of QT interval sudden cardiac death.

6. Positive urine drug screen for drugs-of-abuse, including cocaine, 3,4
methylenedioxy-methamphetamine (MDMA), tetrahydrocannabinol, opioids, benzodiazepines,
amphetamines, and barbiturates, and/or positive urine screen for alcohol at Screening
and CRU admission.

7. Positive urinary cotinine test at Screening.

8. Treatment with an investigational drug within the longer of 30 days or five half-lives
of the investigational drug preceding the first dose of study drug.

9. Positive for Human Immunodeficiency Virus (HIV), hepatitis B, and/or hepatitis C on
Screening assessments.

10. Acute illness within 7 days of the first CRU admission on Day -1.

11. Donated plasma within 7 days of Screening.

12. Donated 1 or more pints of blood (or equivalent blood loss) within 30 days prior to
Screening.

13. History of caffeine consumption exceeding 8 cups of coffee/day (1 cup = 8 fluid
ounces) within 14 days prior to first dose, or consumption of any caffeine- or
chocolate-containing products for 3 days prior to CRU admission each week. Caffeine
containing foods and/or beverages (e.g., tea and cola) should be considered equivalent
to coffee.

14. History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces of
wine, 12 ounces of beer, or 1.5 ounces of hard liquor) within 180 days of Screening.

15. Female subject who is pregnant or lactating.

16. Male with hemoglobin less than 12.0 g/dL; Female with hemoglobin less than 11.0 g/dL.

17. Had difficulties swallowing whole tablets.

18. Body habitus prevents repeated venipuncture.

19. History of hypersensitivity or allergy to metformin.

20. History of hypoglycemia.

21. Participated in the COR-2017-02 levoketoconazole food effect study.

22. History of drug-induced liver injury from any drug.