Safety, Pharmacokinetics, Bioavailability, Food Effect, Drug-Drug Interaction Study of APX001 Administered Orally

Study Overview
=================
Brief Summary
-----------------
This is a Phase l double-blind, placebo-controlled, randomized study to investigate the safety, tolerability, pharmacokinetics, bioavailability and food effect of single doses of APX001 administered intravenously and orally, followed by an evaluation of the safety, tolerability, pharmacokinetics and drug-drug interaction potential of multiple doses of APX001 administered orally.

Official Title
-----------------
A Phase 1, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of APX001, to Investigate the Effect of Food on APX001 and to Investigate the Drug-Drug Interaction Potential of APX001

Conditions
-----------------
Fungal Infection

Intervention / Treatment
-----------------
* Drug: APX001 single IV dose
* Drug: APX001 single oral dose 1
* Drug: APX001 single oral dose 2
* Drug: APX001 single oral dose 3
* Drug: APX001 single oral dose fasted
* Drug: APX001 single oral dose fed
* Drug: APX001 multiple oral doses 1
* Drug: APX001 multiple oral doses 2
* Drug: APX001 multiple oral doses 3
* Drug: Cytochrome P450 substrates
* Drug: Matching placebo control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women of childbearing potential must agree to avoid pregnancy during the study and to use contraception at least 2 weeks before the start of the study until 3 months after the last dose of study drug. Males with partner(s) of childbearing potential must agree to use appropriate barrier contraception from the screening period until 3 months after the last dose of study drug. Screening hematology, clinical chemistry, coagulation and urinalysis consistent with overall good health. No significantly abnormal findings on physical examination, ECG and vital signs. Willing and able to provide written informed consent. Exclusion Criteria: Any uncontrolled or active major systemic disease including, but not limited to: cardiovascular, pulmonary, gastrointestinal, metabolic, urogenital, neurological, immunological, psychiatric, or neoplastic disorder with metastatic potential. History or presence of malignancy within the past year. Subjects who have been successfully treated with no recurrence of basal cell carcinoma of the skin or carcinoma in-situ of the cervix may be enrolled. Use of prescription medication within 14 days prior to the first dose of study drug and throughout the study. Use of non-prescription or over-the-counter medications within 7 days prior to the first dose of study drug and throughout the study. Positive results on any of the following Screening laboratory tests: serum pregnancy test, urine alcohol test, urine drugs of abuse, hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1a, Period A<br>single intravenous dose, crossover | Drug: APX001 single IV dose<br> <br> Drug: Matching placebo control<br> <br> |
| Experimental: Cohort 1a, Period B<br>single oral dose, crossover | Drug: APX001 single oral dose 1<br> <br> Drug: Matching placebo control<br> <br> |
| Experimental: Cohort 1a, Period C<br>single oral dose | Drug: APX001 single oral dose 2<br> <br> Drug: Matching placebo control<br> <br> |
| Experimental: Cohort 1a, Period D<br>single oral dose, crossover | Drug: APX001 single oral dose 3<br> <br> Drug: Matching placebo control<br> <br> |
| Experimental: Cohort 1b, Period E<br>Single oral dose under fasted conditions, crossover | Drug: APX001 single oral dose fasted<br> <br> Drug: Matching placebo control<br> <br> |
| Experimental: Cohort 1b, Period F<br>Single oral dose under fed conditions, crossover | Drug: APX001 single oral dose fed<br> <br> Drug: Matching placebo control<br> <br> |
| Experimental: Cohort 2<br>Multiple oral doses | Drug: APX001 multiple oral doses 1<br> <br> Drug: Matching placebo control<br> <br> |
| Experimental: Cohort 3<br>Multiple oral doses | Drug: APX001 multiple oral doses 2<br> <br> Drug: Matching placebo control<br> <br> |
| Experimental: Cohort 4<br>Multiple oral doses in presence of CYP probe substrates | Drug: APX001 single IV dose<br> <br> Drug: APX001 multiple oral doses 3<br> <br> Drug: Cytochrome P450 substrates<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of single and multiple oral doses of APX001 as measured by adverse events (AEs), physical examinations (PE), vital signs (VS), laboratory safety tests, urinalysis and 12-lead electrocardiograms (ECG). |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of single and multiple doses of APX001 as measured by maximum observed concentration (Cmax). |  | 21 days | 
| Pharmacokinetics of single and multiple dose of APX001 as measured by area under the curve (AUC). |  | 21 days | 
| Pharmacokinetics of single and multiple doses of APX001 as measured by terminal half life (t1/2). |  | 21 days | 
| Pharmacokinetics of single and multiple doses of APX001 as measured by volume of distribution (Vd). |  | 21 days | 
| Pharmacokinetics of single and multiple doses of APX001 as measured by elimination rate constant (Kel). |  | 21 days | 
| Pharmacokinetics of single and multiple doses of APX001 as measured by accumulation ratio. |  | 21 days |