A Safety and PK Study of EC-18 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine if EC-18 is safe and tolerable in healthy subjects.

Detailed Description
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This will be a randomized, double-blind, placebo-controlled study of the safety, tolerability, PK, and pharmacodynamics of single ascending doses of EC-18 or placebo. If no dose limiting toxicity (DLT) is observed in Cohort One, the dose of EC-18 will be increased to in Cohorts Two, Three, and Four, respectively. Dose escalation to each successive cohort of subjects will not occur until a review of the safety and tolerability data from the previous cohort is completed and the Investigator, Sponsor, and study Medical Monitor together confirm the safety and tolerability of EC-18 given at that dose level.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral Administration of EC-18 in Healthy Subjects

Conditions
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Chemotherapy-induced Neutropenia

Intervention / Treatment
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* Drug: EC-18
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females of childbearing potential must use an acceptable birth control method throughout the study and for 14 days after the dose of study drug. Females of non-childbearing potential (defined as surgically sterilized [tubal ligation/hysterectomy/bilateral salpingo-oophorectomy] or postmenopausal for >2 years) with a negative urine human chorionic gonadotropin pregnancy test at the Screening Visit. Males willing to practice contraception (condom + spermicide) during the study and for 14 days after completion of the study, or who have a female partner using barrier or oral contraception during that timeframe. Body mass index (BMI) between 18 and 32 kg/m2, inclusive. Ability to understand and give informed consent and provide authorization for use of protected health information (Health Insurance Portability and Accountability Act). Willing and able to be confined to the research clinic as required by the protocol. Exclusion Criteria: Febrile (temperature ≥99.5°F/37.5°C) at the Screening Visit or at admission to the research clinic on Day -1. Clinically significant laboratory findings at the Screening Visit defined as the following: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin >1.5 x upper limit of normal (ULN) Blood urea nitrogen (BUN), creatinine >1.25 x ULN White blood cell (WBC) count <0.9 x lower limit of normal (LLN) or >1.1 x ULN Hemoglobin or hematocrit <0.9 x LLN or >1.1 x ULN Platelet count <0.9 x LLN or >1.1 x ULN Glucose <0.9 x LLN or >1.25 x ULN Thyroid-stimulating hormone (TSH) <0.75 x LLN or >1.25 x ULN or any other laboratory, ECG, vital sign, or physical abnormality that, in the investigator's opinion, unfavorably increases the risk of study participation. Positivity for human immunodeficiency virus (HIV) or receiving active antiretroviral therapy, hepatitis B surface antigen positivity, or hepatitis C positivity. History of drug or alcohol abuse within the past 2 years. Females who are pregnant or intend to get pregnant over the next month. Positive urine pregnancy test at the Screening Visit or at admission to the research clinic on Day -1. Positive urine drug or breath alcohol test at the Screening Visit or at admission to the research clinic on Day -1. Subjects should be instructed not to drink alcohol within 12 hours of the screening assessment. Intake of alcohol within 72 hours prior to study drug administration or intake of grapefruit or Seville oranges within 7 days prior to the administration of study drug. Strenuous physical exercise within 48 hours prior to study drug administration. Administration of any over-the-counter medication, dietary supplements, or vitamins within 7 days prior to study drug administration. Excluded from this list is nondaily use of acetaminophen at doses of ≤2 grams over a 24-hour period. Administration of prescription drugs or herbal supplements within 14 days prior to study drug administration. -.Exposure to any investigational agent within 30 days prior to the Screening Visit. Any current medical illness, signs, or symptoms that, in the investigator's opinion, could adversely affect subject safety or study integrity.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>500 mg EC-18 dose or placebo | Drug: EC-18<br>* EC-18 will be supplied as 500 mg Softgel capsules. The study will include up to four sequential dose cohorts. Six subjects in each cohort will be randomized to receive EC-18: 500, 1000, 2000, or 4000 mg by oral administration of 1, 2, 4, and 8 EC-18 capsules, for Cohorts 1, 2, 3 or 4, respectively.<br>* Other names: EC-18 Softgel capsule;Drug: Placebo<br>* Placebo will be supplied as Softgel capsules. The study will include up to four sequential dose cohorts. Two subjects in each cohort will be randomized to placebo and will receive 1, 2, 4 or 8 placebo capsules for Cohorts 1, 2, 3 or 4, respectively.<br>|
| Experimental: Cohort 2<br>1000 mg EC-18 dose orplacebo | Drug: EC-18<br>* EC-18 will be supplied as 500 mg Softgel capsules. The study will include up to four sequential dose cohorts. Six subjects in each cohort will be randomized to receive EC-18: 500, 1000, 2000, or 4000 mg by oral administration of 1, 2, 4, and 8 EC-18 capsules, for Cohorts 1, 2, 3 or 4, respectively.<br>* Other names: EC-18 Softgel capsule;Drug: Placebo<br>* Placebo will be supplied as Softgel capsules. The study will include up to four sequential dose cohorts. Two subjects in each cohort will be randomized to placebo and will receive 1, 2, 4 or 8 placebo capsules for Cohorts 1, 2, 3 or 4, respectively.<br>|
| Experimental: Cohort 3<br>2000 mg EC-18 dose or placebo | Drug: EC-18<br>* EC-18 will be supplied as 500 mg Softgel capsules. The study will include up to four sequential dose cohorts. Six subjects in each cohort will be randomized to receive EC-18: 500, 1000, 2000, or 4000 mg by oral administration of 1, 2, 4, and 8 EC-18 capsules, for Cohorts 1, 2, 3 or 4, respectively.<br>* Other names: EC-18 Softgel capsule;Drug: Placebo<br>* Placebo will be supplied as Softgel capsules. The study will include up to four sequential dose cohorts. Two subjects in each cohort will be randomized to placebo and will receive 1, 2, 4 or 8 placebo capsules for Cohorts 1, 2, 3 or 4, respectively.<br>|
| Experimental: Cohort 4<br>4000 mg EC-18 dose or placebo | Drug: EC-18<br>* EC-18 will be supplied as 500 mg Softgel capsules. The study will include up to four sequential dose cohorts. Six subjects in each cohort will be randomized to receive EC-18: 500, 1000, 2000, or 4000 mg by oral administration of 1, 2, 4, and 8 EC-18 capsules, for Cohorts 1, 2, 3 or 4, respectively.<br>* Other names: EC-18 Softgel capsule;Drug: Placebo<br>* Placebo will be supplied as Softgel capsules. The study will include up to four sequential dose cohorts. Two subjects in each cohort will be randomized to placebo and will receive 1, 2, 4 or 8 placebo capsules for Cohorts 1, 2, 3 or 4, respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of the study will be the number and severity of treatment emergent adverse events (TEAEs) following single doses of EC-18 and placebo. |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the composite pharmacokinetic (PK) parameters of EC-18 following sngle oral doses. AUC0-t, AUC0-24, Cmax, Tmax, 48-hour time period. | AUC0-t: Area under the plasma drug concentration versus time curve from time zero to time t; AUC0-24: Area under the plasma concentration versus time curve from time zero to 24 hours after dosing, Cmax: Maximum observed plasma drug concentration; Tmax: Time of maximum drug concentration | Predose [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PK, Healthy Volunteers, Phase I, Placebo controlled, Single Ascending Dose, Oral administration, Softgel