Clinical trial NCT02496143: A Safety and PK Study of EC-18 in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chemotherapy-induced Neutropenia
Keywords: Healthy Volunteers
Phase I
Placebo controlled
Single Ascending Dose
PK
Oral administration
Softgel
Lead sponsor: Enzychem Lifesciences Corporation
Sponsor class: INDUSTRY
First posted: 2015-07-14
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 30 days
Secondary outcomes:
measure: To determine the composite pharmacokinetic (PK) parameters of EC-18 following sngle oral doses. AUC0-t, AUC0-24, Cmax, Tmax, 48-hour time period.
timeFrame: Predose [0], 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 hours post dose
Other outcomes:
measure: To determine the pharmacodynamic effects of EC-18 on circulating leukocyte cell counts.
timeFrame: Day 5 after dosing.
measure: To determine the pharmacodynamic effects of EC-18 on red blood cell counts.
timeFrame: Day 5 after dosing.
measure: To determine the pharmacodynamic effects of EC-18 on reticulocyte counts.
timeFrame: Day 5 after dosing.
measure: To determine the pharmacodynamic effects of EC-18 on platelet counts.
timeFrame: Day 5 after dosing.
Locations:
city: Raleigh
country: United States
facility: Carolina Phase I Clinical Research
state: North Carolina
Study officials:
affiliation: Wake Research Associates
name: Treva W Tyson, MD
role: PRINCIPAL_INVESTIGATOR
References: