A First in Human Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics Effects of OC514

Study Overview
=================
Brief Summary
-----------------
Oncocross is developing OC514, a drug-drug combination product containing 2 active pharmaceutical ingredients for cancer cachexia. This study is designed to assess the safety and tolerability of single and multiple oral doses of OC514 in healthy adult volunteers.

Detailed Description
-----------------
This is a single-center study in which a total of 24 subjects will be enrolled into 1 of 3 dose level cohorts in an ascending fashion. Each cohort will consist of 8 subjects randomized to receive OC514 or matching placebo at a ratio of 3:1. Eligible subjects will be admitted to the clinical research unit (CRU) from Day -1 to 5 and again from Day 15 to Day 17 and will be discharged upon completion of post-dose assessment. The subjects will attend the CRU for outpatients visits on Day 8 and Day 12. The subjects will return for a follow-up visit on Day 19 and End of Study visit on Day 21. The total study duration is up to 9 weeks consisting of up to 6 weeks of screening, 2 weeks of blinded treatment, and 1 week of safety follow-up. Safety oversight will be provided by a Safety Review Committee (SRC).

Official Title
-----------------
A Phase 1, Randomized, Double-Blind, Dose-Ranging, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics Effects of OC514 in Healthy Adult Volunteers

Conditions
-----------------
Cancer Cachexia

Intervention / Treatment
-----------------
* Drug: OC514 (Low dose)
* Drug: OC514 (Mid dose)
* Drug: OC514 (High dose)
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male or female volunteers, between 18 and 65 years of age, both inclusive. BMI between 18 and 32 kg/m2 (inclusive) with a bodyweight >/= 50 kg at screening. Medically healthy with no clinically significant medical history. Adequate venous access. Non-pregnant, non-lactating females. Must be able to comply with the requirements of the study. Exclusion Criteria: History of any clinically significant disease or disorder. History or presence of gastrointestinal, hepatic, or renal disease or any other condition or past surgical intervention (eg, cholecystectomy). Has creatinine clearance < 60 mL/min. Any current active infections, including localized infections, or any recent history (within 2 weeks prior to first IP administration) of active infections (including severe acute respiratory syndrome coronavirus 2 [SARS-COV-2]), cough or fever, or a history of recurrent or chronic infections. Lymphoma, leukemia, or any malignancy within the past 5 years except for fully resected basal cell or squamous epithelial carcinomas of the skin that have been fully treated for at least 1 year with no recurrence. Any positive laboratory-confirmed COVID-19 test at Screening or check-in. History of human immunodeficiency virus (HIV) antibody positive or tested positive for HIV; had a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tested positive for HBsAg or anti-HCV at Screening. Had major surgery (general anesthetic) in the last 3 months or minor surgery (local anesthetic) in the last 1 month prior to Screening. History of narrow angle glaucoma. History of benign prostatic hyperplasia (BPH) with lower urinary tract symptoms. Any clinically significant medical or psychiatric condition, medical/surgical procedure, or trauma within 4 weeks prior to the first IP administration. Blood donation within 1 month of Screening or any blood donation/blood loss greater than 500 mL during the 3 months prior to Screening. Abnormal vital signs. Prolonged Fridericia QT correction formula (QTcF) > 450 msec or shortened QTcF < 340 msec or family history of long QT syndrome at the Screening and on Day -1. Positive screen for drugs of abuse or cotinine (≥ 500 ng/mL) or positive screen for alcohol at Screening or admission to the CRU on Day -1. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator, to any components in the IP.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participants will receive either low dose level of OC514 or placebo | Drug: OC514 (Low dose)<br>* Low dose level of OC514<br>* Other names: OC514;Other: Placebo<br>* Placebo to match<br>|
| Experimental: Cohort 2<br>Participants will receive either mid dose level of OC514 or placebo | Drug: OC514 (Mid dose)<br>* Mid dose level of OC514<br>* Other names: OC514;Other: Placebo<br>* Placebo to match<br>|
| Experimental: Cohort 3<br>Participants will receive either high dose level of OC514 or placebo | Drug: OC514 (High dose)<br>* High dose level of OC514<br>* Other names: OC514;Other: Placebo<br>* Placebo to match<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-emergent adverse events (TEAEs) and treatment related TEAEs | TEAEs will be measured as per the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 | Day 1- Day 21 | 
| Severity of TEAEs and treatment related TEAEs | TEAEs will be measured as per the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 | Day 1- Day 21 | 
| Number of participants with abnormal clinically significant laboratory results | Clinical laboratory includes hematology, and biochemistry | Day 1 - Day 21 | 
| Number of patients with abnormal vital signs | Includes supine systolic and diastolic blood pressure, pulse rate, oxygen saturation, body temperature, and respiratory rate | Day 1- Day 21 | 
| Number of participants with abnormal and clinically significant electrocardiogram (ECG) | 12-lead ECG will be taken | Day 1 - Day 21 | 
| Number of participants with abnormal urinalysis | Dipstick test will be performed | Day 1- Day 21 | 
| Number of participants with abnormal coagulation test | Prothrombin time, International normalization ratio, Activated partial thromboplastin time | Day 1- Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum concentration of OC514 in blood plasma | Day 1-Day 4, Day 8, Day 16, Day 17 | 
| Tmax | Time to maximum concentration | Day 1-Day 4, Day 8, Day 16, Day 17 | 
| Cmin | Minimum concentration | Day 1-Day 4, Day 8, Day 16, Day 17 | 
| AUC (0-last) | Area under the time concentration curve from time zero to last measurable concentration | Day 1-Day 4, Day 8, Day 16, Day 17 | 
| AUC (0-inf) | AUC from time zero to infinity | Day 1 and Day 2 | 
| AUC (0-12) | AUC from time zero until 12 hours post dose | Day 3-Day 16 | 
| t1/2 | Elimination half life | Day 1-Day 4, Day 8, Day 16, Day 17 | 
| λz or Kel | Apparent terminal elimination rate | Day 1-Day 4, Day 8, Day 16, Day 17 | 
| CL/F and CL/Fss | Apparent clearance | Day 1-Day 4, Day 8, Day 16, Day 17 | 
| Vz/F and Vz/Fss | Volume of distribution | Day 1-Day 4, Day 8, Day 16, Day 17 | 
| Effect of OC514 administration on QT prolongation | 12-lead ECG will be done | Day 4, Day 8, Day 12, Day 16, Day 17, day 19 |