Careseng 1370 for Healthy Volunteers

Phase 1

Terminated

Conditions: Chemotherapy-induced Myelosuppression

Interventions: Drug: Careseng 1370

Registration Number: NCT03974516

Lead Sponsor: i Cure Biotech Co., Ltd.

Brief Summary: This study will be performed in healthy volunteers in a conventional 3+3 dose-escalation design.

Detailed Description: Four cohorts (dose level A, B, C, and D) of up to 6 evaluable volunteers per cohort are planned to be sequentially accrued to receive Careseng 1370 1, 2, and 3 sachets per day, 4,000 mg/sachet before meal (starting from 1 sachet). At least 5 days of staggering and with the investigator's judgement of no safety concern will be required to administer the next volunteer for the first three volunteers of each cohort. The staggering time is counted from Day 1 of one volunteer to Day 1 of the next volunteer.

Careseng 1370 should be taken around 1 hour before meal. No volunteer is allowed to be assigned to more than 1 dose level. All dose escalation/de-escalation decisions will be made by the Data and Safety Monitoring Board (DSMB).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 13

Inclusion Criteria

Adult aged between 20-40 years old (inclusive)
Physically and mentally healthy volunteer as confirmed by an interview, medical history, clinical examination, chest X-rays, and electrocardiogram. Volunteer with non-clinically significant signs or symptoms may be eligible at investigator's discretion.
Body Mass Index (BMI) between 18.5 and 24, inclusive (BMI will be calculated as weight in kilogram [kg]/(height in meters)2 [m2])
Clinically normal hematology, biochemistry and urinalysis determinations based on investigator's discretion. Volunteer with non-clinically significant signs or symptoms may be eligible at investigator's discretion.
Volunteer is willing and able to comply with study procedures and sign informed consent prior to initiation of any study-mandated procedures.

Exclusion Criteria

Volunteer who has a history or evidence of a medical condition that would expose them to a risk of a significant adverse event or interfere with the assessments of safety or pharmacodynamics variables during the course of the trial, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, immune, neurological, musculoskeletal or hematological disease as determined by the clinical judgment of the investigator
Volunteer has received any other investigational agent within 28 days prior to the first dose of study drug
Volunteer has taken or potentially takes any herbal medication/supplements/medicinal food, prescription medication and/or over-the-counter medication within 2 weeks prior to the first dose of study drug
Volunteer has alcohol, caffeine, grapefruit juice, or nicotine consumption within 24 hours prior to the first dose of study drug
Female volunteer of childbearing potential who:
- is lactating; or
- has positive pregnancy test result at eligibility checking; or
- refuses to adopt at least two forms of birth control (at least one of which must be a barrier method) from Screening visit to Final visit.
Note:

Acceptable forms include:
1. Established use of oral, injected or implanted hormonal methods of contraception.
2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).
3. Barrier methods of contraception: Condom OR Occlusive cap (diaphragm or cervical/vault caps)
Male volunteer with female spouse/partners who are of childbearing potential refuses to adopt at least two forms of birth control (at least one of which must be a barrier method) from Screening visit until Final visit
Known or suspected allergy or hypersensitivity to any ingredients of study product
With history of stroke, myocardial infarction, or Coronary Artery Bypass Graft (CABG) surgery within the last 6 months prior to the screening visit
With history of cardiac failure (NYHA class 2 or above), unstable angina, or life-threatening arrhythmia within the last 6 months prior to the screening visit Note: NYHA = New York Heart Association
With blood pressures as systolic blood pressure < 90 mmHg or > 170 mmHg or diastolic blood pressure < 50 mmHg or > 120 mmHg at eligibility checking
History of psychiatric disorder
History of left ventricular outflow obstruction, such as aortic stenosis and hypertrophic cardiomyopathy
With a history of human immunodeficiency virus (HIV) infection or hepatitis B or C infection
Plan to receive surgery from Screening visit until Final visit
Known or suspected hypersensitivity to any component of Careseng 1370, including components in plants of genus Panax, Tween 80, Kolliphor® P188, Fujicalin, and ginseng flavor

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Careseng 1370 Level A	Careseng 1370	Level A (1 sachet): 1 sachet before breakfast. Careseng 1370 granule 4,000 mg sachet consisted of 652 mg (16.3%, w/w) DS-1370 drug substance powder (dry extracts of Panax notoginseng stems and leaves)
Careseng 1370 Level B	Careseng 1370	Level B (2 sachets): 1 sachet before breakfast, 1 sachet before lunch. Careseng 1370 granule 4,000 mg sachet consisted of 652 mg (16.3%, w/w) DS-1370 drug substance powder (dry extracts of Panax notoginseng stems and leaves)
Careseng 1370 Level C	Careseng 1370	Level C (3 sachets): 1 sachet before breakfast, 2 sachets before lunch. Careseng 1370 granule 4,000 mg sachet consisted of 652 mg (16.3%, w/w) DS-1370 drug substance powder (dry extracts of Panax notoginseng stems and leaves)
Careseng 1370 Level D	Careseng 1370	Level D (1 sachet)(modified cohort): 1 sachet before breakfast on 1st, 3rd and 5th days. Careseng 1370 granule 4,000 mg sachet consisted of 652 mg (16.3%, w/w) DS-1370 drug substance powder (dry extracts of Panax notoginseng stems and leaves)

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs) and/or Serious Adverse Events (SAEs)	Day -14 to Day 22	An AE is any untoward medical occurrence in a volunteer or clinical investigation participant administered a study medication and that does not necessarily have a causal relationship with this treatment. Laboratory abnormalities should not be recorded as AE unless determined to be clinically significant by Investigator. A SAE is defined as an AE meeting one of the following conditions: * Death during the period of protocol defined surveillance * Life Threatening Event (defined as a participant at immediate risk of death at the time of the event) * An event requiring in volunteer hospitalization or prolongation of existing hospitalization during the period of protocol defined surveillance * Results in congenital anomaly or birth defect * Results in a persistent or significant disability/incapacity * Based upon appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With no Change From Baseline to Applicable Post-dosing Visits in Body Weight (kg)	Day -14 to Day 22	\*Baseline will be the value of measurement closest to and before start of IP administration. "Body weight unchanged from Baseline to Day X" indicates that the body weight on Day X minus the body weight at baseline has a 95% confidence interval that includes zero.
Number of Participants With Clinical Laboratory Abnormalities	Day -14 to Day 22	The laboratory examinations include Hematology tests (CBC, PT and aPTT), Biochemistry (AST, ALP, ALT, bilirubin, creatinine, BUN, CRP, total protein, r-GT, lipid and electrolytes) and Urinalysis (pH, protein, RBC, WBC and urine cast). \*Baseline will be the value of measurement closest to and before start of IP administration.
Number of Participants With Vital Signs Abnormalities	Day -14 to Day 22	Vital signs measurement will consist of systolic/diastolic blood pressure, respiratory rate, pulse rate or heart rate, and body temperature.
Number of Participants With Physical Examination Abnormalities	Day -14 to Day 22	Physical examination will include the following items: general appearance, skin, eyes, ears, nose, throat, head and neck, heart, chest and lungs, abdomen, extremities, lymph nodes, musculoskeletal, neurological and others.
Plasma Concentration of Marker Ingredients in Careseng 1370, 20(S)-Protopanaxadiol (PPD) and Its Metabolites	Day 2 to Day 8	Maximum plasma concentration (Cmax) of PPD and its metabolites, M-C1, and M-C2.
Participants With Abnormal Sinus Rhythm	Day -14 to Day 22	Sinus rhythm was measured by 12-lead EKG
Significantly Abnormal Ventricular Rate Compared to Baseline	Day -14 to Day 22	Ventricular rate was measured by EKG.
Significantly Abnormal PR, QRS, QT, QTc Intervals Compared to Baseline	Day -14 to Day 22	PR, QRS, QT and QTc intervals were measured by EKG.