A Phase 1 Single-Center Study to Assess Pharmacokinetics, Safety and Tolerability of KT07 in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Low dose KT07
- Conditions
- Healthy Adult Subjects
- Sponsor
- Yiling Pharmaceutical Inc.
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- AUC (Racc_AUCss)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a phase 1 single-center study to assess the pharmacokinetics (PK), safety and tolerability of KT07 capsules in healthy adult subjects. This study consists of 2 parts: Part 1 and Part 2.
The primary objectives of Part 1 include selection of suitable PK markers for bioanalysis, development and validation of GLP bioanalytical methods for follow-up PK studies, assessment of PK of potential markers following an oral administration of KT07, and provision of PK sampling strategy for Part 2.
The primary objective of Part 2 is to evaluate the PK profile following a single dose and multiple doses in healthy adult subjects.
Detailed Description
This is a 2-part PK study. Each Part consists of 3 phases: a 2-week screening phase, drug administration and PK sampling phase, then a safety follow-up visit at Day 7 after the last dose. Subjects enter screening at Visit 1. Part 1: Pilot single-dose PK Study Part 1 is an open-label study. Six (6) eligible male adult healthy volunteers aged between 18 to 65 years will receive a single oral dose of KT07 capsules on Day 1. Part 2: Single and multiple-dose PK Study A total of 20 healthy subjects will participate in this part of the study, which consists of 2 cohorts with 10 subjects each. Subjects will receive either active treatment or placebo treatment in each cohort in a double-blind manner to evaluate PK and safety of KT07.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject voluntarily has agreed to participate in this study and signed an Institutional Review Board (IRB)-approved informed consent before any of the screening procedures will be performed.
- •18 to 65 years of age, inclusive, at screening, male or female.
- •Body mass index (BMI) between 17.5 and 32.0 kg/m2 at screening.
- •Healthy, determined by pre-study medical evaluation and Investigator/designee discretion (medical history, physical examination, vital signs, ECG, and clinical laboratory evaluations).
- •All female subjects of child-bearing potential must have a negative serum pregnancy test result. All female subjects of child-bearing potential and male subjects and their spouse/partner must agree to use a medically acceptable method of contraception (e.g, abstinence, an intrauterine device, a double barrier method such as condom + spermicide or condom + diaphragm with spermicide, a contraceptive implant, an oral contraceptive or have a vasectomized partner with confirmed azoospermia) throughout the entire study period, and for 90 days after study drug discontinuation.
- •Agrees to the collection of nasopharyngeal (NP) swabs for SARS-CoV-2 testing.
Exclusion Criteria
- •Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s) as determined by the Investigator/designee.
- •Any disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs.
- •Any concurrent disease or condition that, in the opinion of the Investigator/designee, would make the subject unsuitable for participation in the clinical study.
- •Subject has history of alcohol and/or illicit drug abuse within one year of the Screening visit.
- •Positive SARS-CoV-2 testing by standard RT-PCR assay.
- •Positive Screening test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, or human immunodeficiency virus (HIV) antibody.
- •Positive urine test for ethanol/drug/cotinine at Screening or Day -
- •History of alcohol abuse as judged by the Investigator within approximately 1 year. Average weekly alcohol intake \> 21 units/week or are unwilling to avoid use of alcohol or alcohol-containing foods, medications or beverages, within 48 hours prior to Day -1 until completion of the study. Positive alcohol test at Screening. (One unit of alcohol equals about 250 mL of beer or lager, 100 mL of wine, or 35 mL of spirits).
- •History of illicit drug abuse, within approximately 1 year or evidence of current use as judged by the Investigator or are unwilling to abstain from illicit drug use consumption during the entire study. Positive drug test, including marijuana.
- •Excessive consumption of coffee, tea, cola, or other caffeinated beverages; excessive consumption is defined as \>6 servings per day (1 serving contains approximately 120 mg caffeine).
Arms & Interventions
Low dose KT07
KT07 single dose (4 capsules) followed by multiple doses for 5 days (tid)
Intervention: Low dose KT07
High dose KT07
KT07 single dose (6 capsules) followed by multiple doses for 5 days (tid)
Intervention: High dose KT07
Low dose placebo
Placebo single dose (4 capsules) followed by multiple doses for 5 days (tid)
Intervention: Low dose Placebo
High dose placebo
Placebo single dose (6 capsules) followed by multiple doses for 5 days (tid)
Intervention: High dose Placebo
Outcomes
Primary Outcomes
AUC (Racc_AUCss)
Time Frame: 13 days
Area under the curve anticipated at plateau
Area under the curve (AUC) 0-t
Time Frame: 13 days
AUC calculation up to the last measurable concentration
Maximum (or peak) serum concentration (Cmax)
Time Frame: 13 days
Assess the peak concentration of KT07
Time to achieve maximum drug concentration (Tmax)
Time Frame: 13 days
Assess when KT07 reach its peak concentration
Trough concentration (Ctrough)
Time Frame: 13 days
Assess the lowest concentration of KT07
Time required to reduce the drug concentration to ½ of its initial value (t1/2)
Time Frame: 13 days
Assess the half-life of KT07
Volume of plasma cleared of drug per unit time (CL/F)
Time Frame: 13 days
Assess the plasma clearance of KT07
AUC0-∞
Time Frame: 13 days
AUC calculation from time 0 to infinity
Volume of distribution at terminal phase (Vz/F)
Time Frame: 13 days
Assess the Volume of distribution of KT07
AUCextrap
Time Frame: 13 days
Percentage of AUCinf-pred due to extrapolation from Tlast to infinity
Cmax (Racc_Cmax)
Time Frame: 13 days
Maximum concentrations anticipated at plateau
Accumulation factor
Time Frame: 13 days
Accumulation factor (R) reflects how much drug is accumulated in the body at steady state after multiple dosing as compared to that after single dosing
Secondary Outcomes
- Causality of adverse events(19 days)
- Severity of adverse events(19 days)
- Incidence of adverse events(19 days)