A Phase I Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Trial in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ICP-022 Following Single and Multiple Escalating Dose
Overview
- Phase
- Phase 1
- Intervention
- ICP-022
- Conditions
- Systemic Lupus Erythematosus
- Sponsor
- Innocare Pharma Australia Pty Ltd
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- Number of participants with treatment-related adverse events
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a single center, randomized, double-blind, placebo-controlled, dose escalation study in healthy subjects to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ICP-022 following oral single and multiple escalating dose administration.
Detailed Description
This is a single center, randomized, double-blind, dose escalation, placebo-controlled, first-in-humans phase 1 study to investigate the safety and tolerability of single and multiple escalating doses of ICP-022 in healthy volunteers. 40 healthy male participants (aged between 18 and 55 years of age inclusive) will be enrolled into Part 1 (single escalating dose administration) of this study, and additional 24 male subjects will be enrolled in Part 2 (multiple escalating dose administration). Part 1a consists of 5 cohorts of 8 participants each, while Part 2 includes 3 cohorts of 8 participants each. Part 1a consists a treatment period with single oral dosing, and a safety follow-up to 7 days after dosing. Cohort 4 of Part 1a will return on Day 8 to repeat the study under fed condition in Part 1b. Part 2 consists a treatment period with multiple dosing (once per day for 14 consecutive days), and a safety follow-up until 28 days after dosing. All subjects will receive either ICP-022 or placebo.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male subjects age ≥18 and ≤55 years
- •Body mass index ≥19 and ≤31 kg/m2, with minimum body weight of 50kg
- •No clinically significant findings in the medical history and physical examination, especially with regard to the respiratory, heart, immune system, pancreas, liver, bile and gastrointestinal systems
- •No clinically significant laboratory values and urinalysis, unless the investigator considers any abnormality to be clinically irrelevant;
- •Subjects with a partner of child-bearing potential must be willing to use an approved form of contraception with a failure rate of \<1%. Subjects must be willing to use a condom during sexual intercourse whether or not their partner is of child-bearing potential from screening until 90 days after their final study visit.
- •Normal electrocardiogram (ECG), blood pressure, and heart rate, unless the investigator considers any abnormality to be clinically irrelevant
- •Informed consent must be obtained in writing for all subjects personally at enrollment
Exclusion Criteria
- •Subjects with medically important events
- •Having 1st degree relative with coronary heart disease at age \<60
- •Using of prescription drugs including but not limited to those known to interfere with metabolism of drugs within 30 days prior to dosing
- •Exposure to any other medication, including over-the-counter medications, herbal remedies and vitamins for at least 14 days before randomization (except paracetamol
- •Participation in another study with any investigational drug in 30 days or five half-lives (whichever is longer) preceding the study
- •Current smoker, defined as more than 10 cigarettes or equivalent per day before the beginning of the study (participants currently smoking ≤10 cigarettes daily and able to completely stop smoking during the study from screening until follow-up are eligible)
- •Symptoms of a clinically significant illness in the 3 months before the study
- •Presence or sequelae of respiratory, gastrointestinal, immune system, heart, liver or kidney disease, including asymptomatic unconjugated hyperbilirubinemia or asthma, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
- •Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease
- •Hemorrhoids or anal diseases with regular or recent presence of blood in feces
Arms & Interventions
ICP-022
There are 5 cohorts in the Part 1 phase of the trial. Three quarters of subjects will be randomized to receive ICP-022 in a double-blind fashion. Five dose levels will be evaluated; dose escalation steps may be modified based on the safety from the previous dose. Cohort 4 will return on Day 8 and receive a single dose of ICP-022 under fed conditions. In Part 2 phase of the trial,three quarters of subjects will be randomized to receive the ICP-022 in a double-blind fashion in 3 cohorts. ICP-022 will be administered once a day for 14 consecutive days.
Intervention: ICP-022
Placebos
In part 1 phase of the trial, one quarter of subjects will be randomized to receive placebo in a double-blind fashion. Cohort 4 will return on Day 8 and receive a single dose of placebo under fed conditions. In Part 2 phase of the trial,one quarter of subjects will be randomized to receive placebo in a double-blind fashion. Placebo will be administered once a day for 14 consecutive days.
Intervention: Placebos
Outcomes
Primary Outcomes
Number of participants with treatment-related adverse events
Time Frame: up to 28 days
Number of participants with treatment-related adverse events will be collected and the percentage of AE of different grades will be assessed.
Secondary Outcomes
- Maximum plasma drug concentrations (Cmax)(up to 16 days)
- Area under the concentration time curve up to the last data point above LOQ (AUC(last))(up to 16 days)
- Time of maximum plasma drug concentrations (Tmax)(up to 16 days)
- Area under the concentration time curve up to the time "t" (AUC(0-t))(up to 16 days)
- Apparent half-life for designated elimination phases (t½)(up to 16 days)
- Percent target occupancy(up to 16 days)