Double-blind, Randomized, Placebo-controlled, Phase I Clinical Study of the Safety, Tolerability and Pharmacokinetics of Ascending Doses of X243 After Single and Multiple Oral Administration in Healthy Volunteers.
Overview
- Phase
- Phase 1
- Intervention
- XC243 50 mg single
- Conditions
- Healthy Volunteers
- Sponsor
- PHARMENTERPRISES LLC
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- Number of Adverse events (AEs) per treatment arm
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
A double-blind, randomized, placebo-controlled, Phase I clinical study of the safety, tolerability and pharmacokinetics (PK) of ascending doses of XC243 after single and multiple oral administration in healthy volunteers. It's planned to include sequentially 2 cohorts of 7 volunteers who will receive a single dose of XC243 (50 mg and 100 mg) or placebo (cohort ratio 5:2), 1 cohort of 14 volunteers who will receive a single dose of XC243 200 mg or placebo first on an empty stomach, and after the washing period after eating (cohort ratio 12:2) and 1 cohort of 10 volunteers who will receive XC243 200 mg or placebo on an empty stomach during 14 days (cohort ratio 8:2).
Detailed Description
The study will be conducted in 1 centre. The study will consist of 3 parts: single-dose ascending study, single-dose food effect study for dose 200 mg, repeated dose study of 200 mg over 14 days. The volunteers of single dosing cohorts will receive the investigated drug (ID) ХС243 or placebo once and stay at the study center for at least 24 hours after the ID administration to monitor the safety parameters and for sampling for PK analysis. The Follow-up will last 7 days, during which safety parameters and PK in volunteers will be studied. Based on all safety data from the XC243 50 mg cohort, the Data Safety Monitoring Committee (DSMC) will consider dose increase and entry of the 100 mg cohort. If the single dose of ХС243 100 mg is considered to be safe, the third dosing cohort of 200 mg will be included in the single-dose food effect study. The volunteers of third dosing cohort will receive the ID ХС243 (200 mg) or placebo once on an empty stomach.The Follow-up will last 7 days, during which safety parameters and PK in volunteers will be studied. The washing period will last 7 days, after which volunteers will receive the ID ХС243 (200 mg) or placebo once after eating. The Follow-up will last 7 days too. If the single dose of ХС243 200 mg is considered to be safe, the fourth multiple dosing cohort of repeated dose of 200 mg will be included. The volunteers from multiple dosing cohort will receive the ID (ХС243 or placebo) once a day during 14 days and will stay at the hospital (study center) within 15 days. The Follow-up will last 14 days, during which they will study safety parameters and PK in volunteers.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The volunteer read, understood and signed the Information Leaflet and the Informed Consent Form to participate in the study;
- •Non-smoking men (nonsmokers at least within the last year before the screening) at the ages from 18 through 45;
- •Verified diagnosis "healthy" according to standard clinical, laboratory and instrumental methods of examination;
- •Blood Pressure (BP): Systolic blood pressure (SBP) 100 to 130 mm Hg, diastolic blood pressure (DBP) from 70 to 89 mm Hg (inclusive);
- •Heart rate (HR) from 60 to 90 units/min (inclusive);
- •Respiratory rate (RR) from 12 to 20 min-1 (inclusive);
- •Body temperature from 36 to 36.9 ° C (inclusive);
- •Body mass index from 18.5 to 30.0 kg/m2 with body weight of more than 45 kg and no more than 110 kg;
- •Negative result of breath alcohol test, urine test for narcotic substances;
- •Consent to use adequate contraceptive methods throughout the study, including the post-observation period (7 days in Cohorts 1-3 and 14 days in Cohort 4), as well as 90 days at its end;
Exclusion Criteria
- •The history of chronic diseases of the cardiovascular, bronchopulmonary, nervous, endocrine, musculoskeletal system, as well as the gastrointestinal tract (GI), liver, kidneys, blood, mental illness, epilepsy or seizure;
- •Deviations of standard laboratory and instrumental values, as well as physical examination results from normal values at screening;
- •History of GI surgery (excluding appendectomy);
- •Administration of drugs less than 2 weeks before screening (including preparations of plant origin, vitamins and dietary supplements), with the exception of episodic administration of paracetamol at a dose of up to 1.5 g/day;
- •Taking drugs that affect liver function (for example, inhibitors and/or inducers of cytochrome P450) less than 30 days before screening;
- •Presence of antibodies to HIV and hepatitis C virus at screening, presence of hepatitis B virus surface antigen, presence of antibodies to T. Pallidum \*;
- •Presence of a positive test for SARS-CoV-2 at screening;
- •Presence of unstable sleep structure (for example, night shift work, sleep disturbances, insomnia, recent return from another time zone, etc.), extreme physical activity (for example, lifting weights);
- •A special diet (for example, vegetarian, vegan, hypocaloric (less than 1000 kcal/day));
- •Taking alcohol within 4 days of screening or testing positive for exhaled alcohol at screening or on Day -1;
Arms & Interventions
XC243 50 mg single
Cohort 1 - 7 subjects will be randomized in a 5:2 ratio to be treated either XC243 50 mg (5 subjects) or placebo (2 subjects, see placebo single arm)
Intervention: XC243 50 mg single
XC243 100 mg single
Cohort 2 - 7 subjects will be randomized in a 5:2 ratio to be treated either XC243 100 mg (5 subjects) or placebo (2 subjects, see placebo single arm)
Intervention: XC243 100 mg single
Placebo single
Placebo comparator arm will consist of 4 subjects (1 subject each from Сohorts 1 and 2)
Intervention: Placebo single
XC243 200 mg single-dose food effect
Cohort 3 - 14 subjects will be randomized in a 12:2 ratio to be treated either XC243 200 mg (12 subjects) or placebo (2 subjects, see placebo single arm) first on an empty stomach, and after the washing period after eating
Intervention: XC243 200 mg single-dose food effect
Placebo single-dose food effect
Placebo comparator arm will consist of 2 subjects from Cohort 3
Intervention: Placebo single-dose food effect
XC243 200 mg multiple
Cohort 4 - 10 subjects will be randomized in a 8:2 ratio to be treated either XC243 200 mg (8 subjects) or placebo (2 subjects, see placebo multiple arm)
Intervention: XC243 200 mg multiple
Placebo multiple
Placebo comparator arm will consist of 2 subjects from cohort 4
Intervention: Placebo multiple
Outcomes
Primary Outcomes
Number of Adverse events (AEs) per treatment arm
Time Frame: Day 1-Day 35
Adverse events will be classified according to CTCAE. Adverse events will be summarized descriptively by treatment arm. Verbatim terms will be mapped to preferred terms and organ systems using the current Medical Dictionary for Regulatory Activities version.
Secondary Outcomes
- Pharmacokinetics of XC243 by assessing AUC0-inf(Day 1- Day 14)
- Pharmacokinetics of XC243 by assessing Cmax(Day 1- Day 14)
- Pharmacokinetics of XC243 by assessing Tmax(Day 1- Day 14)
- Pharmacokinetics of XC243 by assessing T1/2(Day 1- Day 14)
- Pharmacokinetics of XC243 by assessing AUC0-t(Day 1- Day 14)