Safety and Pharmacokinetics Study of CPL500036 Compound in Healthy Volunteers

Study Overview
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Brief Summary
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The planned study is to determine the safety and pharmacokinetic properties of CPL500036 compound after single and multiple (two weeks) administration in healthy volunteers.

Detailed Description
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This is to be one-centre, single ascending dose and double-blind multiple ascending dose two part study of CPL500036 compound in healthy volunteers. PART A is a single dose, open-label part with CPL500036 compound administered with dose escalation between cohorts. PART B is a multiple, double-blind part with CPL500036 compound administered for 14 days with dose escalation between cohorts. Participants in this part are to be randomized to receive Investigational Medicinal Product (IMP) or placebo in 3:1 ratio. Safety and pharmacokinetic properties of CPL500036 compound is to be determined following different doses in single oral IMP administration in PART A and different doses of IMP administered orally for two weeks in PART B.

Official Title
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One Centre Single Ascending Dose and Double Blind Multiple Ascending Dose, Safety and Pharmacokinetics Phase I Study of CPL500036 Compound in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: CPL500036 compound
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasian female or male, Age: 18-55 years old, inclusive, Body-mass index (BMI): ≥18.5 kg/m^2 and <29.9 kg/m^2, Non-smoker and nonuser of tobacco products for at least 3 months before screening, Physical examination without any clinically relevant abnormality, Laboratory values not clinically significant, Volunteer (or his/her partner) of childbearing potential willingness to use acceptable forms of contraception. Exclusion Criteria: Known allergy or hypersensitivity to other drugs similar in structure or class to CPL500036 compound, or to any excipients of the formulation, Any known significant current or past acute or chronic disease or condition, Participation in other clinical trial within 90 days preceding the screening, Blood drawn within 30 days prior to inclusion to the study (more or equal to 300mL), Positive results from pregnancy test for female participants, Lactation in women participants, Hypotension or hypertension in medical history, Long QT interval syndrome or is under the treatment with antiarrhythmic drugs, Narcotic, alcohol addiction or abuse, Participant who adhere to a special diet (e.g. low calories, vegetarian).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPL500036<br>PART A: 7 cohorts are to receive single dose of IMP. Each participant is to take single dose of IMP. There is to be dose escalation between cohorts. PART B: 4 cohorts are to receive multiple dose of IMP. Each participant is to take IMP once daily for 14 days. There is to be dose escalation between cohorts. | Drug: CPL500036 compound<br>* IMP is a capsule with CPL500036 as an Active Pharmaceutical Ingredient (API).<br>|
| Placebo Comparator: Placebo<br>PART B: 2 Participants from 4 cohorts (total of 8 people) are to receive masking placebo capsules once daily for 14 days. There is to be dose escalation between cohorts. Participants are to be randomized within cohorts. | Drug: Placebo<br>* matching placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of maximum tolerated dose (MTD) or administration of the maximum dose provided in the protocol after single and multiple oral administration of IMP. | MTD is defined as the highest dose for which no more than 1 of the 6 treated volunteers (less than 1/3) exhibits dose limiting toxicity (DLT). | up to 24 hours after single administration of IMP in PART A and up to 24 hours after the last IMP administration in PART B | 
| Safety and tolerability of IMP after single and multiple oral administration based on laboratory values, vital signs, ECG, physical examinations and Adverse Events monitoring. | Participants are to be closely observed to assure maximal safety and to collect occurrence of all adverse events. All participants are to be monitored for clinically relevant changes in physical examination, vital signs, 12-lead ECG assessment and deviations from normal in clinical laboratory results (complete blood count, blood chemistry, urinalysis). To follow-up on all study participants telephone calls with a request for information regarding their health condition are to be made. | up to 14 days in PART A and up to 28 days in PART B of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - maximum CPL500036 plasma concentration | The maximum concentration of the CPL500036 compound in plasma after IMP administration, obtained directly from the measured concentrations. | up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B | 
| AUC(0-72) - area under the plasma concentration - time curve from time 0 to 72h after IMP administration for CPL500036 | The AUC(0-72) is a measure of total plasma exposure to the drug from time point zero to 72 hours after IMP administration. | up to 72 hours after administration of IMP in PART A | 
| AUC(0-24) - area under the plasma concentration - time curve from time 0 to 24h after IMP administration for CPL500036 | The AUC(0-24) is a measure of total plasma exposure to the drug from time point zero to 24 hours after IMP administration. | up to 24 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 and 14 in PART B | 
| AUC(0-inf) - area under the plasma concentration - time curve from time 0 to infinity time for CPL500036 | The AUC(0-inf) is a measure of total plasma exposure to the drug from time point zero extrapolated to infinity. | up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B | 
| Tmax - time to reach maximum CPL500036 concentration | The Tmax is time to reach the maximum plasma concentration (Cmax), obtained directly from the actual sampling times. | up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B | 
| Kel - terminal elimination rate constant | Kel is to be estimated via linear regression of time versus log of concentration. | up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B | 
| T1/2 - The plasma elimination half-life for CPL500036 compound | T1/2 is to be calculated as 0.693/Kel. | up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B | 
| C (1,t) - CPL500036 concentration | The concentration of CPL500036 on day t before product administration. | Determined on Day 2, 3, 4, 5, 6, 8, 9, 10, 11, 12 and 13 in PART B. | 
| C (Tmax, t) - CPL500036 concentration | The concentration on day t measured on time Tmax which was calculated in PART A of the study. | Determined on Day 2, 3, 4, 5, 6, 8, 9, 10, 11, 12 and 13 in PART B. | 
| Amount of CPL500036 in each urine collection sample | It is to be calculated as CPL500036 concentration in urine sample times volume of urine collection. | up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B | 
| Ae - total amount of CPL500036 excreted in urine | Ae is to be calculated as asymptote of the plot of the cumulative amount of drug excreted after each collection interval plotted against the median of the collection interval. | up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B | 
| Clr - renal clearance | Clr is to be calculated by linear least squares regression analysis on semi-logarithmic transformed data (CLr = excretion rate/C). | up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B | 
| Excretion rate | Excretion rate calculated as = CLr/V x Dose x exp(-kt) | up to 72 hours after administration of IMP in PART A and up to 24 hours after the IMP administration determined on Day 1, 7 in PART B and up to 72 hours after the last IMP administration on Day 14 in PART B |