A study to investigate the concentrations of a new drug DPOC-4088 in blood, and to study the effect of this drug on blood clotting parameters. Furthermore the relation between the blood concentrations and the blood clotting effect will be investigated. Safety will be investigated as well. The objective of these investigations is to determine the optimal dose of DPOC-4088 that, achieves a relevant increase in a specific blood clotting parameter (the ecarin clotting time) without safety concerns.
This is a randomized, double-blind, placebo-controlled, stepwise study of multiple once-daily oral dosing of DPOC-4088 (100 mg in Step 1) in healthy young male subjects. Each Step of the study will include 10 subjects and consist of screening for eligibility followed by a 13-day period during which once-daily oral doses of DPOC-4088 or placebo are administered for 10 consecutive days and blood is sampled for PK/PD measurements.
In each dose step, 8 subjects will receive active drug and 2 subjects will receive matching placebo according to a randomized allocation schedule.
During each Step, DPOC-4088 or placebo will be given each morning on Days 1 through 10, safety permitting. Each of the 10 days of dosing will be preceded by an overnight fast (10 hours). Subjects will have frequent PK/PD sampling performed for a 24 hour period following dosing on Day 1 and for a 72-hour period following dosing on Day 10. On Days 1 and 10, the first meal will be given at 4 hours post-dosing. On other dosing days, subjects will not have breakfast until one hour after dosing. Blood samples will be drawn for PK and PD evaluations immediately prior to dosing and at specified time intervals post-dosing. Following completion of all 10 days of dosing in each Step, subjects will return for a follow-up examination in 1 week (7-9 days).
After completion of all dosing in Step 1, PK, PD and safety data will be analyzed and (if necessary) used to determine the dose for Step 2, the same procedure will be followed for the next dose steps, if necessary.
The safety, tolerability, and the PK profile of DPOC-4088 will be assessed. Additionally, this study will assess the PD profile and the relationship of PK/PD in terms of the ability of DPOC-4088 to inhibit thrombin activity (based on prolongation of aPTT, ECT, TT and PT).
To main objective is to determine the dose of DPOC-4088 that, following multiple once-daily oral dosing, achieves a target increase of 2-fold over baseline in the ecarin clotting time (ECT) at the steady-state trough plasma concentration (Cmin-ss) without safety concerns.
Trial Stopped: Diakron Pharmaceuticals couldn't fulfill the financial responsibility of the study
- Placebo Biological
Intervention Desc: A 10-day oral dosing of matching placebo prolonged release tablet. ARM 1: Kind: Experimental Label: Placebo Description: A 10-day oral dosing of matching placebo prolonged release tablet.
- DPOC-4088 Drug
Intervention Desc: A 10-day oral dosing of DPOC-4088 prolonged release tablet (20 hr release formulation). Starting dose in dose step 1 is 100 mg daily. ARM 1: Kind: Experimental Label: DPOC-4088 Description: A 10-day oral dosing of DPOC-4088 prolonged release tablet (20 hr release formulation). Starting dose in dose step 1 is 100 mg daily
- Allocation: Randomized
- Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
- Purpose: Treatment
- Endpoint: Pharmacokinetics/Dynamics Study
|Type||Measure||Time Frame||Safety Issue|
|Primary||The dose of DPOC-4088 that, following multiple once-daily oral dosing, achieves a target increase of 2-fold over baseline in the ecarin clotting time (ECT) at the steady-state trough plasma concentration (Cmin-ss) without safety concerns||No|
|Secondary||The dose of DPOC-4088 that, following multiple once-daily oral dosing, achieves a target increase of 1.5-fold over baseline in the activated partial thromboplastin time (aPTT) at Cmin-ss without safety concerns.||No|
|Secondary||The extent and duration (at the end of dosing) of inhibition of coagulation parameters as measured by the change from baseline in ECT and aPTT.||No|
|Secondary||The DPOC-4088 plasma concentration vs time profile and Cmax-ss/Cmin-ss following multiple once-daily oral dosing.||No|
|Secondary||The safety of DPOC-4088 given once-daily for 10 days.||Yes|