A Healthy Volunteer Study to Investigate the Blood Concentrations, the Effect on Blood Clotting and the Safety of Multiple Doses of DPOC-4088 Tablets in Different Doses.

NCT01647620 | Terminated Phase 1

• 1 other identifier: DPOC-002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Deep Vein Thrombosis Leg; Stroke (in Patients With Atrial Fibrillation)

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• 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.

• 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.

• The DPOC-4088 plasma concentration vs time profile and Cmax-ss/Cmin-ss following multiple once-daily oral dosing.

• The safety of DPOC-4088 given once-daily for 10 days.

Study Arms (2)

DPOC-4088

ACTIVE COMPARATOR

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

Drug: DPOC-4088

Placebo

PLACEBO COMPARATOR

A 10-day oral dosing of matching placebo prolonged release tablet.

Drug: Placebo

Interventions

DPOC-4088 DRUG

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.

DPOC-4088

Placebo DRUG

A 10-day oral dosing of matching placebo prolonged release tablet.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male between 18 to 50 years of age inclusive.
• Either a non- or a light-smoker (\<5 cigarettes per day) and agrees to refrain from smoking from the evening prior to first dosing until after the last PK sample of each step is drawn.
• Body-mass index (BMI) of 18-32 kg/m2.
• In good health on the basis of history, physical examination, and routine laboratory data.
• Understands the procedures and agrees to participate in the study program by giving written informed consent.
• Coagulation tests including aPTT, ECT, TT and PT within the reference range and a platelet count \>145,000/mm3.
• At screening, normal transaminases and negative Hemoccult Sensa(R) test. In the event of a positive Hemoccult test, the test should be repeated twice. If the results of both repeats tests are negative, the first Hemoccult test result is considered a false positive and the subject may be included.

You may not qualify if:

• Mentally or legally incapacitated, significant emotional problems at the time of the study, or a history of psychiatric disorders within the last 10 years.
• History within the last 10 years of asthma or other pulmonary disease, major cardiovascular, hepatic, endocrine (including diabetes), rheumatological, or renal disease or of prior spine or disc surgery.
• History within the last 10 years of neurologic disease including stroke, transient ischemic attacks, seizure, head trauma, neurological tumors, brain or spinal cord surgery, neuropathy, or neuromuscular illness.
• Active gastrointestinal disease including: peptic ulcer disease, gastritis, clinically significant Helicobacter pylori infection, inflammatory bowel disease, diverticular disease, colonic polyps, or of any gastrointestinal malignancy, or recent (within 3 weeks) benign enteritis.
• History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering study drug to the subject (e.g., surgery within the previous 3 months).
• Donated a unit of blood (450 mL) or participated in another clinical study drug trial within the 4 weeks prior to screening.
• Family or personal history of bleeding disorders, including von Willebrand's disease.
• History of significant gingivitis or other periodontal disease.
• Received any prescription anticoagulant within the 30 days preceding screening including but not limited to warfarin, heparin, low-molecular weight heparin, hirulog, hirudin, argatroban, or dabigatran.
• Has received 14 days prior to first dosing or anticipates needing during the study any prescription or nonprescription (including over the counter) preparation that contains aspirin (including low-dose aspirin), ibuprofen, indomethacin, diclofenac, naproxen, meloxicam, any other NSAID or NSAID-containing product such as pain relievers, cold or sinus remedies, or any other drug which influences platelet aggregation.
• Received any investigational drug within the 30 days preceding screening.
• Regular user of any medication (including over-the-counter medication) for 14 days prior to first dosing, except for acetaminophen. Subject currently uses prescription or nonprescription drugs on a regular basis which cannot be discontinued for 14 days prior to first dosing until the last study visit (including "recreational use" of illicit drugs). Subject has a recent history (within the last 2 years) of drug or alcohol abuse.
• Subjects unable to stop using the following medications during the study (from first dosing until after the last study visit): erythromycin or erythromycin-like drugs, clarithromycin, diltiazem, cimetidine, warfarin-like anticoagulants, cyclosporine, itraconazole (or other systemic antifungal agents in the azole class), nefazodone, selective serotonin reuptake inhibitors (SSRI antidepressants), benzodiazepines, any systemic immunosuppressive agents (including glucocorticoids), cisapride and the H1 antagonists terfenadine and astemizole, and HIV protease inhibitors.
• Unable to refrain from the use of antacids, H2 blockers, sucralfate, or proton pump inhibitors beginning 14 days prior to first dosing until the last study visit.
• Has had major surgery within previous 3 months prior to first dosing or is anticipated to have major surgery within 2 weeks after completion of the study.

Sponsors & Collaborators

• Diakron Pharmaceuticals: lead
• University Ghent: collaborator
• Kinesis Pharma B.V.: collaborator

Study Sites (1)

Drug Research Unit Ghent

Ghent, 9000, Belgium

Location

MeSH Terms

Conditions

Venous Thrombosis; Stroke

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Luc M van Bortel, Prof. Dr.

  University Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2012
• First Posted: July 23, 2012
• Study Start: February 1, 2012
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: February 24, 2015

Record last verified: 2012-07

Locations

BE (1)