A Study of Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of VE-01902 in Healthy Volunteers
- Conditions
- Atrial FibrillationCardiovascular - Coronary heart disease
- Registration Number
- ACTRN12618001509257
- Lead Sponsor
- VCR1
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 134
1. Male or female aged 18 to 55 years, inclusive;
2. Body mass index (BMI) between 19 and 33 kg/m2 inclusive, with a minimum weight of 50 kg;
3. Healthy as determined by pre-study medical history, physical examination, vital signs,
complete neurological examination and 12-lead electrocardiogram (ECG) confirming normal sinus rhythm;
4. Negative tests for Hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV)
and human immunodeficiency virus (HIV)-1and HIV-2 antibody at screening;
5. Routine laboratory screening tests as specified below should be within normal limits or any abnormalities should be not clinically significant, as determined by the investigator at screening and day -1; however, results of the coagulation panel, platelet count and hemoglobin should be within normal limits, and liver function tests (specifically, total bilirubin, ALT and AST) should not exceed 1.5x the upper limit of normal;
6. Negative screen for alcohol and drugs of abuse at screening and admission;
7. Non-smokers or casual smoker who uses no more than 10 cigarettes (or equivalent quantity of any other nicotine containing products e.g. cigars, chewing tobacco, snuff, vaping, e-cigarettes, and etc.) per week. Subject must abstain from smoking 5 days prior to admission and throughout the entire study period, and test negative on Day -1 for urine cotinine test. ;
Female participants:
8. Must be of non-child-bearing potential by surgical sterilization or postmenopausal (no menses for the previous 12 months without alternative medical cause and confirmed by FSH testing),
OR
9. Must not be pregnant, breast feeding, or planning to become pregnant AND must be practicing both a highly effective method of birth control for at least 30 days after the last dose of study drug and a barrier method (such as condom use). Highly-effective methods of birth control include: hormonal contraception (e.g. birth control pill, injection, implant, transdermal patch or vaginal ring), an intrauterine device, tubal ligation or a sole partner with a vasectomy. Progestin-based contraception that suppresses ovulation (e.g. Depo-Provera) is allowed. Estrogen-containing contraceptives that provide suppression of ovulation may be allowed. However, high-dose estrogen (greater than 35 microgram ethinyloestradiol)-containing contraceptives are not allowed in this study. Gonadotropin-releasing hormone agonist contraceptives are not allowed in this study. Abstinence from penile-vaginal intercourse for the above duration is acceptable, if it is consistent with the usual and preferred lifestyle of the participant;
10. Negative serum pregnancy test at screening and negative urine pregnancy test on admission of each treatment period (women of childbearing potential only);
Male participants:
11. Must be practicing a highly effective method of birth control with female partners of
childbearing potential from screening throughout the study and for at least 90 days after the last investigational drug administration. Highly effective birth control methods are as described above and include vasectomy, or condom use in combination with partner’s use of highly effective contraception
If any of the following exclusion criteria apply, the volunteer must not enter/continue in the study:
1.Aspirin or Non-steroidal anti-inflammatory drug (with the exception of acetaminophen) use in the preceding 2 weeks.
2.Have used any anticoagulants independent of participating in a clinical trial, or if anticoagulant use was due to participation in a clinical trial then washout period should be maximum of the longer period of either 5x PK t1/2 or PD t1/2
3.Have any significant hematologic past medical history of hypercoagulable or bleeding disorders, unexplained bleeding, bruising, hemorrhage, blood clots, or thromboembolism as determined by the PI;
4.Have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders;
5.Have a clinically relevant surgical history (surgery within the last 2 months, planned surgery within the following month);
6.Have a history of hyperemesis, Crohn’s, Inflammatory Bowel Disease, Irritable Bowel Syndrome, hematuria, melena, hematochezia;
7.Have a history of severe drug allergy or hypersensitivity or food allergy, including anaphylaxis;
8.Have a history of alcoholism or drug abuse;
9.Consume more than 14 units of alcohol a week (1 unit of EtOH = 1 glass (25 cl) of beer with 3% of alcohol = 7.5 g, or 1 glass (25 cl) of beer with 6% of alcohol = 15 g, or 1 glass (12.5 cl) of wine with 10% of alcohol = 12 g, or 1 glass (4cl) of aperitif with 42% of alcohol = 17 g] on history, or exhibit detectable alcohol levels by breathalyzer;
10.Have a significant infection or known inflammatory process on screening or admission (ie. infection, autoimmune disease, immunosuppression regimen);
11.Have acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, heartburn) at the time of screening or admission;
12.Have used any prescription medicines, over the counter medicines, or herbal supplements, within two weeks of admission, with the exception of acetaminophen or approved method of hormonal contraception;
13.Have used any investigational drug or participated in any clinical trial within 90 days prior (or if longer, 5 times the half life of the investigational product) to screening;
14.Have participated in more than 1 clinical trial within the 3 months prior to screening;
15.Have donated or received any blood or blood products within the 3 months prior to screening;
16.Have medical dietary restrictions that cannot be accommodated by the clinical unit;
17.Are an employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child, whether biological or legally adopted.
18.Cannot communicate reliably with the investigator;
19.Are unlikely to co-operate with the requirements, including duration of admission to the study and expected follow up visit;
20.Are unwilling or unable to give written informed consent.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Assess the safety and tolerability to VE-01902[Look for AEs (especially Clinically Evident Bleeding) 7 days post dose for patients receiving a single dose, 14 days post dose for patients receiving 7 days of dosing, or 11 days post dose for patients receiving 5 days of dosing];Assess composite hemostatic activity of VE-01902 via hematology (platelet count) and coagulation screens (PT, aPTT, INR).[Screen patient blood on hematology and coagulation screens SAD (pre-dose, day 2, day 4, day 7) MAD 1 (pre-dose, day 1, day 2, day 3, day 5, day 7, day 10, and day 13) MAD 2-5 ((pre-dose, day 2, day 3, day 8, and day 11)]
- Secondary Outcome Measures
Name Time Method Assess effect on pharmacodynamics of VE-01902[Analysis of blood (at pre-dose 1h, 2h, 3h, 4h, 6h, 8h, and 24h) via the Thrombin Generation Assay, Analysis of blood (at pre-dose, 2h, 3h) via the Direct Thrombin Inhibition Analysis of blood (at predose, 2h, 3h, 4h, and 6h) via the P-selectin flow cytometry for platelet biomarkers];Assess pharmacokinetic profile of VE-01902, parameters: AUC, Cmax, Tmax, dose proportionality, accumulation, time dependence, steady state, food effect.[Bioanalysis of blood (pre-dose, and at 30m, 1h, 2h, 3h, 4h, 6h, 8h, 12h, and 24h post-dose) via liquid chromatography mass spec system. For the MAD 1 this analysis will occur on day 7 as well as day 1, for SAD just on day 1. For MAD 2-5 this analysis will occur on day 5 as well as day 1,]