Anticoagulant reversal therapy Other
Conditions
Interventions
This healthy volunteer study will evaluate the efficacy and safety of a single intravenous (IV, administered via injection into a vein) dose of the test medicine for reversal of anticoagulation (blood
Sponsors
Norgine (United Kingdom)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Must provide written informed consent 2. Must be willing and able to communicate and participate in the whole study 3. 18 to 55 years inclusive at the time of signing informed consent 4. Must agree to adhere to the contraception requirements defined in the clinical protocol 5. Healthy males or non-pregnant, non-lactating healthy females of non-childbearing potential (WONCBP) or non-pregnant, non-lactating healthy females on low-user-dependency progesterone-only contraception (e.g., injected, subdermal, intrauterine) who will not be menstruating at the time of study treatment. A woman is considered to be of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or is postmenopausal (has had no menses for 12 months without an alternative medical cause and a serum follicle-stimulating hormone [FSH] concentration =40 IU/L. 6. Have suitable veins for multiple venepunctures/cannulation and IV infusions as assessed by the investigator or delegate at screening 7. Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening 8. Weight >60 kg at screening 9. WBCT = the upper limit of normal (295 secs) at screening and admission prior to the first NIMP dose
Exclusion criteria
Exclusion criteria: 1. Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients 2. Known allergy to edoxaban, apixaban, rivaroxaban or ciraparantag 3. Any contraindication to the use of the anticoagulant drugs (edoxaban, apixaban, or rivaroxaban) as per the Summary of Product Characteristics for each product 4. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator; hay fever is allowed unless it is active 5. History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or GI disease, neurological or psychiatric disorder, as judged by the investigator 6. Subjects with a personal or family history of clotting disorder or haematologic abnormality, such as excessive bleeding, joint haematoma, thrombovascular disease, thrombocytopenia, or any chronic condition requiring treatment with transfusions 7. Subjects with a history of a significant head injury in the last 2 years 8. Subjects with a history of venous thromboembolic episodes (including deep vein thrombosis and pulmonary embolism) 9. Subjects with a history of unexplained syncope within 6 months prior to screening 10. Subjects with a history of major bleeding, trauma, surgical procedure of any type, or vaginal delivery within 6 months prior to screening 11. Presence or history of peptic ulcer or GI bleeding (including hematemesis, melena, or rectal bleeding) within 6 months prior to screening. 12. Presence or history of minor bleeding episodes (e.g., epistaxis, unexplained bruising or gingival bleeding) within 6 months prior to screening, or a long-standing history of such bleeding. 13. Dental extraction or surgery in the 4 weeks prior to admission or planned during the study until after the follow-up visit. 14. Female subjects only: history of excessive or dysfunctional uterine bleeding (unless the subject had a subsequent hysterectomy).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Results of the formal statistical analysis of the proportion of subjects who achieve a WBCT = the upper limit of normal (295 secs) within 1 h after administration of ciraparantag/placebo, which is subsequently sustained after 1 h through to at least 6 h after ciraparantag/placebo dosing measured using Perosphere Technologies’ Point-of-Care (PoC) Coagulometer at Screening until the follow-up visit (up to 6 days post-discharge) | — |
Secondary
| Measure | Time frame |
|---|---|
| Statistical analysis of the proportion of subjects who achieve WBCT = the upper limit of normal (295 secs) within 30 min after administration of ciraparantag/placebo, which is subsequently sustained after 30 min through to at least 6 h after ciraparantag/placebo dosing measured using PoC Coagulometer at Screening until the follow-up visit (up to 6 days post-discharge);Statistical analysis of the proportion of subjects who achieve a WBCT = the upper limit of normal (295 secs) within 15 min after administration of ciraparantag/placebo, which is subsequently sustained after 15 min through to at least 6 h after ciraparantag/placebo dosing, measured using PoC Coagulometer at Screening until the follow-up visit (up to 6 days post-discharge);Statistical analysis of the proportion of subjects who achieve a WBCT = the upper limit of normal (295 secs) at each of the planned WBCT assessment time points: 15 min, 30 min, 1 h, 3 h, 6 h and 24 h after administration of ciraparantag/placebo (relative to the end of infusion) measured using PoC Coagulometer at Screening until the follow-up visit (up to 6 days post-discharge);To provide additional safety and tolerability information for ciraparantag, measured using the incidence of AEs, treatment-emergent AEs and SAEs, changes from baseline in vital signs, electrocardiograms (ECGs), physical examinations and changes from baseline in laboratory safety tests at Day -1 until the follow-up visit (up to 6 days post-discharge);PK parameters for ciraparantag and metabolite (1,4-bis (3- aminopropyl) piperazine [BAP]), including the following: tmax, Cmax, AUC(0-last), AUC(0-inf), ?z, t1/2, CL and Vz measured using Serum concentration data at Day 4 until discharge;PK parameters for edoxaban, apixaban, and rivaroxaban, including the following: tmax, Cmax, and CL/F measured using Plasma concentration-time data at Day 4 until discharge | — |
Countries
England, United Kingdom
Contacts
Public ContactJeff Pilot
Outcome results
None listed