Hereditary Angioedema MedDRA version: 16.1 Level: PT Classification code 10019860 Term: Hereditary angioedema System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: BCX4161
Product Code: BCX4161
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: BCX4161
Current Sponsor code: BCX4161
Other descriptive name: BCX4161
Concentration unit: mg milligr
Sponsors
BioCryst Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and non-pregnant, non-lactating females of age 18-65 years 2. A clinical diagnosis of hereditary angioedema as documented at any time in the medical records or at screening by a low C4 level AND: a. A low C1INH antigenic level OR b. A normal or increased C1INH antigenic level and a low C1INH functional level 3. Documentation of an average of 1 attack per week over at least a 3 month period within the past year 4. Body mass index (BMI) of 19-36 kg/m2 5. Female participants must meet one of the following requirements: a. A woman of childbearing potential (defined as a nonmenopausal female who has not had a hysterectomy, bilateral oophorectomy, or documented ovarian failure) who agrees to use 2 highly effective contraceptive methods for the study duration and for 30 days after study drug dosing. Two or more of the following methods are acceptable and must include at least one barrier method: Surgical sterilization (i.e. bilateral tubal ligation), placement of an intrauterine device or intrauterine system, hormonal contraception (implantable, patch, oral, vaginal ring), barrier methods (either their partners use of a condom or the subjects use of an occlusive cap [diaphragm, or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository). Estrogen-and progestin containing hormonal contraception is only permitted if it has been used for at least 60 days prior to screening (IUDs with progestin are permitted to be placed at any time prior to or during screening). Female subjects who report being postmenopausal for = 2 years and have a screening follicle stimulating hormone (FSH) = 40 mIU/mL must agree to use 2 highly effective contraceptive methods for the study period and for 30 days after the last dose of study drug (as defined above). b. A woman of nonchildbearing potential (defined as postmenopausal for > 2 years or a screening FSH > 40 mIU/mL if postmenopausal for = 2 years or have had a hysterectomy, bilateral oophorectomy, or documented ovarian failure) 6. Male participants must comply with the following requirements: a. Must agree to utilize a highly effective contraceptive method with female partners of childbearing potential (defined as postmenopausal = 2 years or a nonmenopausal female who has not had a hysterectomy, bilateral oophorectomy, or documented ovarian failure), where “highly effective contraceptive method” is defined as having had a vasectomy, or utilizing 2 forms of contraception, 1 of which must be a condom, during intercourse, for the study duration and for 90 days after the last dose of the study drug. b. Must abstain from sperm donation for the study period and for 90 days after the last dose of study drug 7. Any concomitant medication at screening must be anticipated to be continued through the study and be of a stable dose and regimen for the duration of the study 8. Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Age 65 years 2. Females who are pregnant (positive urine or serum pregnancy test) or breast feeding at screening or who are planning to become pregnant during the study period 3. Any clinically significant medical condition or medical history that, in the opinion of the Investigator or Sponsor, would interfere with the subject’s safety or ability to participate in the study 4. Dementia, altered mental status or any psychiatric condition, or stay in an institution further to an official or court order that would prohibit the understanding or rendering of informed consent 5. Use of an estrogen-or porgestin containing hormonal contraceptive that was initiated less than 60 days prior to screening. IUDs containing progestin can be placed at any time prior to or during the screening period. 6. Use within the 7 days prior to screening or planned use through the study of C1 inhibitor (C1 INH) or tranexamic acid for prophylaxis of HAE attacks. Use of a C1INH therapy for treatment of acute attacks is not excluded 7. Use within the 30 days prior to screening or planned use through the study of anabolic steroids for prophylaxis of HAE attacks 8. Concurrent daily use of anticoagulants, antiplatelet drugs (with the exception of low-dose aspirin for cardioprotection) or NSAIDS from screening through the end of the study 9. Abnormal ECG (defined as any screening or baseline QTcF > 470 msec, PR > 220msec, or ventricular and/or atrial premature contractions that are more frequent than occasional, and/or as couplets or higher in grouping) 10. Family history of sudden death to causes other than HAE 11. History of QT prolongation 12. Any abnormal laboratory or urinalysis finding at screening that, in the opinion of the Investigator or Sponsor, is clinically significant and relevant for this study 13. Prolonged activated partial thromboplastin time (aPTT) or prothrombin time (PT) at screening (defined as any screening or baseline Grade 1 or greater toxicity) 14. Current participation in any other investigational drug study or within the past 30 days of screening 15. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse (self-reported alcoholic intake > 3 units alcohol/day) 16. Positive for hepatitis B surface antigen (HBV), hepatitis C antibody (HCV), or human immunodeficiency virus (HIV) type 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of prophylactic BCX4161 as measured by the frequency of attacks in subjects with hereditary angioedema (HAE);Secondary Objective: To evaluate the safety and tolerability of prophylactic BCX4161 in subjects with HAE type 1 or 2 To describe the pharmacokinetics of BCX4161 in subjects with HAE type 1 or 2 To characterize the pharmacodynamic effects of BCX4161in subjects with HAE ;Primary end point(s): Number of acute attacks (independently adjudicated) Symptoms and location of any attack Severity of any attack (using the Angioedema Activity Score- AAS) Treatment used to manage any attack ;Timepoint(s) of evaluation of this end point: At the end of each 28 day treatment period - ie Day 29 and Day 64 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): AEs, laboratory analyses (clinical chemistry, hematology and urinalysis), vital signs, ECGs and physical examinations Pharmacokinetic endpoints kallikrein inhibition by BCX4161 Prothrombin time, activated partial prothrombin time;Timepoint(s) of evaluation of this end point: Throughout the treatment periods, and seven days post final dose | — |
Countries
Germany, United Kingdom
Contacts
Public ContactClinical Operations
AMS Advanced Medical Services
Outcome results
None listed