Resumen

Este es un estudio global, multicéntrico, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos con avatrombopag para tratar adultos con trombocitopenia asociada a enfermedad hepática. El estudio evaluará avatrombopag en el tratamiento de la trombocitopenia asociada a enfermedad hepática previa a un procedimiento electivo, con el objetivo de reducir la necesidad de transfusiones de plaquetas o cualquier procedimiento de rescate para el sangrado debido a complicaciones hemorrágicas procedimentales y postprocedimentales. Los participantes serán enrolados en 2 cohortes según el recuento medio basal de plaquetas y, dentro de cada cohorte de recuento basal de plaquetas, serán estratificados según el riesgo de sangrado asociado al procedimiento electivo (bajo, moderado o alto) y el estado de carcinoma hepatocelular (HCC) (sí o no).

Descripción detallada

Este estudio constará de 3 fases: prerandomización, randomización y una fase de seguimiento. La fase de prerandomización incluye una visita de selección que tendrá lugar desde el Día -14 hasta el Día -1; la fase de randomización incluye el período basal, el período de tratamiento y el período del día del procedimiento (5 a 8 días después de la última dosis del medicamento del estudio [Día de estudio 10 a 13]). La fase de seguimiento comprende 2 visitas: 7 días después del día del procedimiento y 30 días después de recibir la última dosis del medicamento del estudio. Los procedimientos permitidos incluyen: paracentesis; toracocentesis; endoscopía gastrointestinal con o sin planes de biopsia, colonoscopía, polipectomía o ligadura de várices; biopsia hepática; broncoscopía con o sin planes de biopsia; ablación con etanol o quimioembolización para HCC; cateterización vascular (incluyendo procedimientos del lado derecho en participantes con hipertensión pulmonar); derivación portosistémica intrahepática transyugular; procedimientos dentales; biopsia renal; intervenciones biliares; colocación de tubo de nefrostomía; ablación por radiofrecuencia; e intervenciones laparoscópicas.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Participants greater than or equal to 18 years of age at Screening with chronic liver disease
Participants who have a mean baseline platelet count of less than 50 x 10\^9/L. Platelet counts must be measured on 2 separate occasions, during the Screening Period and at Baseline, and must be performed at least one day apart with neither platelet count greater than 60 x 10\^9/L. The mean of these 2 platelet counts (mean baseline platelet count) will be used for entry criteria and for assignment to the low or high baseline platelet count cohort.
Participants scheduled to undergo a permitted elective procedure who, in the opinion of the investigator, will require a platelet transfusion to address a risk of bleeding associated with the procedure unless there is a clinically significant increase in platelet count from baseline
Model For End-stage Liver Disease (MELD) score less than or equal to 24 at Screening
If taking inhibitors of P glycoprotein (P-gp), except for verapamil, dose must be stable for 7 days prior to Screening
Provide written informed consent
Willing and able to comply with all aspects of the protocol

Criterios de exclusión

Any history of arterial or venous thrombosis, including partial or complete thrombosis
Evidence of thrombosis (partial or complete) in the main portal vein, portal vein branches, or any part of the splenic mesenteric system at Screening
Portal vein blood flow velocity rate \<10 centimeters/second at Screening
Hepatic encephalopathy that cannot be effectively treated
Participants with HCC with Barcelona Clinic Liver Cancer (BCLC) staging classification C or D
Platelet transfusion or receipt of blood products containing platelets within 7 days of Screening. However packed red blood cells are permitted.
Heparin, warfarin, nonsteroidal anti-inflammatory drugs (NSAID), aspirin, verapamil, and antiplatelet therapy with ticlopidine or glycoprotein IIb/IIIa antagonists (eg, tirofiban) within 7 days of Screening
Use of erythropoietin stimulating agents within 7 days of Screening
Interferon (IFN) use within 14 days of Screening
Estrogen-containing hormonal contraceptive or hormone replacement therapy use within 30 days of Screening
Active infection requiring systemic antibiotic therapy within 7 days of Screening. However, prophylactic use of antibiotics is permitted.
Alcohol abuse, alcohol dependence syndrome, drug abuse, or drug dependence within 6 months of the study start (unless participating in a controlled rehabilitation program) or acute alcoholic hepatitis (chronic alcoholic hepatitis is allowed) within 6 months of the study start
Elective procedure performed prior to Visit 4 (Procedure Day)
Known to be human immunodeficiency virus positive
Any clinically significant acute or active bleeding (eg, gastrointestinal, central nervous system)
Known history of any primary hematologic disorder (eg, immune thrombocytopenic purpura, myelodysplastic syndrome)
Known medical history of genetic prothrombotic syndromes (eg, Factor V Leiden; prothrombin G20210A; ATIII deficiency, etc.)
Participants with a history of significant cardiovascular disease (eg, congestive heart failure New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events \[eg, atrial fibrillation\], coronary artery stent placement, angioplasty, and coronary artery bypass grafting)
Females of childbearing potential who have had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method \[such as condom plus diaphragm with spermicide\], a progesterone-only contraceptive implant/injection, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the participant must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea in the appropriate age group and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) at least 1 month before dosing.
Females who are lactating or pregnant at Screening or Baseline (as documented by a positive serum beta-human chorionic gonadotropin \[B-hCG\] test with a minimum sensitivity 25 IU/L or equivalent units of B-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
Post liver transplant participants
Any participant who has previously received avatrombopag
Hypersensitivity to avatrombopag maleate or any of its excipients
Hemoglobin levels ≤ 8.0 or ≥ 18.0 g/dL for men and \> 15 for women at Screening, with hematocrit ≥ 54% for men and ≥ 45% for women
Current malignancy including solid tumors and hematologic malignancies (except HCC)
Any history of concomitant medical condition that, in the opinion of the investigator(s), would compromise the participant's ability to safely complete the study
Currently enrolled in another clinical trial with any investigational drug or device within 30 days of Screening

Intervenciones

drug

avatrombopag (lower baseline platelet count)

60 mg avatrombopag (3 x 20 mg tablets)

drug

placebo (lower baseline platelet count)

60 mg placebo (3 x 20 mg matching placebo tablets)

drug

avatrombopag (higher baseline platelet count)

40 mg avatrombopag (2 x 20 mg tablets)

drug

placebo (higher baseline platelet count)

40 mg placebo (2 x 20 mg matching placebo tablets)

Estudio aleatorizado, global, doble ciego, controlado con placebo, de grupos paralelos para evaluar la eficacia y seguridad de avatrombopag oral una vez al día para el tratamiento de adultos con trombocitopenia asociada a enfermedad hepática previa a un procedimiento electivo

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

avatrombopag (lower baseline platelet count)

placebo (lower baseline platelet count)

avatrombopag (higher baseline platelet count)

placebo (higher baseline platelet count)

Ubicaciones

Patrocinadores