A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia
| Autor: | Kenneth Mauricio Galvez, Nestor Rodolfo Sosa, Angel Luis Hernandez, Luis Fernando Uribe, John Berryman, Hemant Misra, Abraham Abuchowski, James W B Bainbridge |
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| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_specialty
Urinalysis 030204 cardiovascular system & hematology Gastroenterology 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine Troponin I medicine Clinical endpoint Adverse effect SANGUINATE Hematology medicine.diagnostic_test lcsh:RC633-647.5 business.industry Sickle cell disease lcsh:Diseases of the blood and blood-forming organs medicine.disease Sickle cell anemia Surgery Clinical trial 030220 oncology & carcinogenesis Original Article Safety business |
| Zdroj: | Revista Brasileira de Hematologia e Hemoterapia Revista Brasileira de Hematologia e Hemoterapia v.39 n.1 2017 Revista brasileira de hematologia e hemoterapia Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular (ABHHTC) instacron:ABHHTC Revista Brasileira de Hematologia e Hemoterapia, Volume: 39, Issue: 1, Pages: 20-27, Published: MAR 2017 Revista Brasileira de Hematologia e Hemoterapia, Vol 39, Iss 1, Pp 20-27 |
| ISSN: | 1516-8484 |
| Popis: | Background Treatment of sickle cell anemia is a challenging task and despite the well understood genetic and biochemical pathway of sickle hemoglobin, current therapy continues to be limited to the symptomatic treatment of pain, supplemental oxygen, antibiotics, red blood cell transfusions and hydroxyurea. SANGUINATE is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities. Methods An open-label randomized Phase Ib study was performed in adult sickle cell anemia patients. Two dose levels of SANGUINATE were compared to hydroxyurea in 24 homozygotes for Hb SS. Twelve subjects received either a low dose (160 mg/kg) of SANGUINATE or 15 mg/kg hydroxyurea. Another 12 subjects received either a high dose (320 mg/kg) of SANGUINATE or 15 mg/kg hydroxyurea. The primary endpoint was the safety of SANGUINATE versus hydroxyurea in sickle cell anemia patients. Secondary endpoints included determination of the plasma pharmacokinetics and assessment of hematologic measurements. Results Musculoskeletal related adverse events were the most common. Transient troponin I levels increased in three patients, one of whom had an increase in tricuspid regurgitant velocity; however, no clinical signs were noted. Following an assessment of vital signs, tricuspid regurgitant velocity, electrocardiogram, serum biochemistry, hematology, urinalysis, and analysis of reported adverse events, SANGUINATE was found to be safe in stable sickle cell anemia patients. Conclusions The clinical trial met its primary objective of demonstrating an acceptable safety profile for SANGUINATE in patients with sickle cell anemia. This trial established the safety of SANGUINATE at both dose levels and permitted its advance to Phase II trials. |
| Databáze: | OpenAIRE |
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