title: A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia.
abstract: 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 (160mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. Another 12 subjects received either a high dose (320mg/kg) of SANGUINATE or 15mg/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.
authors.affiliation: Prolong Pharmaceuticals, South Plainfield, United States. Electronic address: hmisra@prolongpharma.com.
authors.forename: Hemant
authors.initials: H
authors.lastname: Misra
authors.affiliation: Prolong Pharmaceuticals, South Plainfield, United States.
authors.forename: James
authors.initials: J
authors.lastname: Bainbridge
authors.affiliation: Prolong Pharmaceuticals, South Plainfield, United States.
authors.forename: John
authors.initials: J
authors.lastname: Berryman
authors.affiliation: Prolong Pharmaceuticals, South Plainfield, United States.
authors.forename: Abraham
authors.initials: A
authors.lastname: Abuchowski
authors.affiliation: Hospital Pablo Tobon Uribe, Medellin, Colombia.
authors.forename: Kenneth Mauricio
authors.initials: KM
authors.lastname: Galvez
authors.affiliation: Fundación Reina Isabel, Cali, Colombia.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Uribe
authors.affiliation: Fundación BIOS, Barranquilla, Colombia.
authors.forename: Angel Luis
authors.initials: AL
authors.lastname: Hernandez
authors.affiliation: Pan American Medical Research Institute, Pamri, Panama.
authors.forename: Nestor Rodolfo
authors.initials: NR
authors.lastname: Sosa
keywords: Clinical trial; SANGUINATE; Safety; Sickle cell disease