Table 2.

Summary of findings in the GLP repeat-dose toxicology study in cynomolgus monkey.

ParameterFindings
Clinical observations
  • Mean body weight increased in all dose groups; however, minimal decrease in overall body weight gain at 10 mg/kg

  • Dose-dependent hyperpigmentation and dry skin. Erythema at locations of dry skin at ≥ 6 mg/kg. Resolved during recovery

Clinical pathology
  • Transient decrease in neutrophil counts at ≥ 6 mg/kg, minimal/mild decrease in lymphocytes at 10 mg/kg. Lacked microscopic correlates, resolved during recovery

  • Decrease in red cell mass associated with increase in reticulocytes; less pronounced increase in reticulocytes at ≥ 6 mg/kg. Fully resolved during recovery

  • Increased C-reactive protein and fibrinogen. Resolved at subsequent collections

  • Transient minimal/mild increases in AST and/or ALT. Lacked correlative microscopic findings in the liver or muscle, resolved at subsequent collections

Gross pathology
  • Skin hyperpigmentation most prominent on limbs and head at ≥ 1 mg/kg. Generally dose dependent in incidence and severity. Ongoing reversibility during recovery

Histopathology
  • Skin epidermal hyperplasia, lymphocytic infiltrate, single-cell necrosis and increased pigment most prominent at ≥ 6 mg/kg. Ongoing resolution during recovery

  • Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase.