A Phase 1a/1b Study of PPI-383 in Healthy Adults and Hepatitis C Patients

Part I volunteers (single and multiple dose) - key inclusion criteria

• Healthy males
• Age 18 to 55 years
• Body mass index (BMI)18 to 32 kg/m2

Part II patients- key inclusion criteria

• Males, or females of non-childbearing potential
• Age 18 to 65 years
• Chronic hepatitis C, and absence of other known liver disease
• Seropositive for HCV antibody (HCV Ab) or HCV RNA at least once previously
• Seropositive for HCV Ab at screening
• Serum HCV RNA > 5 log10 IU/mL at screening
• HCV gt-1
• Treatment-naïve for hepatitis C:
• BMI 18 to 35 kg/m2
• Otherwise in good health, without severe or clinically significant chronic or recurrent conditions requiring frequent medical intervention or continual pharmacologic management, except for anti-hypertensive use
• No medical or psychosocial conditions that would potentially interfere with the subject's ability to comply with the study assessments or visit schedule.

Part II patients - key exclusion criteria

• Seropositive for human immunodeficiency virus (HIV) antibody or hepatitis B virus (HBV) surface antigen (HBsAg)
• Signs or symptoms of decompensated liver disease
• Evidence of cirrhosis or hepatocellular carcinoma
• Diabetes Mellitus treated with insulin or hypoglycemic agents
• Asthma requiring hospital admission within the preceding 12 months
• History of alcohol abuse or illicit drug use which could interfere with a patient's compliance with the protocol requirements

• Any of the following laboratory values at screening

  • Haemoglobin (Hgb) <11 g/dL in women or 12 g/dL in men
  • White blood cell count <4,000/mm3
  • Absolute neutrophil count (ANC) < 1800 per mm3
  • Platelet count <100,000 per mm3
  • Serum creatinine > upper limit of normal (ULN) at the central study laboratory
  • Serum albumin <3.4 g/dL
  • Total bilirubin >2.0 mg/dL
• Clinically significant abnormality in the electrocardiograms (ECGs) at screening