Hepatitis C, Chronic
Conditions
Keywords
NS5B polymerase inhibitor, Phase 1, Genotype 1
Brief summary
PPI-383 is an antiviral agent (an inhibitor of the hepatitis C virus NS5B polymerase) that is being developed as a potential treatment for hepatitis C virus infection. This study is being done to assess the dose-related safety and tolerance of PPI-383 when given to healthy volunteers for up to 5 days (Part I of the study) and to hepatitis C patients for up to 3 days (Part II). In addition, the study will assess how much PPI-383 is absorbed into the bloodstream. In Part II, the dose-related effect of PPI-383 on the amount of hepatitis C virus in patients' bloodstream (serum HCV RNA levels) also will be assessed.
Interventions
DRUGPPI-383
DRUGPlacebo
Sponsors
Presidio Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability, as measured by clinical adverse events and laboratory assessments | Part I, up to day 12; and Part II, up to day 17 |
Secondary
| Measure | Time frame |
|---|---|
| PPI-383 plasma levels | Part I, up to day 12; and Part II, up to day 17 |
| serum HCV RNA levels | Part II, up to day 17 |
Countries
Mauritius, United Kingdom
Outcome results
None listed