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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase Ia and Ib Dose-Ranging Study to Assess the Safety, Pharmacokinetics, and Antiviral Efficacy of PPI-383 in Healthy Adults and Hepatitis C Patients

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: PPI-383
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PPI-383 single dose escalation in healthy volunteers<br>There will be up to 10 sequential single dose cohorts to assess the bioavailability of different doses and formulations; a food effect cohort will be included. | Drug: PPI-383<br> <br> Drug: Placebo<br> <br> |
| Experimental: PPI-383 multiple doses in healthy volunteers<br>Upon completion of the single dose cohorts, an additional cohort will receive the highest well-tolerated dose from the single dose cohorts or placebo once daily for five days; up to additional cohorts may receive multiple doses of different formulations or different regimens | Drug: PPI-383<br> <br> Drug: Placebo<br> <br> |
| Experimental: PPI-383 multiple dose escalation in HCV Subjects<br>Upon completion of the single and multiple dose healthy volunteer cohorts, there will be 3, and potentially 4, sequential cohorts of HCV patients | Drug: PPI-383<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NS5B polymerase inhibitor, Phase 1, Genotype 1