A Phase 1 Study of PPI-668 in Healthy Volunteers and Patients With Hepatitis C Virus (HCV) Genotype 1
- Registration Number
- NCT01448200
- Lead Sponsor
- Presidio Pharmaceuticals, Inc.
- Brief Summary
PPI-668 is an antiviral agent (a hepatitis C NS5A inhibitor) that is being developed as a potential treatment for hepatitis C virus infection. This study is being done to assess the safety and tolerance of PPI-668 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-668 is absorbed into the bloodstream. In Part II, the effect of PPI-668 on the amount of hepatitis C virus in patients' bloodstream (serum HCV RNA levels) also will be assessed.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
Inclusion Criteria
Not provided
Exclusion Criteria
- Seropositive for HIV antibody, or HBV surface antigen (HBsAg) at Screen. Volunteer subjects for Part I must also be negative for HCV antibody.
- Any medical condition that may interfere with the absorption, distribution or elimination of study drug (PPI-668), or with the clinical and laboratory assessments in this study.
- Poorly controlled or unstable hypertension; or sustained systolic BP > 150 or diastolic BP > 95 at Screen.
- History of Diabetes Mellitus treated with insulin or hypoglycemic agents
- History of alcohol abuse or illicit drug use which, in the investigator's judgment, could interfere with a patient's compliance, with the protocol requirements or with the safety or efficacy assessments of the study
- History of malignancy unless the malignancy has been in complete remission and without additional medical or surgical interventions during the preceding three years
- No clinically significant laboratory abnormalities at Screen for healthy volunteers in Part I. For Screen laboratory parameters for HCV patients in Part II, refer to the 'Additional Criteria for HCV Patients' below.
Additional Key Entry Criteria for HCV patients (Part II):
-
Clinical diagnosis of chronic hepatitis C, documented by:
- Clinical findings compatible with chronic hepatitis C, and absence of other known liver disease
- Seropositive for HCV antibody or HCV RNA at least once previously, and at Screen
- Serum HCV RNA > 5 log10 IU/mL at Screen, by the PCR assay at the central study laboratory
- HCV genotype-1 (1a or 1b, or non-subtypable genotype-1), or HCV genotype-2a or genotype-3a
-
ALT must be <5 x ULN at screen
-
No previous treatment with interferon, pegIFN, or ribavirin for genotype-1 patients
-
No history of signs or symptoms of decompensated liver disease
-
Any of the following laboratory values at Screening will be exclusionary for study participation:
- 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 >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 Screen
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part I: single dose escalation in healthy volunteers PPI-668 There will be three sequential single dose cohorts: Cohort A: PPI-668 dose D1 or placebo Cohort B: PPI-668 dose D2 or placebo Cohort C: PPI-668 dose D3 or placebo Part I: single dose escalation in healthy volunteers Placebo There will be three sequential single dose cohorts: Cohort A: PPI-668 dose D1 or placebo Cohort B: PPI-668 dose D2 or placebo Cohort C: PPI-668 dose D3 or placebo Part I: multiple dose administration to healthy volunteers PPI-668 Upon completion of the single dose escalation phase, an additional cohort will receive repeat doses: Cohort D: highest well-tolerated dose from Cohorts A-C or placebo once daily for five days Part I: multiple dose administration to healthy volunteers Placebo Upon completion of the single dose escalation phase, an additional cohort will receive repeat doses: Cohort D: highest well-tolerated dose from Cohorts A-C or placebo once daily for five days Part II: multiple dose escalation in HCV subjects PPI-668 Upon completion of Part I, there will be 3, and potentially 4, sequential cohorts of HCV patients: Cohort E (genotype-1): PPI-668 dose E1 or placebo Cohort F (genotype-1): PPI-668 dose E2 or placebo Cohort G (genotype-1): PPI-668 dose E3 or placebo Cohort H (genotype-1): if necessary for dose-response assessment; dose to be determined Cohort I (genotype-2 or -3): PPI-668 dose E4 or placebo Part II: multiple dose escalation in HCV subjects Placebo Upon completion of Part I, there will be 3, and potentially 4, sequential cohorts of HCV patients: Cohort E (genotype-1): PPI-668 dose E1 or placebo Cohort F (genotype-1): PPI-668 dose E2 or placebo Cohort G (genotype-1): PPI-668 dose E3 or placebo Cohort H (genotype-1): if necessary for dose-response assessment; dose to be determined Cohort I (genotype-2 or -3): PPI-668 dose E4 or placebo
- Primary Outcome Measures
Name Time Method 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
Name Time Method PPI-668 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
Trial Locations
- Locations (2)
Investigational site
🇳🇿Christchurch, New Zealand
Investigational Site
🇺🇸San Antonio, Texas, United States