Clinical trial NCT01448200: A Phase 1 Study of PPI-668 in Healthy Volunteers and Patients With Hepatitis C Virus (HCV) Genotype 1
Official title: A Phase 1 Dose-Ranging Study to Assess the Safety, Pharmacokinetics and Antiviral Efficacy of PPI-668 in Healthy Volunteers and Patients With HCV Genotype-1 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C, Chronic
Keywords: hepatitis C
NS5A inhibitor
Phase 1
genotype-1
genotype-2
genotype-3
Lead sponsor: Presidio Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-10-07
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: In order to participate in the study, volunteers for Part I and patients for Part II must meet all of the following key entry criteria, as well as other entry criteria specified in the full protocol:

Key Inclusion Criteria

1. Male or female, between 18 and 65 years of age. Female patients must be surgically sterile or two years post-menopausal.
2. Body Mass Index (BMI) 18 - 35 kg/m2
3. In good health, in the judgment of the Principal Investigator
4. Able and willing to comply with all protocol requirements and to sign an informed consent.

Key Exclusion Criteria:

1. Seropositive for HIV antibody, or HBV surface antigen (HBsAg) at Screen. Volunteer subjects for Part I must also be negative for HCV antibody.
2. 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.
3. Poorly controlled or unstable hypertension; or sustained systolic BP \> 150 or diastolic BP \> 95 at Screen.
4. History of Diabetes Mellitus treated with insulin or hypoglycemic agents
5. 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
6. History of malignancy unless the malignancy has been in complete remission and without additional medical or surgical interventions during the preceding three years
7. 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):

1. Clinical diagnosis of chronic hepatitis C, documented by:

   1. Clinical findings compatible with chronic hepatitis C, and absence of other known liver disease
   2. Seropositive for HCV antibody or HCV RNA at least once previously, and at Screen
   3. Serum HCV RNA \> 5 log10 IU/mL at Screen, by the PCR assay at the central study laboratory
   4. HCV genotype-1 (1a or 1b, or non-subtypable genotype-1), or HCV genotype-2a or genotype-3a
2. ALT must be \<5 x ULN at screen
3. No previous treatment with interferon, pegIFN, or ribavirin for genotype-1 patients
4. No history of signs or symptoms of decompensated liver disease
5. 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

Primary outcomes:
measure: Safety and tolerability, as measured by clinical adverse events and laboratory assessments
timeFrame: Part I, up to day 12; and Part II, up to day 17
Secondary outcomes:
measure: PPI-668 plasma levels
timeFrame: Part I, up to day 12; and Part II, up to day 17
measure: serum HCV RNA levels
timeFrame: Part II, up to day 17
Other outcomes:
Locations:
city: Costa Mesa
country: United States
facility: Investigational site
state: California
city: Sacramento
country: United States
facility: Investigational site
state: California
city: San Francisco
country: United States
facility: Investigational site
state: California
city: San Antonio
country: United States
facility: Investigational Site
state: Texas
city: Canberra
country: Australia
facility: Investigational site
city: Auckland
country: New Zealand
facility: Investigational site
city: Christchurch
country: New Zealand
facility: Investigational site
Study officials:
affiliation: Presidio Pharmaceuticals, Inc.
name: Nathaniel Brown, M.D.
role: STUDY_DIRECTOR
References: