A Phase 1 Study of PPI-668 in Healthy Volunteers and Patients With Hepatitis C Virus (HCV) Genotype 1

Hepatitis C, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01448200
• Other study ID #: PPI-668-101
• Status: Completed
• Phase: Phase 1
• First received: October 5, 2011
• Last updated: November 14, 2012
• Start date: October 2011
• Est. completion date: November 2012

Study information

• Verified date: November 2012
• Source: Presidio Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: New Zealand: MedsafeNew Zealand: Health and Disability Ethics CommitteesUnited States: Food and Drug AdministrationUnited States: Institutional Review BoardAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: Human Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• PPI-668
capsules
• Placebo
capsules

Locations

Country	Name	City	State
Australia	Investigational site	Canberra
New Zealand	Investigational site	Auckland
New Zealand	Investigational site	Christchurch
United States	Investigational site	Costa Mesa	California
United States	Investigational site	Sacramento	California
United States	Investigational Site	San Antonio	Texas
United States	Investigational site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Presidio Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	PPI-668 plasma levels		Part I, up to day 12; and Part II, up to day 17	No
Secondary	serum HCV RNA levels		Part II, up to day 17	No