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

NCT01448200 | Completed Phase 1 DMC

• 1 other identifier: PPI-668-101
• Study Type: interventional
• Target: 82
• Locations: 3 countries
• Sites: 7

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.

Conditions

Hepatitis C, Chronic

Keywords

hepatitis C; NS5A inhibitor; Phase 1; genotype-1; genotype-2; genotype-3

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (3)

Part I: single dose escalation in healthy volunteers

EXPERIMENTAL

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

Drug: PPI-668; Drug: Placebo

Part I: multiple dose administration to healthy volunteers

EXPERIMENTAL

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

Drug: PPI-668; Drug: Placebo

Part II: multiple dose escalation in HCV subjects

EXPERIMENTAL

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

Drug: PPI-668; Drug: Placebo

Interventions

PPI-668 DRUG

capsules

Part I: multiple dose administration to healthy volunteers; Part I: single dose escalation in healthy volunteers; Part II: multiple dose escalation in HCV subjects

Placebo DRUG

capsules

Part I: multiple dose administration to healthy volunteers; Part I: single dose escalation in healthy volunteers; Part II: multiple dose escalation in HCV subjects

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Presidio Pharmaceuticals, Inc.: lead

Study Sites (7)

Investigational site

Costa Mesa, California, United States

Location

Investigational site

Sacramento, California, United States

Location

Investigational site

San Francisco, California, United States

Location

Investigational Site

San Antonio, Texas, United States

Location

Investigational site

Canberra, Australia

Location

Investigational site

Auckland, New Zealand

Location

Investigational site

Christchurch, New Zealand

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

ravidasvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nathaniel Brown, M.D.

  Presidio Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2011
• First Posted: October 7, 2011
• Study Start: October 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: November 16, 2012

Record last verified: 2012-11

Locations

NZ (2); US (4); AU (1)