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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Presidio Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01448200
First received: October 5, 2011
Last updated: November 14, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: PPI-668
Drug: Placebo
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Presidio Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Safety and tolerability, as measured by clinical adverse events and laboratory assessments [ Time Frame: Part I, up to day 12; and Part II, up to day 17 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • PPI-668 plasma levels [ Time Frame: Part I, up to day 12; and Part II, up to day 17 ] [ Designated as safety issue: No ]
  • serum HCV RNA levels [ Time Frame: Part II, up to day 17 ] [ Designated as safety issue: No ]

Enrollment: 82
Study Start Date: October 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part I: single dose escalation in healthy volunteers

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
capsules
Drug: Placebo
capsules
Experimental: Part I: multiple dose administration to healthy volunteers

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
capsules
Drug: Placebo
capsules
Experimental: Part II: multiple dose escalation in HCV subjects

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
capsules
Drug: Placebo
capsules

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01448200

Locations
United States, California
Investigational site
Costa Mesa, California, United States
Investigational site
Sacramento, California, United States
Investigational site
San Francisco, California, United States
United States, Texas
Investigational Site
San Antonio, Texas, United States
Australia
Investigational site
Canberra, Australia
New Zealand
Investigational site
Auckland, New Zealand
Investigational site
Christchurch, New Zealand
Sponsors and Collaborators
Presidio Pharmaceuticals, Inc.
Investigators
Study Director: Nathaniel Brown, M.D. Presidio Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Presidio Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01448200     History of Changes
Other Study ID Numbers: PPI-668-101
Study First Received: October 5, 2011
Last Updated: November 14, 2012
Health Authority: New Zealand: Medsafe
New Zealand: Health and Disability Ethics Committees
United States: Food and Drug Administration
United States: Institutional Review Board
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee

Keywords provided by Presidio Pharmaceuticals, Inc.:
hepatitis C
NS5A inhibitor
Phase 1
genotype-1
genotype-2
genotype-3

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Chronic
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 21, 2014