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

Sponsor

Presidio Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01448200

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

11.7

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: PPI-668 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

82 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, 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

Study Start Date :

Oct 1, 2011

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

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.

Key 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

Contacts and Locations

Locations

	Site	City	State	Country
1	Investigational site	Costa Mesa	California	United States
2	Investigational site	Sacramento	California	United States
3	Investigational site	San Francisco	California	United States
4	Investigational Site	San Antonio	Texas	United States
5	Investigational site	Canberra		Australia
6	Investigational site	Auckland		New Zealand
7	Investigational site	Christchurch		New Zealand