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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01448200




Registration number
NCT01448200
Ethics application status
Date submitted
5/10/2011
Date registered
7/10/2011
Date last updated
16/11/2012

Titles & IDs
Public title
A Phase 1 Study of PPI-668 in Healthy Volunteers and Patients With Hepatitis C Virus (HCV) Genotype 1
Scientific 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
Secondary ID [1] 0 0
PPI-668-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PPI-668
Treatment: Drugs - Placebo

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

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

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


Treatment: Drugs: PPI-668
capsules

Treatment: Drugs: Placebo
capsules
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability, as measured by clinical adverse events and laboratory assessments
Timepoint [1] 0 0
Part I, up to day 12; and Part II, up to day 17
Secondary outcome [1] 0 0
PPI-668 plasma levels
Timepoint [1] 0 0
Part I, up to day 12; and Part II, up to day 17
Secondary outcome [2] 0 0
serum HCV RNA levels
Timepoint [2] 0 0
Part II, up to day 17

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2012
Sample size
Target
Accrual to date
Final
82
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational site - Canberra
Recruitment postcode(s) [1] 0 0
- Canberra
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
New Zealand
State/province [3] 0 0
Auckland
Country [4] 0 0
New Zealand
State/province [4] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Presidio Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01448200
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nathaniel Brown, M.D.
Address 0 0
Presidio Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01448200