A Phase 1a/1b Study of PPI-383 in Healthy Adults and Hepatitis C Patients

NCT01928147 | Completed Phase 1

• 1 other identifier: PPI-383-101
• Study Type: interventional
• Target: 114
• Locations: 2 countries
• Sites: 6

Brief Summary

PPI-383 is an antiviral agent (an inhibitor of the hepatitis C virus NS5B polymerase) that is being developed as a potential treatment for hepatitis C virus infection. This study is being done to assess the dose-related safety and tolerance of PPI-383 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-383 is absorbed into the bloodstream. In Part II, the dose-related effect of PPI-383 on the amount of hepatitis C virus in patients' bloodstream (serum HCV RNA levels) also will be assessed.

Conditions

Hepatitis C, Chronic

Keywords

NS5B polymerase inhibitor; Phase 1; Genotype 1

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-383 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)

PPI-383 single dose escalation in healthy volunteers

EXPERIMENTAL

There will be up to 10 sequential single dose cohorts to assess the bioavailability of different doses and formulations; a food effect cohort will be included.

Drug: PPI-383; Drug: Placebo

PPI-383 multiple doses in healthy volunteers

EXPERIMENTAL

Upon completion of the single dose cohorts, an additional cohort will receive the highest well-tolerated dose from the single dose cohorts or placebo once daily for five days; up to additional cohorts may receive multiple doses of different formulations or different regimens

Drug: PPI-383; Drug: Placebo

PPI-383 multiple dose escalation in HCV Subjects

EXPERIMENTAL

Upon completion of the single and multiple dose healthy volunteer cohorts, there will be 3, and potentially 4, sequential cohorts of HCV patients

Drug: PPI-383; Drug: Placebo

Interventions

PPI-383 DRUG

PPI-383 multiple dose escalation in HCV Subjects; PPI-383 multiple doses in healthy volunteers; PPI-383 single dose escalation in healthy volunteers

Placebo DRUG

PPI-383 multiple dose escalation in HCV Subjects; PPI-383 multiple doses in healthy volunteers; PPI-383 single dose escalation in healthy volunteers

Eligibility Criteria

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

You may qualify if:

• Healthy males
• Age 18 to 55 years
• Body mass index (BMI)18 to 32 kg/m2
• Males, or females of non-childbearing potential
• Age 18 to 65 years
• Chronic hepatitis C, and absence of other known liver disease
• Seropositive for HCV antibody (HCV Ab) or HCV RNA at least once previously
• Seropositive for HCV Ab at screening
• Serum HCV RNA \> 5 log10 IU/mL at screening
• HCV gt-1
• Treatment-naïve for hepatitis C:
• BMI 18 to 35 kg/m2
• Otherwise in good health, without severe or clinically significant chronic or recurrent conditions requiring frequent medical intervention or continual pharmacologic management, except for anti-hypertensive use
• No medical or psychosocial conditions that would potentially interfere with the subject's ability to comply with the study assessments or visit schedule.

You may not qualify if:

• Seropositive for human immunodeficiency virus (HIV) antibody or hepatitis B virus (HBV) surface antigen (HBsAg)
• Signs or symptoms of decompensated liver disease
• Evidence of cirrhosis or hepatocellular carcinoma
• Diabetes Mellitus treated with insulin or hypoglycemic agents
• Asthma requiring hospital admission within the preceding 12 months
• History of alcohol abuse or illicit drug use which could interfere with a patient's compliance with the protocol requirements
• Any of the following laboratory values at screening
• Haemoglobin (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 \> upper limit of normal (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 screening

Sponsors & Collaborators

• Presidio Pharmaceuticals, Inc.: lead

Study Sites (6)

Investigational site

Phoenix, Mauritius

Location

Investigational site

London, NW3 2QG, United Kingdom

Location

Investigational site

London, SE5 9RS, United Kingdom

Location

Investigational site

London, UE1 2AD, United Kingdom

Location

Investigational site

London, W2 1NY, United Kingdom

Location

Investigational site

Nottingham, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Condition Hierarchy (Ancestors)

Hepatitis C; 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

  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: August 19, 2013
• First Posted: August 23, 2013
• Study Start: August 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: November 1, 2015
• Last Updated: November 26, 2015

Record last verified: 2015-11

Locations

MA (1); GB (5)