Clinical trial NCT01928147: A Phase 1a/1b Study of PPI-383 in Healthy Adults and Hepatitis C Patients
Official title: A Phase Ia and Ib Dose-Ranging Study to Assess the Safety, Pharmacokinetics, and Antiviral Efficacy of PPI-383 in Healthy Adults and Hepatitis C Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C, Chronic
Keywords: NS5B polymerase inhibitor
Phase 1
Genotype 1
Lead sponsor: Presidio Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2013-08-23
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Part I volunteers (single and multiple dose) - key inclusion criteria

* Healthy males
* Age 18 to 55 years
* Body mass index (BMI)18 to 32 kg/m2

Part II patients- key inclusion criteria

* 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.

Part II patients - key exclusion criteria

* 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

Primary outcomes:
measure: Safety and tolerability, as measured by clinical adverse events and laboratory assessments
timeFrame: Part I, up to day 12; and Part II, up to day 17
Secondary outcomes:
measure: PPI-383 plasma levels
timeFrame: Part I, up to day 12; and Part II, up to day 17
measure: serum HCV RNA levels
timeFrame: Part II, up to day 17
Other outcomes:
Locations:
city: Phoenix
country: Mauritius
facility: Investigational site
city: London
country: United Kingdom
facility: Investigational site
city: London
country: United Kingdom
facility: Investigational site
city: London
country: United Kingdom
facility: Investigational site
city: London
country: United Kingdom
facility: Investigational site
city: Nottingham
country: United Kingdom
facility: Investigational site
Study officials:
affiliation: Presidio Pharmaceuticals
name: Nathaniel Brown, M.D.
role: STUDY_DIRECTOR
References: