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

Presidio Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Hepatitis C, Chronic

Treatments: Drug: Placebo; Drug: PPI-383

Study type: Interventional

Funder types: Industry

Identifiers

NCT01928147

PPI-383-101

Details and patient eligibility

About

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.

Enrollment: 114 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

114 participants in 3 patient groups

PPI-383 single dose escalation in healthy volunteers

Experimental group

Description:

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.

Treatment:

Drug: PPI-383

Drug: Placebo

PPI-383 multiple doses in healthy volunteers

Experimental group

Description:

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

Treatment:

Drug: PPI-383

Drug: Placebo

PPI-383 multiple dose escalation in HCV Subjects

Experimental group

Description:

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

Treatment:

Drug: PPI-383

Drug: Placebo