first in human study of als-002158; single dose, food effect in healthy volunteers; multiple doses in chronic hepatitis c genotype 1

Conditions: Hepatitis C, Chronic

Summary: this randomized, double-blind, placebo-controlled, 3-part study will assess the safety, tolerability, and pharmacokinetics of orally administered als-002158 in healthy volunteers (hv) and subjects with chronic hepatitis c (chc) genotype 1 infection. part 1 will assess single ascending dosing pharmacokinetics and safety in hv. part 2 will assess food effects on pharmacokinetics in hv. part 3 will assess multiple ascending dosing pharmacokinetics and safety in subjects with chc genotype 1 infection.


Eligibility criteria:
inclusion criteria: * subject has provided written consent. * subject is in good health as deemed by the investigator * creatinine clearance of greater than 50 ml/min (cockcroft- gault). * male or female, 18-55 years of age for hv and 18-65 years of age for subjects with chc. * body mass index (bmi) 18-32 kg/m2 inclusive for hv and 18-36 kg/m2 for subjects with chc, minimum weight 50 kg in both populations. * a female is eligible to participate in this study if she is of non-childbearing potential. * if male, subject is surgically sterile or practicing specific forms of birth control. additional inclusion criteria for subjects with chc genotype 1 infection: * positive hcv antibody and a positive hcv rna at screening. * documentation of chc infection of greater than 6 months duration at screening. * chc genotype 1 infection at screening. * hcv rna viral load ≥ 105 and ≤ 108 iu/ml using a sensitive quantitative assay * liver biopsy within two years or fibroscan evaluation within 6 months prior to screening that clearly excludes cirrhosis. fibroscan liver stiffness score must be \< 12 kpa. * absence of hepatocellular carcinoma as indicated by an abdominal ultrasound scan during screening. * no prior treatment for chc. * absence of history of clinical hepatic decompensation. * laboratory values include: * prothrombin time \< 1.5 × uln. * platelets \> 120,000/mm3. * albumin \> 3.5 g/dl, bilirubin \< 1.5 mg/dl at screening (subjects with documented gilbert's disease allowed). * serum alt concentration \< 5 × uln. * alpha fetoprotein (afp) concentration ≤ uln. if afp is ≥ uln, absence of a hepatic mass must be demonstrated by ultrasound within the screening period. exclusion criteria: * clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, thyroid, or any uncontrolled medical illness or psychiatric disorder. * positive test for hav igm, hbsag, hcv ab (hv only), or hiv ab. * abnormal screening laboratory results that are considered clinically significant by the investigator. * clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, including those experienced in previous trials with experimental drugs. * participation in an investigational drug trial or having received an investigational vaccine within 30 days or 5 half lives (whichever is longer) prior to receiving study medication. * clinically significant blood loss or elective blood donation of significant volume. * laboratory abnormalities including: * thyroid stimulating hormone (tsh) \>uln. * hematocrit \< 34 %. * white blood cell counts \< 3,500/mm3. * for healthy volunteers, history of regular use of tobacco. * the subject has a positive pre-study drug screen.