A Randomized, Double-blind, Placebo-controlled, First-in-human, 3-Part Study of Orally Administered ALS-002158 to Evaluate the Safety, Tolerability and Pharmacokinetics ofSingle Ascending Dosing and Food-effect in Healthy Volunteers, and Multiple Ascending Dosing in Subjects with Chronic Hepatitis C Genotype 1 Infection.
- Conditions
- Chronic Hepatitis C infectionInfection - Other infectious diseasesOral and Gastrointestinal - Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
- Registration Number
- ACTRN12612000176864
- Lead Sponsor
- CPR Pharma Services
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 78
Subjects must meet all of the following criteria to be included in the study:
1. Subject has provided written consent.
2. In the investigator’s opinion, the subject is able to understand and comply with protocol requirements, instructions, and protocol.
3. Subject is in good health as deemed by the investigator, based on the findings of a medical evaluation including medical history, physical examination, laboratory tests,
and ECG.
4. Creatinine Clearance of greater than 50 mL/min (Cockroft-Gault)
5. Male or female, 18–55 years of age for Healthy Volunteers and 18-65 for subjects with CHC.
6. Body mass index (BMI) 18–32 kg/m2 inclusive, minimum weight 50 kg for Healthy Volunteers and 18-36 kg/m2 for subjects with CHC, minimum weight of 50 kg in both populations.
No more than 25% of patients in any cohort may be enrolled with Body mass Index of equal or greater than 30 kg/m2.
7. A female is eligible to participate in this study if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, bilateral
oophorectomy or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea and follicle stimulating hormone (FSH) level within the laboratory’s reference range for postmenopausal females
8. If male, subject is surgically sterile or practicing specific forms of birth control) until 30 days after the end of the study.
In addition, CHC subjects enrolled into the MAD Part (Cohort 1,2 and 3) must also meet the following:
criteria:
1. Positive HCV antibody and a positive HCV RNA at screening.
2. Documentation of CHC infection of greater than 6 months duration at screening.
3. CHC genotype 1 infection at screening.
4. HCV RNA viral load greater than 10to the power of 5 and less than or equal to 10 to the power of 8 IU/mL using a sensitive quantitative assay, e.g., COBAS Taqman- 'Registered Trademark- HCV Test (version 2.0, Roche).
5. Liver biopsy within two years or Fibroscan evaluation within 6 months prior to screening that clearly excludes cirrhosis (Knodell score <3, Metavir score <3, Ishak score <4). Fibroscan liver stiffness score must be <12 kPa.
6. Absence of hepatocellular carcinoma as indicated by an ultrasound scan conducted during screening.
7. No prior treatment for CHC.
8. Absence of history of clinical hepatic decompensation, e.g., variceal bleeding, ascites, hepatic encephalopathy, or active jaundice.
9. Laboratory values including:
prothombin 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 x Upper Limit of Normal
Alpha Fetoprotein concentration = ULN. If AFP is = ULN, absence of a hepatic mass must be demonstrated by ultrasound within the screening period.
Subjects will be ineligible for this study if they meet any one of the following criteria:
1. Clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, thyroid, or any uncontrolled medical illness or psychiatric disorder.
2. Positive test for HAV IgM, HBsAg, HCV Ab (HV only), or HIV Ab.
3. Abnormal screening laboratory results that are considered clinically significant by the investigator.
Liver function tests must all be within normal ranges for healthy volunteers (subjects with documented Gilbert’s disease allowed).
4. Drug allergy such as, but not limited to, sulfonamides and penicillins, including those experienced in previous trials with experimental drugs.
5. Any condition that, in the opinion of the investigator, would compromise the study or the well-being of the subject or prevent the subject from meeting the study
requirements.
6. Participation in an investigational drug trial or having received an investigational vaccine within 30 days or 5 half-lives (whichever is longer) prior receiving to study medication.
7. Clinically significant blood loss or elective blood donation of significant volume (i.e. >500 mL) within 60 days of first dose of study drug; >1 unit of plasma within 7 days of
first dose of study drug.
8. Clinically significant abnormal electrocardiogram (ECG) findings.
9. Pregnant or breast feeding females.
10. Unwilling to abstain from alcohol for 48 hours prior to the start of dosing until collection of the final PK sample during each dosing period.
11. For healthy volunteers, history regular consumption of >7 units of alcohol for females and >14 units per week for males (one unit is defined as 10 g alcohol) within 6 months
of first dose.
12. For healthy volunteers, history of regular use of tobacco-(i.e. greater than or equal to 20 cigarettes per day) or nicotine-containing products within 3 months of the screening visit. For subjects with CHC genotype 1 infection, history of regular use of tobacco- or nicotine-containing products is allowed.
13. The subject has a positive pre-study drug screen. A minimum list of drugs that will be screened for includes amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines.
14. Use of concomitant medications, including vitamins or herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study
medication, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
15. Subjects must not have received any medication known to be an inducer or inhibitor of CYP450 enzymes within 3 weeks prior to clinic check-in. Such medications will continue
to be prohibited until clinic discharge or commencement of CHC treatment.
16. Exposure to more than four new investigational entities within 12 months prior to the first dosing day.
17. Laboratory abnormalities including:
Thyroid Stimulating Hormone (TSH) >ULN
Hematocrit <34 %
White blood cell counts < 3,500/mm3
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method