A Study in Healthy Subjects to Evaluate Pharmacokinetics and Food Effect After Dosing of GS-248
Condition: Pharmacokinetic
Intervention: Formulation A GS-248; Formulation B GS-248
Intervention description: Formulation A of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg.; Formulation B of GS-248 in a capsule, dose 120 mg given as a single-dose of 3 capsules a´40 mg.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: The study is divided in two parts. Part I will evaluate PK, safety and tolerability of a single oral dose of two different formulations of GS-248 in fasting conditions. Part II will evaluate PK, safety and tolerability of one of the two different formulations of GS-248 in fed conditions. Subjects are expected to participate in both Part I and Part II.
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pharmacokinetic

Summary:

      The study will collect information about pharmacokinetics (PK), safety and tolerability
      following a single dose of GS-248 in two different oral solid formulations in capsules to
      healthy subjects. It will also collect information about pharmacokinetics (PK), safety and
      tolerability following a single dose of one of the two formulations of GS-248 in fed
      condition.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Willing and able to give written informed consent for participation in the study.

          2. Healthy male or female subject aged ≥ 18 and ≤70 years.

          3. Body Mass Index (BMI) ≥ 19.0 and ≤ 30.0 kg/m2.

          4. Clinically normal medical history, physical findings, vital signs, ECG and laboratory
             values at the time of screening, as judged by the Investigator.

          5. Women of child bearing potential (WOCBP) must practice abstinence from heterosexual
             intercourse (only allowed when this is the preferred and usual lifestyle of the
             subject) or must agree to use a highly effective method of contraception with a
             failure rate of < 1% to prevent pregnancy (combined [oestrogen and progestogen
             containing] hormonal contraception [oral, intravaginal, transdermal], progestogen-only
             hormonal contraception associated with inhibition of ovulation [oral, injectable,
             implantable], intrauterine device [IUD]or intrauterine hormone-releasing system [IUS])
             from at least 4 weeks prior to dose to 4 weeks after last dose.

        Exclusion Criteria:

          1. Known allergy to GS-248.

          2. Females who are breast feeding or who plan to become pregnant until 2 weeks after the
             end-of-study visit.

          3. Positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent
             units of human chorionic gonadotropin [HCG]) at screening and within 24 h prior to the
             first administration of IMP.

          4. Regular use of corticosteroids (inhaled and systemic), NSAIDs, aspirin or coxibs,
             antacids, PPIs, or any other medication that changes gastric pH within 14 days of
             study drug administration.

          5. Regular use of any prescribed or non-prescribed medication including analgesics,
             herbal remedies, vitamins and minerals within 2 weeks prior to the (first)
             administration of IMP, except hormonal contraception and occasional intake of
             paracetamol (maximum 2000 mg/day; and not exceeding 3000 mg/week) and nasal
             decongestants without cortisone, antihistamine or anticholinergics for a maximum of 10
             days, at the discretion of the Investigator.

          6. Presence of inherited or acquired disorders of platelet function, bleeding or
             coagulation, as judged by the investigator.

          7. History or presence of any clinically significant disease or disorder which, in the
             opinion of the Investigator, may either put the subject at risk because of
             participation in the study, or influence the results or the subject's ability to
             participate in the study.

          8. After 10 minutes supine rest at the time of screening, any vital signs values outside
             the following ranges:

               -  Systolic blood pressure <90 or >140 mmHg, or

               -  Diastolic blood pressure <50 or >90 mmHg, or

               -  Pulse <40 or >90 bpm

          9. Positive test for serum hepatitis B surface antigen (HBsAg), hepatitis C virus
             antibodies (HCVAb) or HIV 1 and/or 2 antibodies at screening.

         10. Presence or history of drug and/or alcohol abuse and/or excessive intake of alcohol
             and/or history, or current use, of anabolic steroids, as judged by the Investigator.

         11. Positive test for drugs of abuse or alcohol at screening or on admission to the unit
             prior to administration of the IMP.

         12. Participation in other interventional studies within 3 months prior to administration
             of study drug.

         13. Consumption of grapefruit, grapefruit juice, other grapefruit-containing products, or
             Seville oranges within 14 days of first IMP administration.

         14. Any clinically significant illness, medical/surgical procedure or trauma within 4
             weeks of the first administration of IMP.

         15. Malignancy within the past 5 years with the exception of in situ removal of basal cell
             carcinoma.

         16. Any planned major surgery within the duration of the study.

         17. Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant
             abnormalities in the resting ECG, as judged by the Investigator.

         18. Current smokers or users of nicotine products. Irregular use of nicotine (e.g.,
             smoking, snuffing, chewing tobacco) less than three times per week is allowed before
             screening visit.

         19. Regular excessive caffeine consumption defined by a daily intake of >5 cups of
             caffeine-containing beverages.

         20. Intake of xanthine- and/or taurine-containing energy drinks within 2 days prior to
             screening and prior to IMP administration.

         21. Plasma donation within one month of screening or blood donation (or corresponding
             blood loss) during three months prior to screening.

         22. Investigator considers the subject unlikely to comply with study procedures,
             restrictions and requirements.

         23. Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m2 (determined by the
             revised Lund-Malmö GFR estimating equation).

         24. Subjects with swallowing disorders, which may affect the subject´s capability to
             swallow the IMP.

         25. Subjects who are vegetarian or for other reasons cannot eat the high-fat high-calorie
             breakfast.