E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C virus infection |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019744 |
E.1.2 | Term | Hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of this study are as follows:
To evaluate the relative bioavailability of a pediatric granules formulation of LDV/SOF relative to tablet formulation in healthy subjects.
To evaluate the effect of concomitant food intake on the pharmacokinetics of a pediatric granules formulation LDV/SOF.
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is as follows:
To evaluate the safety and tolerability of a pediatric granules formulation of LDV/SOF following single-dose administration in healthy subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
1. Have the ability to understand and sign a written informed consent form (ICF),
2. Be between 18 and 45 years of age, inclusive
3. Must have a calculated BMI between ≥19.0 to ≤30.0 kg/m2 at Screening
4. Creatinine clearance (CLCr) must be ≥90 mL/min
5. Females of childbearing potential (as defined in Appendix 3) must have a negative serum pregnancy test at Screening and Day -1
6. Females of childbearing potential must agree to utilize protocol recommended highly effective contraception methods (as defined in Appendix 3) from 3 weeks prior to clinic admission until 30 days following the last dose of study drug
7. Male subjects must agree to utilize a highly effective method of contraception (as defined in Appendix 3) during heterosexual intercourse from clinic admission until 90 days following the last dose of study drug.
8. Male subjects must agree to refrain from sperm donation from Day -1 until at least 90 days after the study drug dose
9. Subjects must have refrained from blood donation within 56 days or plasma donation within 7 days of study dosing and from clinic admission until 30 days following the last dose of study drug
10. In the opinion of the investigator, subjects must be in good health based upon medical history and physical examination (including vital signs)
11. Screening laboratory evaluations without clinically significant abnormalities as assessed by the investigator
12. Be willing and able to comply with all study requirements |
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1. Alcohol or substance abuse as assessed by the investigator
2. A positive screening test result for human immunodeficiency virus type 1 (HIV-1) antibody, Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody
3. Nursing female
4. Have previously been participated in an investigational trial involving administration of any investigational compound (last dose) within 30 days prior to the study dosing (Day 1)
5. Have poor venous access limiting phlebotomy
6. Have been vaccinated within 90 days, or for the influenza vaccine, within 14 days prior to study dosing
7. Have taken any prescription medications or over-the-counter medications including herbal products within 28 days of commencing study drug dosing with the exception of vitamins and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications
8. Have taken systemic steroids, immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening or expected to receive these agents during the study
9. Have a history of any of the following:
a. Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)
b. Significant serious skin disease, such as but not limited to, rash or eruptions, food allergy, eczema, psoriasis, or urticaria
c. Known hypersensitivity to the study drugs, the metabolites or to formulation excipients (see Section 5.2.1)
d. Syncope, palpitations, or unexplained dizziness
e. Liver disease or liver function tests such as alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), serum total bilirubin, or alkaline phosphatase above the upper limit of normal at Screening
f. Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions requiring prolonged (> 6 months) medical treatment
g. Medical or surgical treatment that permanently alters gastric absorption (eg, gastric or intestinal surgery)
h. Significant cardiac disease (including history of myocardial infarction based on electrocardiogram [ECG] and/or clinical history, any history of ventricular tachycardia, congestive heart failure, or dilated cardiomyopathy with left ventricular ejection fraction < 40%) or a family history of Long QT Syndrome
10. The following ECG abnormalities at Screening: QRS > 120 msec; heart rate < 45 beats per minute; second or third degree heart block, QTcF interval > 450 msec for males or > 470 msec for females; PR interval > 200 msec and any other clinically relevant abnormality
11. Believed, by the study investigator, to be inappropriate for study participation for any reasond. Syncope, palpitations, or unexplained dizziness
e. Liver disease or liver function tests such as alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT), aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT), serum total bilirubin, or alkaline phosphatase above the upper limit of normal at Screening
f. Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions requiring prolonged (> 6 months) medical treatment
g. Medical or surgical treatment that permanently alters gastric absorption (eg, gastric or intestinal surgery)
h. Significant cardiac disease (including history of myocardial infarction based on electrocardiogram [ECG] and/or clinical history, any history of ventricular tachycardia, congestive heart failure, or dilated cardiomyopathy with left ventricular ejection fraction < 40%) or a family history of Long QT Syndrome
10. The following ECG abnormalities at Screening: QRS > 120 msec; heart rate < 45 beats per minute; second or third degree heart block, QTcF interval > 450 msec for males or > 470 msec for females; PR interval > 200 msec and any other clinically relevant abnormality
11. Believed, by the study investigator, to be inappropriate for study participation for any reason |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are PK parameters Cmax, AUClast, and AUCinf, for SOF, GS-566500, GS-331007, and LDV. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Scheduled assessment points throughout the treatment period |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are the incidences of AEs, laboratory abnormalities and vital signs.
The secondary PK endpoints are % AUCexp, Tmax, Clast, Tlast, λz, CL/F, and t1/2 as appropriate. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Scheduled assessment points throughout the treatment period |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | Yes |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 31 |