E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the bioequivalence of SOF/VEL as a crushed (test) tablet compared to a whole (reference) tablet in patients treated with SOF/VEL. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of crushed Epclusa tablets in patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with SOF/VEL treatment for the treatment of chronic HCV genotype 1 through 6.
2. Patient is at least 18 at the day of screening.
3. Patient is able and willing to sign the Informed Consent Form.
4. Patient is able and willing to follow protocol requirements.
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E.4 | Principal exclusion criteria |
1. Pregnant female (as confirmed by an hCG test performed 4 weeks before Day 84) or breast-feeding female.
2. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
3. Inability to understand the nature and extent of the study and the procedures required.
4. Clinically relevant low hemoglobin concentration at screening judged by the patient’s own physician
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E.5 End points |
E.5.1 | Primary end point(s) |
Geometric Mean Ratios and the 90% CI interval of the pharmacokinetic parameters (AUC0-tau, Cmax,ss and Ctrough) and median of t½ and tmax,ss of sofosbuvir, GS-331007 and velpatasvir of a crushed tablet (intervention) compared to a whole tablet (reference).
AUC0-24 and Cmax,ss GMR with a 90% CI falling entirely within the range of 0.8 to 1.25 are considered bioequivalent.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetic (PK) curves will be recorded for sofosbuvir and velpatasvir. The curve will be recorded after administration of a whole tablet and a crushed tablet. |
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E.5.2 | Secondary end point(s) |
To evaluate the safety and tolerability of crushed SOF/VEL tablets in patients.
Adverse events after administration of (crushed) SOF/VEL will be described and compared (including clinically relevant laboratory abnormalities).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety assessment on every study visit. Evaluation at the end of the trial. |
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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 | No |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
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) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Intrasubject comparison of PK parameters after different administrations of Epclusa |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
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E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |