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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019183 |
E.1.2 | Term | HCV |
E.1.2 | System Organ Class | 100000004848 |
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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 evaluate if adequate exposure to ribavirin can be achieved after a dose adjustment based on the AUC0-4h from a first dose of ribavirin. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate how many patients need a dose adjustment to achieve adequate exposure to ribavirin
- To evaluate if there are subgroups of HCV infected patients who more often need a dose adjustment to achieve sufficient exposure to ribavirin
- To evaluate the safety and tolerability of a dose adjustment of ribavirin in (formerly) HCV infected patients
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is at least 18 years at screening.
2. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
3. Subject has been treated with RBV and PEG-IFN for a chronic HCV infection for at least 4 weeks
4. Female subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or female subject is of childbearing potential practicing adequate contraception, e.g. intrauterine device, hormonal contraceptives, sponge, foams, jellies, diaphragm all in combination with condom use by the sexual partner; double barrier method, vasectomized partner, or total abstinence.
They must agree to take precautions in order to prevent a pregnancy throughout the entire study and until four months after the end of this study.
5. Male subject is practicing one of the following methods of birth control during this study with RBV and for seven months after the end of the study: condoms, is vasectomized or total abstinence from sexual intercourse. Next to that, the female sexual partner should practice an adequate contraception method.
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E.4 | Principal exclusion criteria |
1. Inability to understand the nature and extent of the trial and the procedures required.
2. Participation in a drug trial within 60 days prior to the first dose.
3. RBV use within 90 days prior to the first dose.
4. Pregnancy or a pregnant partner (unless subject agrees to use condoms)
5. Breastfeeding
6. Hemoglobinopathies (e.g. thalassemia, sickle-cell anaemia)
7. Severe reaction to ribavirin during previous treatment that makes the subject ineligible for ribavirin use in the opinion of the investigator
8. A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months
9. A history of severe psychiatric condition, particularly severe depression, suicidal ideation or suicide attempt.
10. Hemoglobin (Hb) < 7.5 mmol/L (female) or < 8.5 mmol/L (male)
11. HIV positive patients with CD4-count < 200 cells/mm3 within 3 months prior to screening
12. Creatinine clearance < 50 mL/min
13. Signs of progressive liver disease, such as
• Decompensated cirrhosis (Child-Pugh grade B or C), and/or
• Bilirubin > 35 µmol/L or albumin <38 g/L or PTT >4 sec or platelets < 90 x 109/L |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is the proportion of patients with an AUC0-4h in the target range with the second dose within this study. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• To evaluate how many patients need a dose adjustment to achieve adequate exposure to RBV.
• To evaluate if there are subgroups of HCV infected patients who more often need a dose adjustment to achieve sufficient exposure to RBV.
• To evaluate the safety and tolerability of a dose adjustment of RBV in (formerly) HCV infected patients
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 1 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 2 |