E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic hepatitis B |
Chronische hepatitis B |
|
E.1.1.1 | Medical condition in easily understood language |
viral liver infection with hepatitis B virus |
virale leverontsteking door het hepatitis B virus |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
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 main objective of this study is to compare the incidence of KPTD in
mildly renally impaired HBV-infected persons on TDF to the incidence in
renally sufficient HBV-infected persons on TDF. |
Het primaire doel van deze studie is om de incidentie van KPTD vast te
stellen bij chronisch HBV-geïnfecteerde TDF-gebruikers met normale
nierfunctie (eGFR > 80ml/min) en met mild nierfunctieverlies (eGFR 50-
80 ml/min). |
|
E.2.2 | Secondary objectives of the trial |
Secondary goals are to relate tenofovir plasma, intracellular and urine
levels to the incidence of KPTD, to evaluate the incidence of KPTD in the
first year of treatment and to evaluate bone demineralisation in the first
year of treatment in mildly renally impaired HBV-infected persons on
TDF and in renally sufficient HBV-infected persons on TDF. |
Secundaire doelen zijn om plasma tenofovir, intracellulair tenofovirdifosfaat
en urine tenofovir waarden vast te stellen voor deze populatie
en om deze te correleren aan het ontstaan van KPTD. Ook wordt
bot(de)mineralisatie voor start van therapie en na 48 weken therapie
vergeleken tussen de 2 studiegroepen. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
Adult (> 18 years old), chronically HBV-infected, meeting the criteria for antiviral therapy
Group 1: 25 persons starting TDF with creatinine clearances between 50-80 mL/min
Group 2: 25 persons starting TDF with creatinine clearances of > 80 mL/min |
Inclusiecriteria:
Volwassen leeftijd (tenminste 18 jaar oud), chronische hepatitis B, indicatie voor antivirale therapie.
Groep 1: 25 personen die starten met TDF met een eGFR 50-80 ml/min.
Groep 2: 25 personen die starten met TDF met een eGFR > 80 ml/min. |
|
E.4 | Principal exclusion criteria |
Exclusion criteria
Renal clearance (CG) < 50 mL/min, HIV- and/or HCV-co infection. |
Exclusiecriteria:
eGFR < 50ml/min, HIV- en/of HCV-infectie. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The occurrence of kidney proximal tubular dysfunction (KPTD).
KPTD is defined as the presence of at least two of the following; a decreased renal threshold phosphate concentration (TmP/GFR < 0.80 mmol/L), any normoglycemic (<10 mmol/L) glycosuria,
hyperaminoaciduria, hyper β2-microglobulinuria (normal < 400 μg/L), increased retinol binding protein loss (normal < 0.017 mg RBP/mmol creatinine), hyperuricosuria (normal < 5 mmol/24h). |
Het ontstaan van KPTD
KPTD wordt gedefinieerd als de aanwezigheid van tenminste 2 van de volgende: een verminderde renale fosfaatdrempel (TmP/GFR < 0.80 mmol/L), normoglycemische glucosurie, hyperaminoacidurie, hyperbeta2-microglobulinurie (normaal < 400 ug/L), verhoogde retinol bindend proteïne excretie in de urine (normaal < 0.017 mg RBP/mmol kreatinine), hyperuricosurie (normaal < 5 mmol/24u). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- The values of plasma TFV, urine TFV and intracellular TFV-DP levels in both study groups.
- The relation between plasma TFV, urine TFV and intracellular TFV-DP levels and the occurrence of KPTD.
- The difference in bone mineralisation in the first year of treatment within and between study groups. |
- de waarden van plasma tenofovir (TFV), urine tenofovir (TFV) en intracellulair tenofovir-difosfaat (TFV-DP).
- de relatie tussen plasma tenofovir (TFV), urine tenofovir (TFV) en intracellulair tenofovir-difosfaat (TFV-DP) en KPTD.
- veranderingen in botmineralisatie in het eerste jaar van behandeling binnen en tussen beide groepen. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 4, 12, 24, 36 and 48 weeks after initiation of therapy. |
4, 12, 24, 36 en 48 weken na de start van de therapie. |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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
|
LVLS |
Laatste bezoek van de als laatste geincludeerde patient.
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 0 |