E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cystic fibrosis in patients homozygous for the F508del-CFTR Mutation |
Patienten met Cystische Fibrose die homozygoot zijn voor de F508del-CFTR Mutatie |
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E.1.1.1 | Medical condition in easily understood language |
Cystic fibrosis |
Cystische Fibrose |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of lumacaftor in combination with ivacaftor
through Week 24 in subjects with Cystic Fibrosis (CF) who are
homozygous for the F508del mutation on the CF transmembrance
conductance regulator (CFTR) gene. |
De effectiviteit te evalueren van lumacaftor in combinatiemet ivacaftor tot en met week 24 bij deelnemers met CF die homozygoot zijn voor de F508del mutatie op het CF transmembraan condutance regulator gen (CFTR)
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of lumacaftor in combination with ivacaftor through Week 24
To investigate the pharmacokinetics (PK) of lumacaftor and its metabolite, M28 (M28 lumacaftor) and ivacaftor and its metabolites M1 and M6 (M1 ivacaftor and M6 ivacaftor) |
Om de veiligheid te evalueren van lumacaftor in combinatie met ivacaftor tot en met week 24
Om de farmacokinetiek (PK) van lumacaftor en zijn metaboliet, M28 onderzoeken (M28-lumacaftor) en ivacaftor en de metabolieten, M1 en M6 (M1-ivacaftor en
M6-ivacaftor) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males and females, aged 12 years or older on the date of informed consent or, where appropriate, date of assent
• Confirmed diagnosis of CF
• Homozygous for the F508del CFTR mutation
• FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
• Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit
|
Mannen en vrouwen in de leeftijd van 12 jaar of ouder op de dag van geïnformeerde toestemming of, indien van toepassing de datum van instemming.
Bevestigde diagnose van CF.
Homozygoot zijn voor de F508del-CFTR mutatie.
FEV1 ≥ 40% en ≤ 90% van de voorspelde normaal waarden mbt leeftijd, geslacht, en hoogte (Hankinson of Wang vergelijkingen) bij de screening (zie paragraaf 12.7.1). t/m week 24
Bereid om op stabiele CF medicatie te blijven staan tot en met week 24, of, indien van toepassing, tot aan het vervolg bezoek. |
|
E.4 | Principal exclusion criteria |
• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before first dose of study drug
• History of solid organ or hematological transplantation
• History of alcohol or drug abuse in the past year
• Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening
• Use of strong inhibitors, moderate inducers or strong inducers of CYP3A, including consumption of certain herbal medications (e.g., St. John's Wort) and certain fruit and fruit juices within 14 days before Day 1 of dosing |
Een acute bovenste of onderste luchtweginfectie, pulmonale exacerbatie, of veranderingen in de therapie (waaronder antibiotica) voor longziekten binnen 4 weken voor de eerste dag van studiemedicatie inname.
Orgaan-of hematologische transplantatie in het verleden
Geschiedenis van alcohol-of drugsmisbruik in het afgelopen jaar, met inbegrip van maar niet beperkt tot cannabis,cocaïne en opiaten naar oordeel van de onderzoeker.
Huidige of eerdere deelname aan een geneesmiddel onderzoek (waaronder studies met lumacaftor en / of ivacaftor) binnen 30 dagen voor screening.
Het gebruik van een sterke remmers, gemiddelde inductoren of sterke inductoren van CYP3A, met inbegrip van de consumptie van bepaalde kruiden medicatie (bijvoorbeeld, St Janskruid) en bepaalde fruit en vruchtensappen binnen 14 dagen voor de eerste dag van inname van studiemedicatiezie paragraaf 10.3.
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline at Week 24 |
Absolute percentuele verandering in voorspelde geforceerd expiratoire volume binnen 1 seconde (FEV1) van baseline op week 24. |
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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) |
Relative change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline at Week 24
Absolute change in body mass index (BMI) from baseline at Week 24
Number of pulmonary exacerbations from baseline through Week 24
Absolute change in Cystic Fibrosis Questionnaire – Revised (CFQ-R) respiratory domain score from baseline at Week 24
Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values (hematology, serum chemistry, coagulation studies, and urinalysis), standard digital electrocardiograms (ECGs), pulse oximetry and vital signs |
Relatieve percentuele verandering in voorspelde geforceerd expiratoire volume binnen 1 seconde (FEV1) van baseline op week 24.
Absolute verandering in de body mass index (BMI) vanaf baseline op week 24
Aantal pulmonale exacerbaties tot en met week 24
Absolute verandering in Cystic Fibrosis Questionnaire-Revised (CFQ-R) score van baseline op week 24
Veiligheid en verdraagbaarheids beoordelingen op basis van bijwerkingen (AE's), klinische standaard laboratorium waarden (hematologie, serum chemie, coagulatie studies, en urineonderzoek) elektrocardiogrammen (ECG's), ambulante ECG's, vitale functies en pulsoximetrie
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 24 and 28 |
Week 24 en 28 |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Czech Republic |
France |
Germany |
Ireland |
Italy |
Netherlands |
Sweden |
United Kingdom |
United States |
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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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LVLS Last Visit Last Subject 31-07-2014 |
laatste visite laatste deelnemer 31-07-2014 |
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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 | 3 |
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 | 3 |