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This study examines Lumacaftor/Ivacaftor (Orkambi) treatment targeting specific mutations in the KCNH2 gene in patients with long QT syndrome type 2 (LQT2). It enrolled patients aged 18-65 who carry class II (trafficking-defect) mutations in the KCNH2 gene. The study was conducted in Phase 2 and has been completed.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
Inclusion Criteria: * Informed consent: it is requested that the partipants understand the nature of the study and can give their voluntary conset after being fully informed, after having received satisfying replies to their questions regarding the study, and all the authorizations according to local requirements. The informed consent form was previously approved by the local Ethics Committee and will have to be dated and signed before enrollment in the study. * Age and gender: participants of both the male and female sex aged between 18 and 65 years will be included * Mutations: the study will enrol patients with LQT2, i.e., with pathogenic mutations on the KCNH2 gene, that present such functional characterization that classifies them as class II mutations, namely mutations that cause a trafficking defect. This characterization includes, but is not limited to, patch clamp data in single cells, immunofluorescence data, positive reactions to drugs that correct the trafficking defect in vitro. * Consent of the patient to not participate in any other clinical study during the entire period of participation in the present study * Women with child-bearing potential (pre-menopausal women, less than two years after start of menopause and women who are not surgically sterile) must use a highly effective contraceptive method from 30 days before enrollment in the study until 28 days after the last administration of study drug. It is specified that the sole use of hormonal contraception, both oral, injectable, transdermic and implantable cannot be considered an effective contraceptive method. Orkambi (Lumacaftor/ivacaftor) may reduce the exposure to the hormonal contraceptives and possibly cause their ineffectiveness. Male patients with a female partner with child-bearing potential must use 2 forms of contraception (one of which should be a double-barrier method) from enrolment in the study until 28 days after the last administration of study drug. Highly effective contraceptive methods are: i) abstinence, ii) surgical sterilization (=6 months postsurgery), iii) intrauterine device or intrauterine system, iv) oral contraceptives combined with a barrier method, v) double-barrier method (e.g., male condom or diaphragm with vaginal spermicides). Exclusion Criteria: * Absence of one or more of the preceeding inclusion criteria * Hypersensitivity to the active substance (to one or both active substances) or to one of the excipients. * Pregnancy (established before enrollment by positive urine pregnancy test in potentially fertile women) or breastfeeding * Participation in a clinical study in which an experimental drugs has been administered less than 30 days or less than 5 half-lives before the present study drug * Any clinical condition that in the opinion of the investigator causes the patients not to be suitable for the study and/or that may involve an unreasonable/significant risk for the participants, thereby changing the interpretation of that data and affecting the continuation of the study * Other important cardiac diseases and in particular: cardiomyopathies and myocarditis, pericardial diseases, other associated channelopathies, ischemic heart disease, heart failure, pulmonary heart disease, severe valuvulopathies, rhythm alterations such as atrial fibrillation or atrial flutter, complete right or left bundle branch block, advanced atrio-ventricular blocks, uncontrolled arterial hypertension on beta-blocker therapy * Significant extracardiac diseases and in particular: * renal failure. In accordance with the SmPC, patients with severe (estimated GFR \<30 mL/min/1.73 m2) and moderate (estimated GFR 30-60 mL/min/1.73 m2) renal impairment at screening are excluded * impairment of liver function. In accordance with the SmPC, patients with severe (Child-Pugh Class C) and moderate (Child-Pugh Classe B) liver function impairment are excluded * important diseases of the respiratory system and in particular: any pulmonitis, obstructive bronchopulmonary disease with FEV1 \<80%, asthmatic bronchitis, infiltrative lung disease, lung emboly, pulmonary hypertension, idiopathic pulmonary fibrosis, pneumothorax, neoplasms of lungs and pleura * important neurological diseases and in particular: epilepsy, cerebral hemorrhage, stroke, multiple sclerosis, cerebral tumours, cerebral or spinal traumas, Parkinson's disease, cognitive deterioration and Alzheimer's disease * Chronic use of therapies other than beta-blocker treatment and intake of any potassium/magnesium supplement that the patient may use chronically or intermittently (oral contraceptives are allowed, but must be interrupted during the study).