E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hypercholesterolemia |
hypercholesterolémie |
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E.1.1.1 | Medical condition in easily understood language |
high cholesterol in blood |
vysoký cholesterol v krvi |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020604 |
E.1.2 | Term | Hypercholesterolemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 determine whether response of cholesterol concentration and concentration of 7alpha-hydroxycholest-3-en-4-one (C4) to treatment with bile acid sequestrant differ between homozygous carriers of -203C allele and homozygous carriers of -203A allele of cholesterol 7alpha-hydroxylase gene (CYP7A1)
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Zjistit, zda se liší odpověď cholesterolémie a koncentrace 7alfa-hydroxycholest-3-en-4-onu (C4) na podání sekvestrantu žlučových kyselin mezi osobami homozygotními pro variantu -203A a osobami homozygotními pro variantu -203C v genu pro cholesterol-7alfa-hydroxylasu (CYP7A1).
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E.2.2 | Secondary objectives of the trial |
To determine whether treatment with bile acid sequestrant has a positive effect on selected parameters of insulin sensitivity. |
Zjistit, zda léčba sekvestrant žlučových kyselin příznivě ovlivňuje vybrané parametry inzulínové senzitivity. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-study in healthy volunteers:
Aim of the sub-study is to determine the dynamics of response of cholesterol concentration and concentration of 7alpha-hydroxycholest-3-en-4-one (C4) to treatment with bile acid sequestrant in homozygous carriers of -203C allele and homozygous carriers of -203A allele of cholesterol 7alpha-hydroxylase gene (CYP7A1).
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Studie u zdravých dobrovolníků:
Cílem této studie je určit dynamiku odpovědi cholesterolémie a koncentrace 7alfa-hydroxycholest-3-en-4-onu (C4) na podání sekvestrantu žlučových kyselin u osob homozygotních pro variantu -203A a osob homozygotních pro variantu -203C v genu pro cholesterol-7alfa-hydroxylasu (CYP7A1).
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E.3 | Principal inclusion criteria |
Patients:
- sex: males and females
- age: 18 - 65 years
- confirmation of contraception used (in fertile women)
- LDL-cholesterol (calculated) > 3 mmol/l
- homozygote for -203A or -203C allele of CYP7A1 gene
Sub-study in healthy volunteers:
- sex: males
- age: 18 - 65 years
- BMI < 30 kg/m2
- total cholesterol > 5 mmol/l
- homozygote for -203A or -203C allele of CYP7A1 gene |
Pacienti:
- pohlaví: muži i ženy
- věk 18 - 65 let
- u žen ve fertilním věku potvrzení o používané antikoncepci
- LDL-cholesterol (stanovený výpočtem) > 3 mmol/l
- homozygot pro variantu -203A nebo -203C genu CYP7A1
Studie u zdravých dobrovolníků:
- pohlaví: muž
- věk 18 - 65 let
- BMI < 30 kg/m2
- celkový cholesterol > 5 mmol/l
- homozygot pro variantu -203A nebo -203C genu CYP7A1 |
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E.4 | Principal exclusion criteria |
Patients:
- triglyceride > 3 mmol/l
- pregnancy, breast-feeding
- treatment with hypolipidemic drugs and oral anticoagulants
- decompensated diabetes mellitus
- insulin treatment
- serious thyreopathy
- presence of another confirmed serious disease that could endanger or disadvantage the patient if included into the trial
- hypersensitivity to colesevelam or any of the excipients
- intestine or bile duct obstruction, obstipation
Sub-study in healthy volunteers:
- triglyceride > 3 mmol/l
- presence of confirmed serious disease such as ischemic heart disease, diabetes mellitus, thyreopathy, nephrotic syndrome, dysproteinemia and others that could endanger or disadvantage the subject if included into the trial
- alcoholism
- mental disorders
- hypersensitivity to colesevelam or any of the excipients
- intestine or bile duct obstruction, obstipation |
Pacienti:
- triglyceridy > 3 mmol/l
- gravidita, kojící ženy
- léčba hypolipidemiky, perorálními antikoagulancii
- dekompenzovaný diabetes mellitus
- léčba inzulinem
- závažná thyreopathie
- přítomnost potvrzeného závažného onemocnění, které by mohlo podle mínění zkoušejícího ohrozit nebo znevýhodnit pacienta v případě, že by se klinického hodnocení zúčastnil
- hypersenzitivita na léčivou látku nebo na kteroukoli pomocnou látku přípravku
- obstrukce střeva nebo žlučových cest, obstipace
Zdraví dobrovolníci:
- triglyceridy > 3 mmol/l
- přítomnost potvrzeného závažného onemocnění jako např. ischemické choroby srdeční, diabetu mellitus, thyreopathie, nefrotického syndromu, dysproteinémie, a dalších, které by mohly podle mínění zkoušejícího ohrozit nebo znevýhodnit pacienta v případě, že by se klinického hodnocení zúčastnil
- alkoholismus
- psychické poruchy
- hypersenzitivita na léčivou látku nebo na kteroukoli pomocnou látku přípravku
- obstrukce střeva nebo žlučových cest, obstipace
va nebo žlučových cest), obstipace
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E.5 End points |
E.5.1 | Primary end point(s) |
Patients:
1. difference in change of cholesterol and LDL-cholesterol concentrations between homozygous carriers of -203C and -203A alleles of CYP7A1 gene after 28 days of therapy
2. difference in change of 7alpha-hydroxycholest-3-en-4-one (C4)concentration between homozygous carriers of -203C and -203A alleles of CYP7A1 gene after 28 days of therapy
Sub-study in healthy volunteers:
1. difference in dynamics of change of cholesterol and LDL-cholesterol concentrations between homozygous carriers of -203C and -203A alleles of CYP7A1 gene during 28 days of therapy
2. difference in dynamics of change of 7alpha-hydroxycholest-3-en-4-one (C4) concentration between homozygous carriers of -203C and -203A alleles of CYP7A1 gene of CYP7A1 gene during 28 days of therapy |
Pacienti:
1. rozdíl ve změně cholesterolémie a koncentrace LDL-cholesterolu mezi homozygotními nositely variant -203C a -203A v genu CYP7A1 po 28 dnech léčby
2. rozdíl ve změně koncentrace 7alfa-hydroxycholest-3-en-4-onu (C4)mezi homozygotními nositely variant -203C a -203A v genu CYP7A1 po 28 dnech léčby
Studie u zdravých dobrovolníků:
1. rozdíl v dynamice změny cholesterolémie a koncentrace LDL-cholesterolu mezi homozygotními nositely variant -203C a -203A v genu CYP7A1 v průběhu 28 dnů léčby
2. rozdíl v dynamice změny koncentrace 7alfa-hydroxycholest-3-en-4-onu (C4) mezi homozygotními nositely variant -203C a -203A v genu CYP7A1 v průběhu 28 dnů léčby |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients:
Day 1 - baseline
Day 29 - after 28 days of therapy
Sub-study in healthy volunteers:
Day 1 - baseline
Day 2 - after 1 day of therapy
Day 4 - after 3 days of therapy
Day 8 - after 7 days of therapy
Day 15 - after 14 days of therapy
Day 29 - after 28 days of therapy |
Patients:
Den 1 - pře léčbou
Den 29 - po 28 dnech léčby
Studie u zdravých dobrovolníků:
Den 1 - před léčbou
Den 2 - po 1 dnu léčby
Den 4 - po 3 dnech léčby
Den 8 - po 7 dnech léčby
Den 15 - po 14 dnech léčby
Den 29 - po 28 dnech léčby |
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E.5.2 | Secondary end point(s) |
Change in concentration of selected biochemical parametres reflecting insulin sensitivity: insulin, glucose, GLP-1, leptin, adiponectin + HOMA index (insulin*glucose/22.5) |
Změna koncentrace vybraných biochemických parametrů, které umožňují posoudit inzulínovou senzitivitu: inzulín, glukóza, GLP-1, leptin, adiponektin + HOMA index (inzulín*glukóza/22,5) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patients:
Day 1 - baseline
Day 29 - after 28 days of therapy
Sub-study in healthy volunteers:
Day 1 - baseline
Day 2 - after 1 day of therapy
Day 4 - after 3 days of therapy
Day 8 - after 7 days of therapy
Day 15 - after 14 days of therapy
Day 29 - after 28 days of therapy |
Patients:
Den 1 - pře léčbou
Den 29 - po 28 dnech léčby
Studie u zdravých dobrovolníků:
Den 1 - před léčbou
Den 2 - po 1 dnu léčby
Den 4 - po 3 dnech léčby
Den 8 - po 7 dnech léčby
Den 15 - po 14 dnech léčby
Den 29 - po 28 dnech léčby |
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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 | No |
E.6.5 | Efficacy | Yes |
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 | 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 | 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 | Yes |
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 |
Poslední kontrola posledního ze subjektů klin. hodnocení |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |