E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Simvasatins effect on Oxidative Stress |
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E.1.1.1 | Medical condition in easily understood language |
The ability of the body to produced oxidative stress |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10022891 |
E.1.2 | Term | Investigations |
E.1.2 | System Organ Class | 10022891 - Investigations |
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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 |
The scope of the trial is to investigate if simvastatim affecr oxidative stress in helathy volunteers. This will be measured by the biomarkers 8-oxoGuo and 8-oxodG in urine before and after treatment with simvastatin. |
Formålet med studiet er, at undersøge om simvastatin påvirker oxidativt stress i raske, frivillige forsøgsdel-tagere. Dette gøres ved måling af niveauer for biomarkørerne 8‐oxoGuo‐ og 8‐oxodG i urinen før og efter behandling. |
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E.2.2 | Secondary objectives of the trial |
Biomarkers malone dialdehyde, vitamine C, vitamine E and Biopterine is measured in plasma before and after treatment. This is compaired with placebo treatment. |
Niveauer for biomarkørerne Malondialdehyd, Vitamin C, Vitamin E og Biopterine måles i plas-ma før og efter behandling. Dette sammenlignes med en placebo gruppe.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inc-1: caucasian Inc-2: healthy male Inc-3: between 18 and 50 of age Inc-4: BMI between 18 and 30kg/m2 |
Ink‐1. Kaukasiere Ink‐2. Raske mænd Ink‐3. 18 år ≤ alder ≤ 50 år Ink-4. 18 kg/m2 ≤ BMI ≤ 30kg/m2 |
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E.4 | Principal exclusion criteria |
Ex-1: Total cholesterol less than 3 mmol/L
Ex-2: Use of natural and herbal medicines that is affected/affects simvastatin: anionbyttere, amiodaron, amlodipin, ciclosporin, clarithromycin, colchin, danazol, diltiazem, erythromycin, fibrater, fluconazol, fusidine acid, grape fruitjuice, HIV protease inhibotors, itraconazol, ketoconazol, nefazodon, nicotinsyre (niacin), posaconazol, rifampicin, telithromycin, verpamil, vitamin K-antagonists, voriconazol
Ex-3 following diseases: a Coronary vascular disease b Renal insufficiency c Hepatic insufficiency d heart failure e Previous heart arytmia f Hypokalimia g Low blood preassure h hyperthyroidisme i muscular toxicity j galactose intolerens k Lapp LActase deficiency l Glucose/galactose‐malabsorption m Psykiatric disorder |
Eks‐1. Lipidprofil - Total kolesterol ≥ 3 mmol/L
Eks‐2. Brug af medicin og naturlægemidler, der påvirker/påvirkes af simvastatin: anionbyttere, amiodaron, amlodipin, ciclosporin, clarithromycin, colchin, danazol, diltiazem, eryt-hromycin, fibrater, fluconazol, fusidinsyre, grapefrugtjuice, HIV proteasehæmmere, itraconazol, ke-toconazol, nefazodon, nicotinsyre (niacin), posaconazol, rifampicin, telithromycin, verpamil, vitamin K-antagonister, voriconazol
Eks‐3. Følgende lidelser: a. Koronar kredsløbssygdom b. Svær nyreinsufficiens (defineret som Cpl creatinin > 0.100mmol/L) c. Leverinsufficiens (ASAT > 45U/l eller ALAT > 70U/l) d. Svær hjerteinsufficiens e. Tidligere hjertearytmi f. Ikke‐kompenseret hypokaliæmi (defineret som Cpl(K) < 3,5 mmol/L) g. For lavt blodtryk h. Kendt hyperthyroidisme i. Fortilfælde af muskulær toksicitet forsaget af et statin eller fibrat j. Arvelig galactoseintolerans k. Særlig form for heridær lactasemangel (Lapp Lactase deficiency) l. Glucose/galactose‐malabsorption m. Psykisk lidelse
Eks‐4. Indtagelse af narkotiske stoffer op til 2 måneder før screeningsbesøget
Eks‐5. Indtagelse af kosttilskud op til 1 måned før screeningsbesøget
Eks-6. Overfølsomhed overfor simvastatin og/eller andre indholdsstoffer
Eks-7. Samtidig deltagelse i andet klinisk lægemiddelforsøg
Eks-8. Forsøgsdeltager vurderes non-complient.
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E.5 End points |
E.5.1 | Primary end point(s) |
The effect on oxidative stress will be established by comparing the excretion of the biomarkers 8-oxoGuo and 8-oxodG before and after treatment with simvastatin. The result will be compared with the results from the placebo treatment. |
Påvirkningen af oxidativt stress påvises ved at sammenligne udskillelsen af biomarkørerne 8‐oxoGuo og 8‐oxodG før og efter behandling med simvastatin. Resultatet sammenholdes med resultatet fra placebogruppen. Det primære endpoint er niveauet af af 8‐oxoGuo og 8‐oxodG efter behandling med simvastatin i forhold til placebobehandling. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation will e after last patient last visit |
Analysen vil ske efter sidste forsøgsdeltagers sidste besøg |
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E.5.2 | Secondary end point(s) |
The effect on oxidative stress will be established by comparing the excretion of the biomarkers Malone dialdehyde (MDA), Vitamine C (Vit-C), Vitamine E (Vit-E) and Biopterine (BH, as BH4 and BH2) before and after treatment with simvastatin. The result will be compared with the results from the placebo treatment.
MDA: the secondary object is a significant decrease of MDA in plasma after treatment with simvastatin compared to placebo Vit-C: the secondary object is a significant increase of vitamine C in plasma after treatment with simvastatin compared to placebo Vit-E: the secondary object is a significant increase of vitamine E in plasma after treatment with simvastatin compared to placebo BH: the secondary object is a significant increase of BH-4 in plasma after treatment with simvastatin compared to placebo and an increase in BH-4/BH-2 ratio |
Påvirkningen af oxidativt stress påvises ved at sammenligne udskillelsen af følgende biomarkører i plasma før og efter behandling med simvastatin; Malondialdehyd (MDA), Vitamin C (Vit-C), Vitamin E (Vit-E) og Biopterin (BH, henholdsvis tetrahydrobiopterin (BH-4) og dihydrobiopterin (BH-2)). Resultatet sammenholdes med resultatet fra placebogruppen
MDA: Det sekundære endpoint er et signifikant fald i niveau af Malondialdehyd i plasma efter behandling med simvastatin i forhold til placebobehandling. Vit-C: Det sekundære endpoint er et signifikant forøget niveau af Vitamin C i plasma efter behandling med simvastatin i forhold til placebobehandling. Vit-E: Det sekundære endpoint er et signifikant forøget niveau af Vitamin E i plasma efter behandling med simvastatin i forhold til placebobehandling. BH: Det sekundære endpoint er et signifikant forøget niveau af BH-4 i plasma efter behandling med simva-statin i forhold til placebobehandling og forøget BH-4/BH-2 ratio. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation will be after last volunteers last visit |
Analysen vil ske efter sidste forsøgsdeltagers sidste besøg |
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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 | No |
E.6.4 | Safety | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
New mechanisms for simvastatin |
Ny virkningsmekanisme for simvastatin |
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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 | 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 | 2 |
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
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Last volunteer last visit |
Sidste forsøgsdeltagers sidste besøg |
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |