E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronary heart disease patients With perceived statin Associated muscle symptoms or statin discontinuaton due to muscle symptoms |
|
E.1.1.1 | Medical condition in easily understood language |
Coronary heart disease patients who report muscle symptoms during treatment with atorvastatin or who have stopped taking their atorvastatin pill due to muscle symptoms |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 primary objective is to estimate the effect of atorvastatin on muscular symptom intensity in coronary patients with subjective statin associated muscle symptoms (SAMS).
|
|
E.2.2 | Secondary objectives of the trial |
The key secondary objectives are: • To determine the relationship between confirmed SAMS and blood concentrations of parent drug and the active metabolites of atorvastatin and SAMS in patients with confirmed SAMS • To determine the proportion of patients who report muscle symptoms on atorvastatin treatment and not on placebo (dichotomous SAMS classification) • To determine mean difference in the likelihood of statin discontinuation within and between the treatment periods • To characterize features ofcompare patients with and without confirmed SAMS and in the total sampleregarding muscle symptom charcteristics • To study statin adherence between the two study arms • To study sociodemographic, clinical, and psychosocial characteristics (PROMS and clinical data) between the two study arms
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• First or recurrent diagnosis (myocardial infarction) or treatments (PCI or CABG) for a CHD event 6-36 months prior to study start and prescribed atorvastatin. • Self-reported muscle complaints (i.e. pain, weakness, tenderness, stiffness or cramp to the body of any intensity) that they attribute to atorvastatin therapy at study inclusion • Self-reported muscle complaints that has led to atorvastatin discontinuation at study inclusion.
|
|
E.4 | Principal exclusion criteria |
• First or recurrent diagnosis (myocardial infarction) or treatments (PCI or CABG) for a CHD event the past 12 months prior to study start in high risk patients (i.e. at least one of following comorbid conditions: systolic heart failure, >1 previous myocardial infarction, kidney failure, diabetes, and smokers) • First or recurrent diagnosis (myocardial infarction) or treatments (PCI or CABG) for a CHD event the past 6 months prior to study start in low risk patients without any of the co-morbid conditions mentioned above and in patients who are not taking a statin at all • Patients with residual stenosis on the major coronary arteries that were not revascularized at the time of the index event, patents with symptomatic peripheral artery disease and patients with familial hypercholesterolemia • Patient has any contraindications for atorvastatin listed in the Summary of Product Characteristics (i.e. known hypersensitivity to the ingredients, acute liver failure/ ALT > 3 times upper limit of the normal range in blood at study start, pregnancy and breastfeeding ) • History of previous rhabdomyolysis, myopathy or liver failure due to statin treatment with CK > 10 times upper limit of the normal range or ALT > 3 times upper limit of the normal range. • Any condition (e.g. psychiatric illness, dementia) or situation, that in the investigator’s opinion could put the subject at significant risk, confound the study results, interfere significantly with the subject participation in the study, or rendering informed consent unfeasible • Short life expectancy due to other medical conditions • Not being able to understand Norwegian. • Women of childbearing potential defined as a premenopausal female capable of becoming pregnant. • Participation in another randomized clinical trial
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point will be assessed by the individual mean difference in muscular symptom intensity between treatment periods with statin and placebo, reported by the patients over the last three weeks (i.e. week 4-7) measured with aggregated VAS scores |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At study start, during the 7x2 weeks treatment period and at study end |
|
E.5.2 | Secondary end point(s) |
Assessment of the secondary study end-points will be ascertained through self-reported questionnaires, clinical examinations, and blood samples collected at baseline, during the treatment periods, and at study-end : • Levels of atorvastatin and its metabolites in blood plasma and white blood cells. • The proportion of patients who report muscle symptoms on atorvastatin treatment and not on placebo (dichotomous SAMS classification). • Likelihood of statin discontinuation measured on a 1-10 Likert scale. • Features of SAMS characterized by McGill Pain Questionnaire (SF-MPQ) and Brief Pain Inventory (BPI-SF). • Statin adherence measured with indirect (self-reported questionnaires and pill counts of returned packages) and direct (liquid chromatography-tandem mass spectrometry) methods. • Sociodemographic, clinical, and psychosocial factors ascertained through self-reported questionnaires, clinical examinations, and blood samples.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At study start, during the 7x2 weeks treatment period and at study end |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
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
| 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 | 2 |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 19 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 15 |