Clinical trial NCT03696940: Clinical Trial to Evaluate the Efficacy of a Dyslipidemic Therapy in Mexican Population
Official title: Estudio clínico Fase III Para Evaluar la Eficacia terapéutica en Pacientes Mexicanos Con Dislipidemia Mediante el Uso vía Oral de L-Carnitina + Atorvastatina Comparado Con Atorvastatina
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Dyslipidemias
Cardiovascular Risk Factor
Lead sponsor: Laboratorios Grossman, S.A.
Sponsor class: INDUSTRY
Collaborators: name: Instituto Nacional de Salud Publica, Mexico
First posted: 2018-10-05
Enrollment: 120
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Longitudinal
Primary purpose: TREATMENT

Brief summary: Clinical Trial Phase III, experimental, simple blind, randomized with two treatment groups, multicentric, longitudinal, to evaluate the therapuetic efficacy to dislipydemias in mexican adult population. This trial includes homogeneus populations that could be comparable by their disease condition, biologic characteristics and sociodemographics characteristics.

2 Treatment groups: Experimental Group: Oral Administration of L-carnitine (1g) + Oral Atorvastatin (20mg), every 24 hours for 6 months.

Active control group: Oral Administration of Atorvastatin 20mg every 24 hours for 6 months.

Sample Size: 120 subjects, females or males between 35 to 75 years old. Laboratory tests: Hematic biometry, quimical blood components, electrocardiogram and pregnancy urinary test.

Detailed description: General objectives:

Evaluate the therapeutic efficacy in Mexican adults with dyslipidemia through the oral route use of L-carnitine + atorvastatin in comparison with the use of Atorvastatin, after six months of treatment.

Evaluate the safety of the medicines under study.

Hypothesis:

The combined use of L-carnitine + atorvastatin offers therapeutic superiority with respect to the use of atorvastatin as treatment to reduce the percentage of C-LDL in patients with dyslipidemia.

The combination of L-carnitine + atorvastatin shows fewer incidences in the presence of adverse events attributable to the medicine in comparison to the use of atorvastatin as mono-therapy, in the treatment of dyslipidemia patients.

Design:

Phase III clinical assay, experimental randomized with two treatment, multi-centered, longitudinal, to evaluate the therapeutic efficacy in dyslipidemias of Mexican adults.

Material and Methods:

Sample Size 120 subjects will be included. Inclusion Criteria Mexicans between 35 and 75 years of age. Gender indistinct. Patient with abnormal lipid profile considered as serum levels of C-LDL of 100mg/dl or greater obtained by laboratory parameters.

Not under pharmacologic treatment to handle their dyslipidemia or accepting to suspend their current treatment and be evaluated for their inclusion in the next 3 weeks starting on the day of the initial evaluation.

Women in fertile stage with a safe, hormonal-free family planning method. A safe planning method includes surgical methods in women, intrauterine device that doesn't release progestines and use of preservative in all their sexual relations.

Women in fertile stage who don't wish to become pregnant during their participation in the study.

Post-menopause women or with hysterectomy history. Have a fixed and/or mobile telephone and accept to receive calls from the site for study processes.

Grant their duly informed consent. Exclusion Criteria Subject lacking the mental capacity to understand the processes which imply their participation in the study and thus,not capable of granting their participation in a voluntary manner.

History of hypersensitivity to the medicines being studied. Daily intake of at least 240ml of grape juice or sporadic ingestion of 1 liter. Potentially fertile women without a safe family planning method, who wish to become pregnant during the study, are already pregnant or in lactation period.

Having on Globorisk scale for Mexicans, or as an associated risk factor, a high stratification for cardiovascular risk.

Basal laboratory values with elevation of ALT 1.5 times larger than the upper limit considered normal according to international units.

Basal laboratory values with elevation of CPK not attributable to physical activity.

Subjects who are under anti-coagulant treatment, suffer from coagulation disorders, or any circumstance which contraindicates the taking of a blood.

History of acute myocardial infarction, unstable angina, some confirmed coronopathy, arrhythmias, congestive cardiac failure or cerebrovascular disease.

History of muscular conditions of the genetic type or of rhabdomyolysis in patient or first degree relative.

History or diagnose of congenital hepatic disorders, chronic infection by hepatitis virus, hepatitis with fatty liver, alcoholic hepatitis, primary biliary cirrhosis, primary sclerosis, cholangitis or hepatic failure.

History or diagnose of congenital renal disorders, chronic renal failure, acute renal damage or nephritic syndrome.

History of infection by Human Immunodeficiency Virus. History of Acute or Chronic Pancreatitis. History of the following endocrine diseases: non-controlled Diabetes Mellitus, lipodystrophy, thyroid disorders, Cushing Syndrome and/or Polycystic Ovary Syndrome.

Diseases which compromise immunity such as Systemic Lupus Erythematous, Rheumatoid Arthritis, Antiphospholipid Antibodies Syndrome or Psoriasis.

Diseases by deposit such as Gaucher Disease, disease by glycogen deposit, Tay-Sachs juvenile disease or Niemann Pick Disease.

Diagnose of Kawasaki Disease, Werner Syndrome, intermittent acute Porphyria, Idiopathic Hyperkalemia or Klinefelter Syndrome.

Suffer from Idiopathic Hyperkalemia, Klinefelter Syndrome, Werner Syndrome, Kawasaki Disease or Porphyria.

History of epilepsy. History or diagnose of alcoholism. Intake of more than 20g of alcohol per day. User of marihuana. User of illegal drugs.

Intake of medicines with pharmacologic interaction which increase or decrease the efficacy of L-Carnitine and/or atorvastatin or alter the lipids in blood such as:

Macrolide antibiotics: Erythromycin, Telithromycin and Clarithromycin. Azole anti-fungi: Ketoconazole, Itraconazole, Fluconazole and Nefazodone. Quercetin, Amiodarone, Aprepitant, Cimetidine, Ciprofloxacin, Cyclosporine, Diltiazem, Imatinib, Echinacea, Enoxacin, Ergotamine, Metronidazole, Mifepristone, Tofisopam, Gestodene, Verapamil, Mibefradil, Fluoxetine, Phenobarbital, Carbamazepine, Phenytoin, Rifampin, Modafinil, Glucocorticoids, Felbamate, Rosiglitazone, Griseofulvin, Pioglitazone, Gemfibrozil, Clofibrate, Fenofibrate, Niacin, Nefazodone, Cholestyramine, Colchicine, Colestipol, Primidone, Topiramate, Troglitazone, Rifabutin, Digoxin, Thiazides, anabolic Steroids, Progestogens, Estrogens, Danazol, Amiodarone, fibric Acid, docosahexaenoic acid, Isotretinoine, Immunosuppressives, protease inhibitors of HIV or of the Hepatitis C Virus, Inhibitors of the co-transport of sodium-glucose, Tamoxifen, Raloxifene, non-selective Beta blockers, biliary acid sequestrants, asparginase, Sirolimus and Interferon.

Patients who have been diagnosed with terminal conditions. Patients with recent Cancer diagnose or undergoing any type of therapy for same. Patients who have suffered skin cancer not of the melanoma type and have been cured and haven't been on treatment for at least 1 year before the start of their participation in the study may enter.

Patients under lipid lowering treatment and who, because of their clinical condition aren't candidates to the period of lavage or detoxification; or well reject same.

Been participating in another clinical trial or having concluded their participation in the 30 days previous to beginning their participation in this study.

Any other which, at the Investigator's criteria, puts at risk the safety of the participant and/or interferes with the results of the study.

Medicine L-Carnitine, Atorvastatin Dose L-Carnitine 1 g + Atorvastatin 20 mg daily for 6 months and Atorvastatin 20 mg daily for 6 months

Efficacy criteria:

The efficacy of the combined treatment vs. atorvastatin in mono-therapy for dyslipidemia will be compared, through evaluation of the variability of the biochemical parameters at the start and end of the study.

Eligibility criteria: Inclusion Criteria:

* Mexicans between 35 and 75 years of age.
* Gender indistinct.
* Patient with abnormal lipid profile considered as serum levels of Cholesterol LDL of 100mg/dl or greater, obtained by laboratory parameters.
* Not being under pharmacologic treatment to manage its dyslipidemia or accept to suspend current treatment and be evaluated for inclusion in the next 3 weeks starting on the day of initial evaluation.
* Women in fertile stage with a safe, hormonal-free family planning method. A safe planning method includes surgical methods in women, intrauterine device that doesn't release progestines and use of preservative in all their sexual relations.
* Women in fertile stage who don't wish to become pregnant during their participation in the study.
* Post-menopause women or with hysterectomy history.
* Have a fixed and/or mobile telephone and accept to receive calls from the site for study processes.
* Grant their duly informed consent.

Exclusion Criteria:

* Subject lacking the mental capacity to understand the processes which imply their participation in the study and thus, not capable of granting their participation in a voluntary manner
* History of hypersensitivity to the medicines being studied.
* Daily intake of at least 240 mL of grape juice or sporadic ingestion of 1 liter.
* Potentially fertile women without a safe family planning method, who wish to become pregnant during the study, are already pregnant or in lactation period.
* Having on Globorisk scale for Mexicans, or as an associated risk factor, a high stratification for cardiovascular risk.
* Basal laboratory values with elevation of ALT 1.5 times larger than the upper limit considered normal according to international units.

Basal laboratory values with elevation of CPK not attributable to physical activity.

* Subjects who are under anticoagulant treatment, suffer from coagulation disorders, or any circumstance which contraindicates the taking of a blood.
* History of acute myocardial infarction, unstable angina, some confirmed coronopathy, arrhythmias, congestive cardiac failure or cerebrovascular disease.
* History of muscular conditions of the genetic type or of rhabdomyolysis in the patient or first degree relative.
* History or diagnose of congenital hepatic disorders, chronic infection by hepatitis virus, hepatitis with fatty liver, alcoholic hepatitis, primary biliary cirrhosis, primary sclerosis, cholangitis or hepatic failure.
* History or diagnose of congenital renal disorders, chronic renal failure, acute renal damage or nephritic syndrome.
* History of infection by Human Immunodeficiency Virus.
* History of Acute or Chronic Pancreatitis.
* History of the following endocrine diseases: non controlled Diabetes Mellitus, lipodystrophy, thyroid disorders, Cushing Syndrome and or Polycystic Ovary Syndrome.
* Diseases which compromise immunity such as Systemic Lupus Erythematous, Rheumatoid Arthritis, Antiphospholipid Antibodies Syndrome or Psoriasis.

Diseases by deposit such as Gaucher Disease, disease by glycogen deposit, Tay Sachs juvenile disease or Niemann Pick Disease.

* Diagnose of Kawasaki Disease, Werner Syndrome, intermittent acute Porphyria, Idiopathic Hyperkalemia or Klinefelter Syndrome
* Suffer from Idiopathic Hyperkalemia, Klinefelter Syndrome, Werner Syndrome, Kawasaki Disease or Porphyria.
* History of epilepsy.
* History or diagnose of alcoholism.
* Intake of more than 20 grams of alcohol per day.
* User of marihuana.
* User of illegal drugs.
* Intake of medicines with pharmacologic interaction which increase or decrease the efficacy of L Carnitine and or atorvastatin or alter the lipids in blood such as Erythromycin, Telithromycin and Clarithromycin. Azole antifungi as Ketoconazole, Itraconazole, Fluconazole and Nefazodone. Quercetin, Amiodarone, Aprepitant, Cimetidine, Ciprofloxacin, Cyclosporine, Diltiazem, Imatinib, Echinacea, Enoxacin, Ergotamine, Metronidazole, Mifepristone, Tofisopam, Gestodene, Verapamil, Mibefradil, Fluoxetine, Phenobarbital, Carbamazepine, Phenytoin, Rifampin, Modafinil, Glucocorticoids, Felbamate, Rosiglitazone, Griseofulvin, Pioglitazone, Gemfibrozil, Clofibrate, Fenofibrate, Niacin, Nefazodone, Cholestyramine, Colchicine, Colestipol, Primidone, Topiramate, Troglitazone, Rifabutin, Digoxin, Thiazides, anabolic Steroids, Progestogens, Estrogens, Danazol, Amiodarone, fibric Acid, docosahexaenoic acid, Isotretinoine, Immunosuppressives, protease inhibitors of HIV or of the Hepatitis C Virus, Inhibitors of the cotransport of sodium glucose, Tamoxifen, Raloxifene, non selective Beta blockers, biliary acid sequestrants, asparginase, Sirolimus and Interferon.
* Patients who have been diagnosed with terminal conditions.
* Patients with recent Cancer diagnose or undergoing any type of therapy for same.
* Patients who have suffered skin cancer not of the melanoma type and have been cured and haven't been on treatment for at least 1 year before the start of their participation in the study may enter.
* Patients under lipid lowering treatment and who, because of their clinical condition aren't candidates to the period of lavage or detoxification; or well reject it.
* Being participating in another clinical trial or having concluded their participation in the 30 days previous to beginning their participation in this study.
* Any other which, at the Investigator's criteria, puts at risk the safety of the participant and or interferes with the results of the study.

Primary outcomes:
measure: Efficacy of experimental treatment by the change in Cholesterol LDL
timeFrame: 6 months
Secondary outcomes:
measure: Efficacy of experimental treatment by the change in Cholesterol no-HDL
timeFrame: 6 months
measure: Efficacy of experimental treatment by the change in Total serum Cholesterol
timeFrame: 6 months
measure: Efficacy of experimental treatment by the change in Triglycerides
timeFrame: 6 months
measure: Efficacy of experimental treatment by the change in Cholesterol HDL
timeFrame: 6 months
measure: Incidence of Treatment-Emergent Adverse Events (safety and tolerability)
timeFrame: 6 months
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Laboratorios Grossman Sa
Study officials:
affiliation: Instituto Nacional de Salud Pública
name: Aurelio Cruz Valdez, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: JM Research, SC
name: José Flores Figueroa, PhD
role: PRINCIPAL_INVESTIGATOR
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