araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Efficacy and Safety Evaluation of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia on Lipid Modifying Therapy (ODYSSEY JAPAN)

Summary: Primary Objective:
  To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable daily statin therapy with or without other lipid modifying therapy in comparison with placebo after 24 weeks of treatment in heterozygous familial hypercholesterolemia (HeFH) or high cardiovascular risk participants with hypercholesterolemia.
  Secondary Objectives:
  -  To evaluate the effect of alirocumab in comparison with placebo on LDL-C after 12 weeks of treatment.
  -  To evaluate the effect of alirocumab on other lipid parameters.
  -  To evaluate the long-term effect of alirocumab in comparison with placebo on LDL-C after 52 weeks of treatment.
  -  To evaluate the safety and tolerability of alirocumab.
  -  To evaluate the development of anti-alirocumab antibodies.
  -  To evaluate the pharmacokinetics of alirocumab.

Detailed description: Total duration per participant of approximately 63 weeks (14 months) (screening: 3 weeks, double-blind treatment period: 52 weeks, and follow-up period: 8 weeks).

Eligibility: Inclusion criteria:
  Participants with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia who were not adequately controlled with a stable daily dose of statin with or without other lipid modifying therapy, at stable dose prior to the screening visit (Week -3).
  Exclusion criteria:
  1. LDL-C <100 mg/dL (<2.59 mmol/L) at the screening visit in participants with heterozygous familial hypercholesterolemia or in participants with non-familial hypercholesterolemia who had a history of documented coronary heart disease as described in Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
  2. LDL-C <120 mg/dL (<3.10 mmol/L) at the screening visit in participants with non-familial hypercholesterolemia who had a history of documented diseases or other risk factors as categorized in primary prevention category III as described in JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012.
  3. Not on a stable daily dose of lipid modifying therapy (including statin) within 4 weeks prior to the screening visit or between screening and randomization visits.
  4. Age <20 years at the screening visit.
  The above information is not intended to contain all considerations relevant to a participants' potential participation in a clinical trial.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Study of Polymorphisms of RAAS and MMPs in Acute Heart Failure

Summary: this study aim to investigate the:
  -  association of RAAS polymorphisms and AHF
  -  association of MMP 3 and 12 polymorphisms and AHF

Detailed description: Heart failure can be defined as a complex clinical syndrome that results from any structural or functional disorder of the heart, with impairment of ability to fill the ventricles or eject blood. The main event of the IC is dyspnea and fatigue, which limit exercise tolerance and induces water retention.
  The renin angiotensin aldosterone system governs the salt and water homeostasis in the body. Renin is a proteolytic enzyme secreted by the juxtaglomerular apparatus of the kidney (area near the glomeruli). Renin has no direct action on the organism, but that is part of the renin-angiotensin system or the renin-angiotensin-aldosterone system is known.
  To date, few published studies have examined the association between the polymorphism AGT M235T * and cardiac dysfunction; and available results are contradictory. What is not known yet is the ratio of this polymorphism with the prognosis of heart failure.

Eligibility: Inclusion Criteria:
  -  aged more than 18 year old.
  -  acute non traumatic dyspnea .
  Exclusion Criteria:
  -  ECG diagnostic for acute myocardial infarction or ischemic chest pain within the prior 24 hours
  -  a history of a heart transplant, pericardial effusion, chest wall deformity suspected of causing dyspnea
  -  coma, shock,MV,vasopressor drugs
  -  arrhythmia serious and sustained,
  -  pace maker
  -  severe mitral valve disease,

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome

Summary: The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 52 weeks in patients with Familial Chylomicronemia Syndrome


Eligibility: Inclusion Criteria:
  -  History of chylomicronemia
  -  A diagnosis of Familial Chylomicronemia Syndrome (Type 1 Hyperlipoproteinemia)
  -  Fasting triglycerides ≥ 750 mg/dL (8.4 mmol/L) at Screening
  Exclusion Criteria:
  -  Diabetes mellitus if newly diagnosed or if HbA1c ≥ 9.0%
  -  Other types of severe hypertriglyceridemia
  -  Active pancreatitis within 4 weeks of screening
  -  Acute Coronary Syndrome within 6 months of screening
  -  Major surgery within 3 months of screening
  -  Treatment with Glybera therapy within 2 years of screening
  -  Previous treatment with IONIS-APOCIIIRx
  -  Have any other conditions in the opinion of the investigator which could interfere with the patient participating in or completing the study

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Relationships Between Plasma PCSK9 Levels, LDL-cholesterol Concentrations and Lipoprotein (a) Levels in Familial Hypercholesterolemia

Summary: Familial hypercholesterolemia (FH) is an autosomal codominant single gene disorder caused by mutations in the LDL receptor gene (LDLR) that disrupt the normal clearance of LDL particles from the plasma. Heterozygous patients (HeFH) present a two- to three-fold raise in plasma LDL-cholesterol (LDL-C) concentrations and coronary artery disease occurs earlier among HeFH carrying negative-receptor (NR) mutations as compared with HeFH subjects carrying defective-receptor (DR) variants. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL-C levels by binding to LDLR and by enhancing its intracellular degradation.
  The objective of this study is to examine to what extent variations in LDL-C and Lipoprotein (Lp) (a) concentrations are related to PCSK9 levels in a large French-Canadian cohort of HeFH subjects.
  The primary hypothesis is that that PCSK9 levels have a significant impact on LDL-C concentration variability and are associated with Lp(a) levels.


Eligibility: Inclusion Criteria:
  Subjects with familial hypercholesterolemia:
  -  Aged between 18-65 years
  -  Carrier of a mutation in the LDL receptor gene
  Controls:
  -  Aged between 18-60 years
  -  HDL-cholesterol > 1.1 mmol/L
  -  Triglycerides < 1.7 mmol/L
  -  Fasting blood glucose <6.1 mmol/L
  -  Normal blood pressure (<130/85)
  Exclusion Criteria:
  -  Subjects with a previous history of cardiovascular disease
  -  Subjects with Type 2 diabetes
  -  Were pregnant or nursing;
  -  Subjects with a history of cancer
  -  Subjects with acute liver disease, hepatic dysfunction, or persistent elevations of serum transaminases
  -  Subjects with a secondary hyperlipidemia due to any cause
  -  History of alcohol or drug abuse within the past 2 years
  -  hormonal treatment
  -  Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study

Relevance to patient case: definitely relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: A Study of Evacetrapib (LY2484595) in Combination With Atorvastatin in Japanese Participants With Primary Hypercholesterolemia

Summary: The main purpose of this study is to evaluate the efficacy and safety of the study drug known as evacetrapib when administered in combination with atorvastatin for 12 weeks in Japanese participants with primary hypercholesterolemia.


Eligibility: Inclusion Criteria:
  -  Must be treated with atorvastatin 10 mg/day for at least 30 days prior to study initiation.
  -  Japanese outpatients who are diagnosed with primary hypercholesterolemia with LDL-C levels (measured by a direct method) that meet the following criteria. (Participant categories are based on the definition in Japan Atherosclerosis Society 2012 guidelines.)
  -  Category I: 160 mg/deciliter (dL)≤LDL-C
  -  Category II: 140 mg/dL≤LDL-C
  -  Category III: 120 mg/dL≤LDL-C
  -  Secondary prevention: 100 mg/dL≤LDL-C
  -  Have triglycerides (TG) ≤400 mg/dL.
  -  Have HDL-C <100 mg/dL.
  Exclusion Criteria:
  -  Participants on LDL apheresis or plasma apheresis.
  -  Participants with secondary hypercholesterolemia or homozygous familial hypercholesterolemia.
  -  Any planned angiography. If angiography is planned, participants may be screened and enrolled after all such planned procedures are completed.
  -  History of any of the following conditions < 90 days prior to study initiation
  -  acute coronary syndrome (unstable angina, acute myocardial infarction)
  -  symptomatic peripheral arterial disease
  -  invasive treatment of carotid artery disease
  -  ischemic stroke or transient ischemic attack (TIA)
  -  intracranial hemorrhage
  -  History of abdominal aortic aneurysm.
  -  Participants with a history of intolerance/hypersensitivity to ezetimibe or statins.
  -  Have systolic blood pressure (SBP) > 160 millimeters of mercury (mm Hg) or diastolic blood pressure (DBP) > 100 mm Hg.
  -  Have a hemoglobin A1c ≥8.4% (National Glycohemoglobin Standardization Program).
  -  During the study period, participants who plan to use, are likely to require, or unwilling or unable to stop with adequate washout any prescription, over the counter (OTC) medication, supplements or health foods with the intent to treat serum lipids (LDL-C, HDL-C, TG) including but not limited to these classes of drugs: statin (except for atorvastatin 10 mg), ezetimibe, bile acid sequestrant, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Participants taking probucol, fibrate or nicotinic agents within 8 weeks before study initiation are excluded from the study.
  -  Have been exposed to cholesteryl ester transfer protein (CETP) inhibitors (for example, anacetrapib or dalcetrapib).

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Estimation Study to Assess the Effect of Severe Renal Impairment and End-stage Renal Disease Hemodialysis on the Pharmacokinetics of Evolocumab

Summary: The primary objective of this study was to evaluate the pharmacokinetics of evolocumab after a single 140 mg subcutaneous (SC) dose in aduts with normal renal function or severe renal impairment or end-stage renal disease (ESRD) receiving hemodialysis.


Eligibility: Inclusion Criteria:
  -  Body mass index (BMI) of ≥ 18 and ≤ 35 kg/m² at screening.
  -  Subjects will have low-density lipoprotein cholesterol (LDL-C) of 70-190 mg/dL (inclusive) and on statin therapy.
  -  Other inclusion criteria may apply.
  Exclusion Criteria:
  -  Subject with current or prior history of statin intolerance
  -  Subject has previously received Evolocumab (AMG 145) or any other investigational therapy directed against PCSK9
  -  Known substance abuse (eg, alcohol, licit or illicit drugs) within 12 months of day -1
  -  Testing positive for alcohol and/or drugs-of-abuse at screening, day -1, or day 1 (alcohol only)
  -  History of hypersensitivity or allergic reaction to mammalian-derived drug preparations
  -  Known sensitivity to any of the active substances or their excipients to be administered during dosing, eg, carboxymethylcellulose
  -  Other exclusion criteria may apply.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: A Phase 1 Study of an Investigational Drug, ALN-PCSSC, in Subjects With Elevated Low Density Lipoprotein Cholesterol (LDL-C)

Summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-PCSSC in subjects with elevated LDL-C.


Eligibility: Inclusion Criteria:
  -  Adequate complete blood counts, liver and renal function
  -  Female subjects must be of non-childbearing potential; e.g. post-menopausal or pre-menopausal with surgical sterilization
  -  Male subjects agree to use appropriate contraception
  -  Willing to provide written informed consent and willing to comply with study requirements.
  -  Non-smokers and non-nicotine users for at least 90 days before screening
  -  On stable statin co-medication [for designated multiple dose cohorts only]
  Exclusion Criteria:
  -  Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk
  -  Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study
  -  History of multiple drug allergies or intolerance to subcutaneous injection
  -  Received any medication or nutraceutical to alter serum lipids within 30 days before screening (non-statin cohorts only)

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Study of Alirocumab (REGN727/SAR236553) in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) Undergoing Low-density Lipoprotein (LDL) Apheresis Therapy

Summary: This is a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the effect of alirocumab in comparison with placebo on the frequency of LDL apheresis treatments in patients with HeFH undergoing LDL apheresis therapy.


Eligibility: Inclusion Criteria:
  1. Men and women ≥18 years of age at the time of the screening visit
  2. Diagnosis of HeFH (Heterozygous familial hypercholesterolemia)
  3. Currently undergoing LDL (low-density lipoprotein) apheresis therapy QW (weekly) or Q2W (every 2 weeks) or at least 8 weeks prior to the screening visit
  Exclusion Criteria:
  1. Homozygous FH (familial hypercholesterolemia)
  2. Background medical LMT (lipid-modifying therapy) (if applicable) that has not been stable for at least 8 weeks prior to the screening visit
  3. LDL apheresis schedule/ apheresis settings that have not been stable for at least 8 weeks prior to the screening visit
  4. An LDL apheresis schedule other than QW to Q2W
  5. Initiation of a new exercise program or exercise that has not remained stable within 8 weeks prior to the screening visit (week -2)
  6. Initiation of a new diet or a diet that has not been stable within 8 weeks prior to the screening visit (week -2)
  7. Use of nutraceuticals or over-the-counter therapies known to affect lipids, at a dose/amount that has not been stable for at least 8 weeks prior to the screening visit (week -2), or between the screening and randomization visit
  8. Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
  9. Known history of a positive test for human immunodeficiency virus
  10. Use of any active investigational drugs within 1 month or 5 half-lives of screening, whichever is longer
  11. Patients who have been treated with at least 1 dose of alirocumab or any other anti-PCSK9 monoclonal antibody in any other clinical studies
  12. Pregnant or breastfeeding women

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: A Study to Identify and Characterize LAL-D Patients in High-risk Populations

Summary: The objective of this study is to determine the frequency of Lysosomal Acid Lipase Deficiency (LAL D) by lysosomal acid lipase (LAL) enzyme activity assay in patients who are considered to be at risk.


Eligibility: Inclusion Criteria:
  1. Non-obese** patients with elevated low-density lipoprotein (LDL)
  2. Non-obese** patients with low high-density lipoprotein (HDL)
  3. Non-obese** patients with unexplained and persistently elevated liver transaminases,
  4. Non-obese** patients with hepatomegaly
  5. Patients with cryptogenic cirrhosis
  6. Patients with biopsy-proven microvesicular or mixed micro/macrovesicular steatosis without a known etiology
  7. Patients with presumed Familial Hypercholesterolemia (FH) in which genetic analysis was performed for the genes encoding the low-density lipoprotein receptor (LDLR), Apo-B and PCSK9 genes and no disease-causing mutations were identified
  8. Patients with presumed FH with unclear family history
  9. Patients with autosomal recessive hypercholesterolemia (other than homozygous FH)
  10. Patients with autosomal recessive low HDL of unknown etiology
  Also, patient must meet the following:
  -  Patient or patient's parent or legal guardian (if applicable) consents to participate in the study and provides informed consent prior to any study procedures being performed. If the patient is of minor age; he/she is willing to provide assent where required per local regulations, and if deemed able to do so.
  -  Patient is willing and able to comply with protocol requirements.
  -  Patients who do not fall into one of the aforementioned categories (cohorts) but are considered highly suspicious for LAL D should be tested to rule out the disorder outside of the study at the discretion of the Investigator.
  Exclusion Criteria:
  -  Active viral hepatitis;
  -  Other confirmed genetic liver diseases (e.g., Wilson's disease, hemochromatosis, alpha 1-antitrypsin).

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: A 2-Part, Phase 1, Single and Multiple Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of CAT-2054 in Healthy Subjects

Summary: This is a 2-part, Phase 1, placebo-controlled, double-blind, randomized, single and multiple ascending dose study. CAT-2054 will be administered either as an uncoated capsule (CAT-2054) or a coated capsule (CAT-2054-C). In Part A, CAT-2054 or placebo is administered as a single dose in a fasting state at 4 dose levels; at 3 dose levels, subjects will return for a second dose of the study drug after a high-fat meal. Additionally, at 1 dose level, CAT-2054-C or placebo will be administered as a single dose in a fasting state, and subjects will return for a second dose of the study drug after a high-fat meal. In Part B, CAT-2054 will be administered as multiple ascending doses at 4 dose levels for 14 consecutive days. In selected cohorts, CAT-2054, CAT-2054-C or CAT-2054 with atorvastatin will be dosed to assess safety in anticipation of future clinical trials.


Eligibility: Inclusion Criteria:
  -  Provision of written informed consent before any study-specific procedure
  -  Good health as determined by medical history, physical examination, vital sign measurements, ECG, and clinical laboratory measurements
  -  Satisfies one of the following:
  1. Females not of childbearing potential: non-pregnant and non-lactating surgically sterile or postmenopausal 2 years or less with a follicle-stimulating hormone assessment greater than or equal to 40 IU/L
  2. Males: surgically sterile, abstinent, or subject or partner is utilizing an acceptable contraceptive method during and 3 months after the last study dose
  -  For Part B only, measured at Screening: Fasting LDL-C ≥100 mg/dL; or (Cohort B6 only) fasting LDL-C ≥130 mg/dL
  -  Body mass index (BMI) between 18 and 30 kg/m², inclusive, for Part A and between 18 and 40 kg/m², inclusive, for Part B, and body weight >50 kg at Screening
  Exclusion Criteria:
  -  Use of prescription drugs or non-prescription drugs including herbals, and dietary supplements (including multivitamins and any product containing niacin or omega-3 fatty acids above the Recommended Daily Allowance) within 2 weeks before dosing. Additionally for Part B only, use of any lipid-regulating prescription drug, non-prescription drug, herbal, or dietary supplement within 6 weeks before dosing
  -  Clinically significant disease that requires a physician's care and/or would interfere with study evaluations
  -  Clinically significant electrocardiogram (ECG) abnormalities or laboratory results as assessed by the investigator, such as QTcF >450
  -  Use of any investigational drug or participation in any investigational study within 30 days prior to screening or 5 half-lives of the study agent, whichever is longer

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Trial Assessing Efficacy, Safety and Tolerability of PCSK9 Inhibition in Paediatric Subjects With Genetic LDL Disorders

Summary: A study to assess safety and efficacy of evolocumab (AMG-145) in paediatric subjects aged 10-17 years diagnosed with heterozygous familial hypercholesterolemia.

Detailed description: A study to evaluate the effect of 24 weeks of subcutaneous (SC) evolocumab compared with placebo,when added to standard of care, on percent change from baseline in low‑density lipoprotein cholesterol (LDL-C) in pediatric subjects 10 to 17 years of age with HeFH

Eligibility: Inclusion Criteria:
  -  Male or female ≥ 10 to ≤ 17 years of age (before 18th birthday)
  -  Diagnosis of heterozygous familial hypercholesterolemia
  -  On an approved statin with stable optimized dose for ≥ 4 weeks
  -  Other lipid-lowering therapy stable for ≥ 4 weeks (fibrates must be stable for ≥ 6 weeks)
  -  Fasting LDL-C ≥ 130 mg/dL (3.4 mmol/L)
  -  Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)
  Exclusion Criteria:
  -  Type 1 diabetes, or type 2 diabetes that is or poorly controlled
  -  Uncontrolled hyperthyroidism or hypothyroidism
  -  Cholesterylester transfer protein (CETP) inhibitor in the last 12 months, or mipomersen or lomitapide in the last 5 months
  -  Previously received evolocumab or any other investigational therapy to inhibit PCSK9.
  -  Lipid apheresis within the last 12 weeks prior to screening.
  -  Homozygous Familial Hypercholesterolemia

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Drug Interaction Study Between AVP-923 and Itraconazole and Between AVP-786 and Itraconazole in Healthy Adult Subejcts

Summary: The purpose of this study is to determine the effects of a potent CYP3A4 inhibitor, itraconazole, on the steady-state PK of AVP-923 and AVP-786.

Detailed description: A Phase 1, single-center, randomized, double-blind, double-dummy drug interaction study.

Eligibility: Inclusion Criteria:
  -  Healthy adult males and females, 18 to 55 years of age
  -  Body Mass Index (BMI) ≥19 and ≤30 kg/m2 (for both males and females)
  Exclusion Criteria:
  -  History or presence of significant disease
  -  History of substance abuse or dependence (except caffeine), or treatment for substance use disorder(s) within the year prior to screening or within 6 months for nicotine including e-cigarettes
  -  Use of any tobacco-containing or nicotine-containing products within 6 months prior to the first dose
  -  Use of any prescription or the over-the-counter medications within 14 days

Relevance to patient case: not relevant