Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAP311 in Healthy Subjects and Dyslipidemic Patients

Study Overview
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Brief Summary
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This study will assess the safety, tolerability, and effect of TAP311 on blood lipids in healthy subjects and in patients who have dyslipidemia. The effect of food on TAP311 concentration in blood and effect of TAP311 administration on simvastatin concentration will also be assessed in healthy volunteers.

Official Title
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A First-in-human Randomized, Double-blind, Placebo-controlled, 4-part Study to Assess Safety, Tolerability, Pharmacokinetics (Including Open Label Study of Food Effect and Interaction With Simvastatin) and Pharmacodynamics of Interwoven Single- and Multiple-ascending Doses of TAP311 in Healthy Subjects and Dyslipidemic Patients.

Conditions
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Dyslipidemia, Healthy Volunteers

Intervention / Treatment
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* Drug: TAP311


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects age 18 to 65 years of age included, and in good health as determined by past medical history, physical examination, electrocardiogram, and laboratory tests at screening. OR untreated dyslipidemic patients. Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 36 kg/m2. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Exclusion Criteria: Use of other investigational drugs at the time of enrollment. Active treatment for type 1 diabetes or type 2 diabetes mellitus. A past medical history of ECG abnormalities, documented cardiac arrhythmias or cardiovascular diseases. History of malignancy of any organ system, treated or untreated, within the past 5 years. Pregnant or nursing (lactating) women. Smokers. Use of any prescription drugs, herbal supplements and/or over-the-counter (OTC) medication, dietary supplements. History of drug or alcohol abuse within the 12 months prior to dosing. Any surgical or medical condition, acute or unstable chronic disease which may, based on the investigator's opinion, jeopardize the patient in case of participation in the study Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAP311 in Healthy Volunteers<br> | Drug: TAP311<br> <br> |
| Placebo Comparator: Matching Placebo<br>Healthy Volunteers and Patients will be treated in Placebo group. | Drug: TAP311<br> <br> |
| Experimental: TAP311 and Simvastatin<br> | Drug: TAP311<br> <br> |
| Experimental: TAP311 in Patients<br> | Drug: TAP311<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of single and multiple doses of TAP311 in healthy subjects and patients with dyslipidemia | Number of patients with adverse events and changes from baseline in vital signs, ECG and clinical labs (blood chemistry, hematology and urinalysis). | Up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TAP311 concentrations in blood and urine following administration of single and multiple doses in healthy subjects and in patients with dyslipidemia. |  | 25 timepoints over 17 days | 
| Effect of TAP311 administration on simvastatin (and metabolite) blood concentration in healthy subjects. | Simvastatin (and metabolite) blood concentration before and after TAP311 treatment. | 10 days | 
| Effect of food on TAP311 blood concentration in healthy subjects. | TAP311 blood concentration when the drug is administered with and without food. | 3 days | 
| Effects of TAP311 on total cholesterol in patients with dyslipidemia | Total cholesterol blood concentration before and after TAP311 treatment. | 8 timepoints over 15 days | 
| Effects of TAP311 on Low Density Lipoprotein (LDL-C) in patients with dyslipidemia | LDL-C blood concentration before and after TAP311 treatment. | 8 timepoints over 15 days | 
| Effects of TAP311 on high density lipoprotein (HDL-C)in patients with dyslipidemia. | HDL-C blood concentration before and after TAP311 treatment. | 8 timepoints over 15 days | 
| Effects of TAP311 on triglycerides in patients with Dyslipidemia | Triglycerides concentration in blood before and after TAP311 treatment. | 8 timepoints over 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High cholesterol levels, Hyperlipidemia, High-density Lipoprotein, Low-density Lipoprotein, Simvastatin