Evaluation of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TA-8995 After Multiple Doses in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of TA-8995 after multiple doses in healthy adult male subjects

Official Title
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A Randomised Double-blind, Placebo-controlled, Ascending-dose, Phase I Study to Determine the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TA-8995 After Multiple Doses in Healthy Adult Male Subjects

Conditions
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Dyslipidemia

Intervention / Treatment
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* Drug: TA-8995
* Drug: TA-8995
* Drug: TA-8995
* Drug: TA-8995
* Drug: TA-8995
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Free from any clinically significant illness or disease as determined by their medical history, physical examination, laboratory and other tests and as judged by the Investigator. Between 18 - 55 years old. Male of Caucasian ethnic origin. Body mass index (BMI) in the range of 19 - 33 kg/m² and had a minimum weight of 50 kg. Subjects with a BMI in the range 30.0 - 33.0 kg/m² had to have a waist measurement of ≤ 91 cm. Exclusion Criteria: High density lipoprotein (HDL)-C level of greater or equal to 2.59 mmol/L (≥ 100 mg/dL) at Screening. Abnormal Electrocardiogram (ECG) at Screening or Day -1 including a QTc ≥ 430 ms (The QTc-interval was calculated automatically according to Bazett's formula. In the case of results of ≥ 430 ms, QTc was additionally calculated manually using Fridericia's formula which was used as an exclusion criterion). Family history of long QT syndrome, hypokalaemia or Torsades de Pointes Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease or history of any psychotic illness Presence or history of gastro-intestinal, hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TA-8995 1 mg<br> | Drug: TA-8995<br>* Drug: TA-8995 1mg<br>|
| Experimental: TA-8995 2.5 mg<br> | Drug: TA-8995<br>* Drug: TA-8995 2.5mg<br>|
| Experimental: TA-8995 5 mg<br> | Drug: TA-8995<br>* Drug: TA-8995 5mg<br>|
| Experimental: TA-8995 10 mg<br> | Drug: TA-8995<br>* Drug: TA-8995 10mg<br>|
| Experimental: TA-8995 25 mg<br> | Drug: TA-8995<br>* Drug: TA-8995 25mg<br>|
| Placebo Comparator: Placebo (TA-8995 1mg)<br> | Drug: Placebo<br>* Placebo (TA-8995 1mg)<br>|
| Placebo Comparator: Placebo (TA-8995 2.5mg)<br> | Drug: Placebo<br>* Placebo (TA-8995 2.5mg)<br>|
| Placebo Comparator: Placebo (TA-8995 5mg)<br> | Drug: Placebo<br>* Placebo (TA-8995 5mg)<br>|
| Placebo Comparator: Placebo (TA-8995 10mg)<br> | Drug: Placebo<br>* Placebo (TA-8995 10mg)<br>|
| Placebo Comparator: Placebo (TA-8995 25mg)<br> | Drug: Placebo<br>* Placebo (TA-8995 25mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | 336 hours post dose | 
| Laboratory tests (haematology, biochemistry and urinalysis) |  | 336 hours post dose | 
| Vital signs (supine systolic and diastolic blood pressure, heart rate and body temperature) |  | 336 hours post dose | 
| Area under the plasma concentration (AUC) versus time curve over the final dosing interval (AUC0-τ, Steady-state) |  | 7 days post the final dose | 
| The last time point 't' with a concentration Ct ≥ Lower limit quantification (LLQ) (AUC0-t, Steady-state) |  | 7 days post the final dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cholesterol ester transfer protein (CETP) activity (%) |  | 7 days post the final dose | 
| CETP concentration (mg/mL) |  | 4 hours after the first and the fibal dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MT-8995, Dyslipidemia, Cholesteryl ester transfer proteins