Evaluation of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TA-8995 With Single, Escalating 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 and tolerability of single doses of TA-8995 in healthy Caucasian and Japanese volunteers.

Official Title
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A Randomised, Double-blind, Placebo-controlled, First Time-in-humans Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single, Escalating Doses of TA-8995 in Healthy 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: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasian men aged 18-55 years and ≥65 years Women of non-childbearing potential Japanese men aged 18-55 years Subjects were deemed healthy on the basis of medical history, physical examination, Electrocardiogram (ECG), vital signs and safety tests of blood and urine Subjects were able to give fully informed written consent Exclusion Criteria: HDL-C level ≥2.59 mmol/L Abnormal Holter ECG Family history of long QT syndrome, hypokalaemia or Torsade de Pointes Vital signs or 12-lead ECG values outside the acceptable range Positive tests for hepatitis B and C, HIV 1 and 2 Positive urine pregnancy test (women only) Severe adverse reaction or allergy to any drug Drug or alcohol abuse Smoking within the 6 months before dosing with TA-8995 (Caucasian subjects), or smoking more than 10 cigarettes daily (Japanese subjects) Over-the-counter or prescribed medication up to 7 days or 5 half-lives (whichever was longer) before dosing with TA-8995 Consuming food or drinks containing grapefruit or cranberry within the 7 days before dosing Participation in other clinical trials, or loss of more than 450 mL blood within the previous 3 months Clinically relevant abnormal findings at the screening assessment Clinically relevant abnormal medical history or concurrent medical condition Possibility that volunteer would not cooperate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single ascending dose in Caucasian men<br> | Drug: TA-8995<br>* TA-8905 5, 10, 25, 50 (fasted and fed), 100 and 150 mg<br>|
| Experimental: Age-effect in Caucasian men<br> | Drug: TA-8995<br>* Drug: TA-8995 25 mg<br>|
| Experimental: Gender-effect in Caucasian women<br> | Drug: TA-8995<br>* Drug: TA-8995 25 mg<br>|
| Experimental: Single ascending dose in Japanese men<br> | Drug: TA-8995<br>* Drug: TA-8995 25, 50, 100 and 150 mg<br>|
| Placebo Comparator: Placebo: Single ascending dose in Caucasian men<br> | Drug: Placebo<br>* Single ascending dose in Caucasian men<br>|
| Placebo Comparator: Placebo: Age-effect in Caucasian men<br> | Drug: Placebo<br>* Age-effect in Caucasian men<br>|
| Placebo Comparator: Placeo: Gender-effect in Caucasian women<br> | Drug: Placebo<br>* Gender-effect in Caucasian women<br>|
| Placebo Comparator: Placebo: Single ascending dose in Japanese men<br> | Drug: Placebo<br>* Single ascending dose in Japanese men<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 | 
| Peak concentration (ng/mL) of TA-8995 |  | 336 hours post dose | 
| Time of peak concentration (hr) of TA-8995 |  | 336 hours post dose | 
| Area under the concentration-time curve (mg/L・hr) up to 24 h (AUC0-24), 72 h (AUC0-72), 168 h (AUC0-168), 336 h (AUC0-336) and infinity (AUC0-∞) of TA-8995 |  | 336 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Cholesterol Ester Transfer Protein (CETP) activity (%) and concentration (mg/mL) |  | 336 hours post 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