Evaluation of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TA-8995 With Single, Escalating Doses in Healthy Subjects

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

The purpose of this study is to assess the safety and tolerability of single doses of TA-8995 in healthy Caucasian and Japanese volunteers.

Study Overview

• Status: Completed
• Conditions: Dyslipidemia
• Intervention / Treatment: Drug: TA-8995; Drug: TA-8995; Drug: TA-8995; Drug: Placebo; Drug: Placebo; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7EW
    • Hammersmith Medicines Research (HMR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single ascending dose in Caucasian men	Drug: TA-8995; TA-8905 5, 10, 25, 50 (fasted and fed), 100 and 150 mg; Drug: TA-8995; Drug: TA-8995 25 mg; Drug: TA-8995; Drug: TA-8995 25, 50, 100 and 150 mg
Experimental: Age-effect in Caucasian men	Drug: TA-8995; TA-8905 5, 10, 25, 50 (fasted and fed), 100 and 150 mg; Drug: TA-8995; Drug: TA-8995 25 mg; Drug: TA-8995; Drug: TA-8995 25, 50, 100 and 150 mg
Experimental: Gender-effect in Caucasian women	Drug: TA-8995; TA-8905 5, 10, 25, 50 (fasted and fed), 100 and 150 mg; Drug: TA-8995; Drug: TA-8995 25 mg; Drug: TA-8995; Drug: TA-8995 25, 50, 100 and 150 mg
Experimental: Single ascending dose in Japanese men	Drug: TA-8995; TA-8905 5, 10, 25, 50 (fasted and fed), 100 and 150 mg; Drug: TA-8995; Drug: TA-8995 25 mg; Drug: TA-8995; Drug: TA-8995 25, 50, 100 and 150 mg
Placebo Comparator: Placebo: Single ascending dose in Caucasian men	Drug: Placebo; Single ascending dose in Caucasian men; Drug: Placebo; Age-effect in Caucasian men; Drug: Placebo; Gender-effect in Caucasian women; Drug: Placebo; Single ascending dose in Japanese men
Placebo Comparator: Placebo: Age-effect in Caucasian men	Drug: Placebo; Single ascending dose in Caucasian men; Drug: Placebo; Age-effect in Caucasian men; Drug: Placebo; Gender-effect in Caucasian women; Drug: Placebo; Single ascending dose in Japanese men
Placebo Comparator: Placeo: Gender-effect in Caucasian women	Drug: Placebo; Single ascending dose in Caucasian men; Drug: Placebo; Age-effect in Caucasian men; Drug: Placebo; Gender-effect in Caucasian women; Drug: Placebo; Single ascending dose in Japanese men
Placebo Comparator: Placebo: Single ascending dose in Japanese men	Drug: Placebo; Single ascending dose in Caucasian men; Drug: Placebo; Age-effect in Caucasian men; Drug: Placebo; Gender-effect in Caucasian women; Drug: Placebo; Single ascending dose in Japanese men

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation
• Investigators: Principal Investigator: Steve Warrington, MA MD FRCP FFPM, Hammersmith Medicines Research

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: June 4, 2013
• First Submitted That Met QC Criteria: June 12, 2013
• First Posted (Estimate): June 17, 2013

Study Record Updates

• Last Update Posted (Estimate): June 17, 2013
• Last Update Submitted That Met QC Criteria: June 12, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Dyslipidemia; MT-8995; Cholesteryl ester transfer proteins
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias
• Other Study ID Numbers: TA-8995-01