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

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

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

Study Overview

• Status: Completed
• Conditions: Dyslipidemia
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, 22769
    • Momentum Pharma Services GmbH

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TA-8995 1 mg	Drug: TA-8995; Drug: TA-8995 1mg; Drug: TA-8995; Drug: TA-8995 2.5mg; Drug: TA-8995; Drug: TA-8995 5mg; Drug: TA-8995; Drug: TA-8995 10mg; Drug: TA-8995; Drug: TA-8995 25mg
Experimental: TA-8995 2.5 mg	Drug: TA-8995; Drug: TA-8995 1mg; Drug: TA-8995; Drug: TA-8995 2.5mg; Drug: TA-8995; Drug: TA-8995 5mg; Drug: TA-8995; Drug: TA-8995 10mg; Drug: TA-8995; Drug: TA-8995 25mg
Experimental: TA-8995 5 mg	Drug: TA-8995; Drug: TA-8995 1mg; Drug: TA-8995; Drug: TA-8995 2.5mg; Drug: TA-8995; Drug: TA-8995 5mg; Drug: TA-8995; Drug: TA-8995 10mg; Drug: TA-8995; Drug: TA-8995 25mg
Experimental: TA-8995 10 mg	Drug: TA-8995; Drug: TA-8995 1mg; Drug: TA-8995; Drug: TA-8995 2.5mg; Drug: TA-8995; Drug: TA-8995 5mg; Drug: TA-8995; Drug: TA-8995 10mg; Drug: TA-8995; Drug: TA-8995 25mg
Experimental: TA-8995 25 mg	Drug: TA-8995; Drug: TA-8995 1mg; Drug: TA-8995; Drug: TA-8995 2.5mg; Drug: TA-8995; Drug: TA-8995 5mg; Drug: TA-8995; Drug: TA-8995 10mg; Drug: TA-8995; Drug: TA-8995 25mg
Placebo Comparator: Placebo (TA-8995 1mg)	Drug: Placebo; Placebo (TA-8995 1mg); Drug: Placebo; Placebo (TA-8995 2.5mg); Drug: Placebo; Placebo (TA-8995 5mg); Drug: Placebo; Placebo (TA-8995 10mg); Drug: Placebo; Placebo (TA-8995 25mg)
Placebo Comparator: Placebo (TA-8995 2.5mg)	Drug: Placebo; Placebo (TA-8995 1mg); Drug: Placebo; Placebo (TA-8995 2.5mg); Drug: Placebo; Placebo (TA-8995 5mg); Drug: Placebo; Placebo (TA-8995 10mg); Drug: Placebo; Placebo (TA-8995 25mg)
Placebo Comparator: Placebo (TA-8995 5mg)	Drug: Placebo; Placebo (TA-8995 1mg); Drug: Placebo; Placebo (TA-8995 2.5mg); Drug: Placebo; Placebo (TA-8995 5mg); Drug: Placebo; Placebo (TA-8995 10mg); Drug: Placebo; Placebo (TA-8995 25mg)
Placebo Comparator: Placebo (TA-8995 10mg)	Drug: Placebo; Placebo (TA-8995 1mg); Drug: Placebo; Placebo (TA-8995 2.5mg); Drug: Placebo; Placebo (TA-8995 5mg); Drug: Placebo; Placebo (TA-8995 10mg); Drug: Placebo; Placebo (TA-8995 25mg)
Placebo Comparator: Placebo (TA-8995 25mg)	Drug: Placebo; Placebo (TA-8995 1mg); Drug: Placebo; Placebo (TA-8995 2.5mg); Drug: Placebo; Placebo (TA-8995 5mg); Drug: Placebo; Placebo (TA-8995 10mg); Drug: Placebo; Placebo (TA-8995 25mg)

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
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	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

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation
• Investigators: Principal Investigator: Werner Weber, MD, Momentum Pharma Services GmbH

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

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-E02