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

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.

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.

Study Overview

• Status: Completed
• Conditions: Dyslipidemia; Healthy Volunteers
• Intervention / Treatment: Drug: TAP311

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miramar, Florida, United States, 33025
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CTAP311X2101 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: November 28, 2011
• First Submitted That Met QC Criteria: December 5, 2011
• First Posted (Estimate): December 7, 2011

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Hyperlipidemia; Simvastatin; High cholesterol levels; High-density Lipoprotein; Low-density Lipoprotein
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias
• Other Study ID Numbers: CTAP311X2101