Effect of AKB-6548 on Cardiac Repolarization Intervals in Healthy Volunteers

A Phase 1, Single-Center, Partially Double-Blinded, Active and Placebo Controlled, Randomized 4-Way Crossover Study to Evaluate the Effect of AKB-6548 on Cardiac Repolarization Intervals in Healthy Volunteers

The main purpose of this study is to evaluate the effect of single oral therapeutic and supratherapeutic doses of AKB-6548 on the QT interval.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Moxifloxacin; Drug: AKB-6548 (therapeutic dose); Drug: AKB-6548 (supratherapeutic dose)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Evansville, Indiana, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Healthy, non-smoking males or females, 18 and 55 years of age, inclusive
• BMI 18.0 and 32.0 kg/m2, inclusive
• non clinically significant 12-lead ECG
• heart rate of 45 to 90 beats per minute, inclusive
• mean systolic blood pressure <141 mmHg and mean diastolic blood pressure < 90 mmHg

Key Exclusion Criteria:

• history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, GI, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
• history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias, or torsades de pointes, structural heart disease, or a family history of Long QT syndrome
• significant abnormalities in liver function tests
• history of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs
• history of Gilbert's Syndrome
• positive hepatitis panel
• seizure disorder or receiving anti-epilepsy medication for seizure disorder
• any acute or chronic condition that, in the opinion of the Investigator, may pose a safety risk to a subject in this study or which would limit the subject's ability to complete and/or participate in this clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Single oral dose of placebo
ACTIVE_COMPARATOR: Moxifloxacin	Drug: Moxifloxacin; Single oral dose of 400 mg moxifloxacin
EXPERIMENTAL: AKB-6548 (therapeutic dose)	Drug: AKB-6548 (therapeutic dose); Single oral dose of AKB-6548 at a therapeutic dose level
EXPERIMENTAL: AKB-6548 (supratherapeutic dose)	Drug: AKB-6548 (supratherapeutic dose); Single oral dose of AKB-6548 at a supratherapeutic dose level

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Placebo-corrected change-from-baseline QTcF (ΔΔQTcF) following AKB-6548 administration.	multiple timepoint evaluations from pre-dose to 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Placebo-corrected change-from-baseline heart rate (HR), PR interval, QRS interval	multiple timepoint evaluations from pre-dose to 24 hours post-dose
Categorical outliers defined as QTcF >450 msec, 480 msec and 500 msec at any timepoint and change-from-baseline QTcF (ΔQTcF) >30 msec (increased by 30 msec) and >60 msec	multiple timepoint evaluations from pre-dose to 24 hours post-dose
Categorical outliers for HR, PR interval, QRS interval	multiple timepoint evaluations from pre-dose to 24 hours post-dose
Frequency of T wave morphology changes	multiple timepoint evaluations from pre-dose to 24 hours post-dose
Placebo-corrected change-from-baseline QTcF (ΔΔQTcF) following moxifloxacin administration	multiple timepoint evaluations from pre-dose to 24 hours post-dose
Safety parameters to include adverse events; changes in routine clinical laboratory measures including chemistry, hematology, and urinalysis; and clinically significant changes noted during physical examinations or in vital signs	from first dose of study medication through the final protocol required visit

Collaborators and Investigators

• Sponsor: Akebia Therapeutics

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ACTUAL): April 1, 2014
• Study Completion (ACTUAL): April 1, 2014

Study Registration Dates

• First Submitted: February 11, 2014
• First Submitted That Met QC Criteria: February 12, 2014
• First Posted (ESTIMATE): February 13, 2014

Study Record Updates

• Last Update Posted (ACTUAL): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 10, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: safety; anemia; chronic kidney disease; CKD; pharmacokinetic; renal impairment; QT interval; TQT; chronic renal insufficiency; Akebia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Glycine Agents; Moxifloxacin; Glycine
• Other Study ID Numbers: AKB-6548-CI-0010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED