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

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: AKB-6548 (therapeutic dose); Drug: Placebo; Drug: AKB-6548 (supratherapeutic dose); Drug: Moxifloxacin

• Registration Number: NCT02062203
• Lead Sponsor: Akebia Therapeutics

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-02-11
• Study First Submitted QC: 2014-02-12
• Study First Posted: 2014-02-13
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-10
• Last Update Posted: 2018-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
AKB-6548 (therapeutic dose)	AKB-6548 (therapeutic dose)	-
Placebo	Placebo	-
AKB-6548 (supratherapeutic dose)	AKB-6548 (supratherapeutic dose)	-
Moxifloxacin	Moxifloxacin	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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