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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: AKB-6548 (therapeutic dose)
* Drug: AKB-6548 (supratherapeutic dose)
* Drug: Placebo
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKB-6548 (therapeutic dose)<br> | Drug: AKB-6548 (therapeutic dose)<br>* Single oral dose of AKB-6548 at a therapeutic dose level<br>|
| Experimental: AKB-6548 (supratherapeutic dose)<br> | Drug: AKB-6548 (supratherapeutic dose)<br>* Single oral dose of AKB-6548 at a supratherapeutic dose level<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Single oral dose of placebo<br>|
| Active Comparator: Moxifloxacin<br> | Drug: Moxifloxacin<br>* Single oral dose of 400 mg moxifloxacin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anemia, TQT, Akebia, QT interval, pharmacokinetic, chronic kidney disease, CKD, chronic renal insufficiency, renal impairment, safety