Clinical trial NCT02062203: Effect of AKB-6548 on Cardiac Repolarization Intervals in Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Akebia
QT interval
TQT
pharmacokinetic
anemia
chronic kidney disease
CKD
chronic renal insufficiency
renal impairment
safety
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-02-13
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Placebo-corrected change-from-baseline QTcF (ΔΔQTcF) following AKB-6548 administration.
timeFrame: multiple timepoint evaluations from pre-dose to 24 hours post-dose
Secondary outcomes:
measure: Placebo-corrected change-from-baseline heart rate (HR), PR interval, QRS interval
timeFrame: multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: 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
timeFrame: multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Categorical outliers for HR, PR interval, QRS interval
timeFrame: multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Frequency of T wave morphology changes
timeFrame: multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: Placebo-corrected change-from-baseline QTcF (ΔΔQTcF) following moxifloxacin administration
timeFrame: multiple timepoint evaluations from pre-dose to 24 hours post-dose
measure: 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
timeFrame: from first dose of study medication through the final protocol required visit
Other outcomes:
Locations:
city: Evansville
country: United States
state: Indiana
Study officials:
affiliation: Sponsor GmbH
name: Akebia Therapeutics
role: STUDY_DIRECTOR
References: