This is a Phase 1, single-center, randomized, single-blind (participants are blinded), placebo controlled, four-way cross over TQT study (4×4 Williams square design) to investigate the effect of KP-001 on the QTc interval using open-label moxifloxacin as an active control, in adult healthy volunteers. KP-001 and placebo (dry syrup) will be administered in blinded manner to participants, and the moxifloxacin (tablet) will be administered in open-label manner.Total duration of study participation for each participant is approximately 8 weeks. Cardiodynamic ECG evaluations will be performed at separate locations and cardiodynamic ECG evaluators will be blinded to treatment group analyzed, ie, blinded to each of the study interventions including moxifloxacin.
This is a Phase 1, single-center, randomized, single-blind (participants are blinded), placebo controlled, four-way cross over TQT study (4×4 Williams square design) to investigate the effect of KP-001 on the QTc interval using open-label moxifloxacin as an active control, in adult healthy volunteers. KP-001 and placebo (dry syrup) will be administered in blinded manner to participants, and the moxifloxacin (tablet) will be administered in open-label manner. The study will comprise the following: * Treatment Periods 1, 2, 3, and 4: For each period, participants will be residential at the Clinical Unit from the day before the dose of study intervention (Day 1 of each treatment period) until 3 days after the dose of study intervention (Day 4 of each treatment period). Participants will receive a single dose of study intervention each period, in accordance with the assigned treatment sequence . * Washout: at least 7 days between administrations of each study intervention. Total duration of study participation for each participant is approximately 8 weeks. On Day 1 of Treatment Period 1, participants will be randomly assigned in a 1:1:1:1 ratio to one of the four treatment sequences and administrated a single oral dose of one of the following four treatments under fasting condition: * KP-001 therapeutic dose (T): KP-001 100 mg + placebo * KP-001 supratherapeutic dose (ST): KP-001 400 mg * Placebo (P): placebo dry syrup * Moxifloxacin (M): moxifloxacin 400 mg tablet Cardiodynamic ECG evaluations will be performed at separate locations and cardiodynamic ECG evaluators will be blinded to treatment group analyzed, ie, blinded to each of the study interventions including moxifloxacin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
40
Parexel Early Phase Clinical Unit - Los Angeles
Glendale, California, United States
Largest time-matched placebo-corrected change from baseline in QTcF (ΔΔQTcF) collected in a 24-hour period after KP-001 single dosing
To evaluate the effect of KP-001 as single therapeutic and supratherapeutic dose on the QTcF interval
Time frame: Before dosing (Baseline) through 24 hours
Placebo-corrected change from baseline in QTcF (ΔΔQTcF)
To study the concentration-response relationship between KP-001 concentrations after dosing and ΔQTcF (C-ΔQTcF model)
Time frame: Before dosing (Baseline) through 24 hours
Largest time-matched placebo-corrected change from baseline in QTcF (ΔΔQTcF) after moxifloxacin dosing
Largest time-matched placebo-corrected change from baseline in QTcF (ΔΔQTcF) collected in a 24-hour period after moxifloxacin dosing
Time frame: Before dosing (Baseline) through 24 hours
Categorial outliers for QRS after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
Placebo-corrected ΔHR after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
Placebo-corrected ΔPR after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
Placebo-corrected ΔQRS after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
Categorial outliers for PR after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
Categorial outliers for HR after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
Categorial outliers for QTcF after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
Change from baseline PR after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
Change from baseline HR after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
PK parameters of KP-001 in plasma: CLtot/F
Time frame: pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 36 and 72 hours post-dose
PK parameters of KP-001 in plasma: Tmax
To evaluate PK of KP-001
Time frame: pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
PK parameters of KP-001 in plasma: t1/2
To evaluate PK of KP-001
Time frame: pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
PK parameters of KP-001 in plasma: Vz/F
To evaluate PK of KP-001
Time frame: pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
Frequency of treatment-emergent morphology and appearance of U-wave after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
PK parameters of KP-001 in plasma: Cmax
To evaluate PK of KP-001
Time frame: pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
Frequency of treatment-emergent changes in Twave morphology after KP-001 dosing
Time frame: Before dosing (Baseline) through 24 hours
PK parameters of KP-001 in plasma: AUC0-24
Time frame: pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
PK parameters of KP-001 in plasma: AUC0-48
Time frame: pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
PK parameters of KP-001 in plasma: AUC0-72
Time frame: pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
PK parameters of KP-001 in plasma: AUCinf
Area Under the Concentration Time-curve From Time Zero to Infinity for KP-001
Time frame: pre-dose and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
Placebo-corrected change from baseline in QTcF (ΔΔQTcF) predicted from the C-ΔQTcF model at Cmax
To study the concentration-response relationship between KP-001 concentrations
Time frame: Before dosing (Baseline) through 24 hours
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