Trial Outcomes & Findings for Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2). (NCT NCT05906732)
NCT ID: NCT05906732
Last Updated: 2025-07-24
Results Overview
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
42 participants
Primary outcome timeframe
2.0 hours after administration of study treatment on Day 4.
Results posted on
2025-07-24
Participant Flow
Participant milestones
| Measure |
Part 1: Arm A: Dofetilide With Dose-escalating LQT-1213 TID Followed by Dofetilide With Placebo
Dofetilide 500 μg BID (Days 1-8) and LQT-1213 TID 0.25 mg/kg (Days 3 and 4), 0.50 mg/kg (Days 5 and 6), and 0.70 mg/kg on Days 7 and 8. After adequate washout, Dofetilide 500 μg BID (Days 1-8) and placebo (Days 3-8).
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
Dofetilide 250 μg Cap: Dofetilide is a potent, pure inward-rectifier potassium channels (IKr) blocker
|
Part 1: Arm B: Dofetilide With Placebo Followed by Dofetilide With LQT-1213 TID
Dofetilide 500 μg BID, orally (Days 1-8) and placebo matched to LQT-1213 TID (Days 3-8). After adequate washout, Dofetilide 500 μg BID, orally (Days 1-8) and LQT-1213 3 times a day (TID) 0.25 mg/kg (Days 3 and 4), 0.50 mg/kg (Days 5 and 6), and 0.70 mg/kg on Days 7 and 8.
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
Dofetilide 250 μg Cap: Dofetilide is a potent, pure inward-rectifier potassium channels (IKr) blocker
|
Part 2: TID Dosing of LQT-1213 16 mg (48 mg Daily)
LQT-1213 16 mg TID (at time 0, 8 and 16 hours) on Days 2-4, with a final single morning dose on Day 4. Day 1 was placebo.
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
|
Part 2: TID Dosing of LQT-1213 7 mg (21 mg Daily)
LQT-1213 7 mg TID (at time 0, 8 and 16 hours) on Days 2-4, with a final single morning dose on Day 4. Day 1 was placebo.
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
6
|
6
|
|
Overall Study
COMPLETED
|
12
|
11
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
0
|
0
|
Reasons for withdrawal
| Measure |
Part 1: Arm A: Dofetilide With Dose-escalating LQT-1213 TID Followed by Dofetilide With Placebo
Dofetilide 500 μg BID (Days 1-8) and LQT-1213 TID 0.25 mg/kg (Days 3 and 4), 0.50 mg/kg (Days 5 and 6), and 0.70 mg/kg on Days 7 and 8. After adequate washout, Dofetilide 500 μg BID (Days 1-8) and placebo (Days 3-8).
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
Dofetilide 250 μg Cap: Dofetilide is a potent, pure inward-rectifier potassium channels (IKr) blocker
|
Part 1: Arm B: Dofetilide With Placebo Followed by Dofetilide With LQT-1213 TID
Dofetilide 500 μg BID, orally (Days 1-8) and placebo matched to LQT-1213 TID (Days 3-8). After adequate washout, Dofetilide 500 μg BID, orally (Days 1-8) and LQT-1213 3 times a day (TID) 0.25 mg/kg (Days 3 and 4), 0.50 mg/kg (Days 5 and 6), and 0.70 mg/kg on Days 7 and 8.
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
Dofetilide 250 μg Cap: Dofetilide is a potent, pure inward-rectifier potassium channels (IKr) blocker
|
Part 2: TID Dosing of LQT-1213 16 mg (48 mg Daily)
LQT-1213 16 mg TID (at time 0, 8 and 16 hours) on Days 2-4, with a final single morning dose on Day 4. Day 1 was placebo.
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
|
Part 2: TID Dosing of LQT-1213 7 mg (21 mg Daily)
LQT-1213 7 mg TID (at time 0, 8 and 16 hours) on Days 2-4, with a final single morning dose on Day 4. Day 1 was placebo.
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
|
Overall Study
Physician Decision
|
2
|
4
|
0
|
0
|
Baseline Characteristics
Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
Baseline characteristics by cohort
| Measure |
Part 1: Arm A: Dofetilide With Dose-escalating LQT-1213 TID Followed by Dofetilide With Placebo
n=15 Participants
Dofetilide 500 μg BID (Days 1-8) and LQT-1213 TID 0.25 mg/kg (Days 3 and 4), 0.50 mg/kg (Days 5 and 6), and 0.70 mg/kg on Days 7 and 8. After adequate washout, Dofetilide 500 μg BID (Days 1-8) and placebo (Days 3-8).
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
Dofetilide 250 μg Cap: Dofetilide is a potent, pure inward-rectifier potassium channels (IKr) blocker
|
Part 1: Arm B: Dofetilide With Placebo Followed by Dofetilide With LQT-1213 TID
n=15 Participants
Dofetilide 500 μg BID, orally (Days 1-8) and placebo matched to LQT-1213 TID (Days 3-8). After adequate washout, Dofetilide 500 μg BID, orally (Days 1-8) and LQT-1213 3 times a day (TID) 0.25 mg/kg (Days 3 and 4), 0.50 mg/kg (Days 5 and 6), and 0.70 mg/kg on Days 7 and 8.
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
Dofetilide 250 μg Cap: Dofetilide is a potent, pure inward-rectifier potassium channels (IKr) blocker
|
Part 2: TID Dosing of LQT-1213 16 mg
n=6 Participants
LQT-1213 16 mg TID (at time 0, 8 and 16 hours) on Days 2-4, with a final single morning dose on Day 4. Day 1 was placebo.
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
|
Part 2: TID Dosing of LQT-1213 7mg
n=6 Participants
LQT-1213 7 mg TID (at time 0, 8 and 16 hours) on Days 2-4, with a final single morning dose on Day 4. Day 1 was placebo.
LQT-1213: LQT-1213 is a serum glucocorticoid regulated kinase 1 (SGK-1) inhibitor
Placebo: Matching Placebo
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
43.3 years
STANDARD_DEVIATION 12.4 • n=5 Participants
|
42.2 years
STANDARD_DEVIATION 9.13 • n=7 Participants
|
42.0 years
STANDARD_DEVIATION 13.71 • n=5 Participants
|
40.3 years
STANDARD_DEVIATION 8.33 • n=4 Participants
|
42 years
STANDARD_DEVIATION 10.84 • n=21 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
14 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
body mass index
|
27.35 kg/m2
STANDARD_DEVIATION 3.365 • n=5 Participants
|
26.99 kg/m2
STANDARD_DEVIATION 2.942 • n=7 Participants
|
30.82 kg/m2
STANDARD_DEVIATION 6.971 • n=5 Participants
|
33.33 kg/m2
STANDARD_DEVIATION 7.560 • n=4 Participants
|
28.57 kg/m2
STANDARD_DEVIATION 4.33 • n=21 Participants
|
PRIMARY outcome
Timeframe: 2.0 hours after administration of study treatment on Day 4.Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=28 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
40.8 msec
Standard Error 11.08
|
50.3 msec
Standard Error 14.77
|
—
|
—
|
PRIMARY outcome
Timeframe: 2.5 hours after administration of study treatment on Day 4Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=27 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=28 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
43.3 msec
Standard Error 11.76
|
48.0 msec
Standard Error 11.42
|
—
|
—
|
PRIMARY outcome
Timeframe: 3.0 hours after administration of study treatment on Day 4Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=28 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
40.9 msec
Standard Error 11.05
|
48.6 msec
Standard Error 12.93
|
—
|
—
|
PRIMARY outcome
Timeframe: 3.5 hours after administration of study treatment on Day 4Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=28 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=28 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
43.4 msec
Standard Error 13.01
|
46.4 msec
Standard Error 11.33
|
—
|
—
|
PRIMARY outcome
Timeframe: 4.0 hours after administration of study treatment on Day 4Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=28 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
39.2 msec
Standard Error 10.85
|
43.3 msec
Standard Error 13.83
|
—
|
—
|
PRIMARY outcome
Timeframe: 2.0 hours after administration of study treatment on Day 6Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=23 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
42.4 msec
Standard Error 15.89
|
43.9 msec
Standard Error 16.41
|
—
|
—
|
PRIMARY outcome
Timeframe: 2.5 hours after administration of study treatment on Day 6Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=23 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=26 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
43.7 msec
Standard Error 14.74
|
42.5 msec
Standard Error 16.93
|
—
|
—
|
PRIMARY outcome
Timeframe: 3.0 hours after administration of study treatment on Day 6Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=23 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=24 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
42.3 msec
Standard Error 12.57
|
40.4 msec
Standard Error 16.70
|
—
|
—
|
PRIMARY outcome
Timeframe: 3.5 hours after administration of study treatment on Day 6Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=23 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=24 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
42.0 msec
Standard Error 13.40
|
40.7 msec
Standard Error 15.45
|
—
|
—
|
PRIMARY outcome
Timeframe: 4.0 hours after administration of study treatment on Day 6Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=24 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=27 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
38.5 msec
Standard Error 14.64
|
35.3 msec
Standard Error 17.14
|
—
|
—
|
PRIMARY outcome
Timeframe: 2.0 hours after administration of study treatment on Day 8Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=23 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=27 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
45.0 msec
Standard Error 14.31
|
48.9 msec
Standard Error 13.94
|
—
|
—
|
PRIMARY outcome
Timeframe: 2.5 hours after administration of study treatment on Day 8Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=24 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
46.6 msec
Standard Error 14.23
|
46.8 msec
Standard Error 11.45
|
—
|
—
|
PRIMARY outcome
Timeframe: 3.0 hours after administration of study treatment on Day 8Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=24 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
46.4 msec
Standard Error 15.18
|
48.0 msec
Standard Error 13.24
|
—
|
—
|
PRIMARY outcome
Timeframe: 3.5 hours after administration of study treatment on Day 8Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=24 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=26 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
44.4 msec
Standard Error 13.84
|
48.3 msec
Standard Error 12.34
|
—
|
—
|
PRIMARY outcome
Timeframe: 4.0 hours after administration of study treatment on Day 8Population: All subjects who received at least 1 dose of any study treatment (dofetilide, LQT-1213, or placebo) and had measurements at baseline as well as on-treatment with at least 1 post-baseline time point with a ΔQTc value.
The primary outcome is time-based comparison in the change from baseline (baseline defined as Day 1 of Period 1 and Day 1 of Period 2 mean predose QTc) ΔΔQTc by Fridericia's formula (QTcF) during peak dofetilide exposure between dofetilide and placebo treatment, and the dofetilide and LQT-1213 treatment.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=23 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacodynamics: By-time Point Analysis for QTc on LQT-1213 Versus Placebo
|
—
|
—
|
41.4 msec
Standard Error 12.25
|
45.7 msec
Standard Error 11.75
|
—
|
—
|
PRIMARY outcome
Timeframe: up to day 12Population: all participants with LQT2, or LQT3 who received at least 1 dose of study drug (placebo or LQT-1213) and provide at least 1 postdose safety assessment.
The primary outcome is to measure the incidence of treatment emergent adverse events (TEAEs).
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
n=6 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Safety and Tolerability of Oral LQT-1213 in Participants With LQT-2 or LQT-3
|
—
|
1 TEAE
|
4 TEAE
|
3 TEAE
|
2 TEAE
|
—
|
SECONDARY outcome
Timeframe: 0 to 24 hours post-dose on Day 8Population: The overall number of participants analyzed for PK parameters includes all individuals who had available the PK parameter, regardless of whether this data was collected in Period 1 or Period 2 of the two sequences described in the participant Flow.
Area under the concentration-time curve (AUC) from time 0 to the time of the last measurable concentration
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacokinetic LQT-1213 AUC0-t
|
—
|
—
|
13221.182 h*ng/ml
Geometric Coefficient of Variation 47.6
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 to 24 hours post-dose on Day 8Area under the concentration-time curve (AUC) from time 0 to the time of the last measurable concentration
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacokinetic Dofetilide AUC0-t
|
—
|
—
|
50.160 h*ng/ml
Geometric Coefficient of Variation 18.6
|
51.863 h*ng/ml
Geometric Coefficient of Variation 17.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 4,6, 8Population: pk population= at least 1 evaluable PK concentration for dofetilide or LQT-1213
AUCtau = Area under the curve from time 0 to 8.0 hours
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacokinetic LQT-1213 AUCtau
|
—
|
8763.318 h*ng/ml
Geometric Coefficient of Variation 48.0
|
2735.793 h*ng/ml
Geometric Coefficient of Variation 47.9
|
5433.729 h*ng/ml
Geometric Coefficient of Variation 49.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 4,6,8Population: The overall number of participants analyzed for PK parameters includes all individuals who had available the PK parameter, regardless of whether this data was collected in Period 1 or Period 2 of the two sequences described in the participant Flow.
AUCtau = Area under the curve from time 0 to 12 hours
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
n=25 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
n=29 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
n=25 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacokinetic Dofetilide AUCtau
|
36.390 h*ng/ml
Geometric Coefficient of Variation 16.6
|
37.075 h*ng/ml
Geometric Coefficient of Variation 16.0
|
36.350 h*ng/ml
Geometric Coefficient of Variation 17.3
|
35.916 h*ng/ml
Geometric Coefficient of Variation 15.3
|
35.142 h*ng/ml
Geometric Coefficient of Variation 18.4
|
38.227 h*ng/ml
Geometric Coefficient of Variation 15.3
|
SECONDARY outcome
Timeframe: Day 4,6,8Maximum observed plasma drug concentration
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacokinetic LQT-1213 Cmax
|
—
|
1612.274 ng/ml
Geometric Coefficient of Variation 48.5
|
501.739 ng/ml
Geometric Coefficient of Variation 48.0
|
1013.942 ng/ml
Geometric Coefficient of Variation 52.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 4,6, 8Population: The overall number of participants analyzed for PK parameters includes all individuals who had available the PK parameter, regardless of whether this data was collected in Period 1 or Period 2 of the two sequences described in the participant Flow.
Maximum observed plasma drug concentration
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
n=25 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
n=29 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
n=25 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacokinetic Dofetilide Cmax
|
4.438 ng/ml
Geometric Coefficient of Variation 19.6
|
4.580 ng/ml
Geometric Coefficient of Variation 16.8
|
4.367 ng/ml
Geometric Coefficient of Variation 18.7
|
4.394 ng/ml
Geometric Coefficient of Variation 16.9
|
4.184 ng/ml
Geometric Coefficient of Variation 19.0
|
4.727 ng/ml
Geometric Coefficient of Variation 20.6
|
SECONDARY outcome
Timeframe: Day 4,6,8Time to the maximum observed plasma concentration
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacokinetic LQT-1213 Tmax
|
—
|
1.999 hours
Interval 0.99 to 5.05
|
1.012 hours
Interval 0.98 to 6.0
|
1.114 hours
Interval 0.98 to 5.06
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 4,6,8Population: The overall number of participants analyzed for PK parameters includes all individuals who had available the PK parameter, regardless of whether this data was collected in Period 1 or Period 2 of the two sequences described in the participant Flow.
Time to the maximum observed plasma concentration
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
n=25 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
n=29 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
n=25 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacokinetic Dofetilide Tmax
|
2.008 hours
Interval 1.0 to 5.51
|
2.017 hours
Interval 1.0 to 4.01
|
2.012 hours
Interval 1.0 to 6.0
|
2.003 hours
Interval 1.0 to 3.52
|
2.015 hours
Interval 1.0 to 451.0
|
2.504 hours
Interval 1.01 to 4.02
|
SECONDARY outcome
Timeframe: Day 8Terminal half-life
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacokinetic LQT-1213 t1/2
|
—
|
—
|
8.374 hours
Geometric Coefficient of Variation 22.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 8Terminal half-life
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=25 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Pharmacokinetic Dofetilide t1/2
|
—
|
—
|
7.139 hours
Geometric Coefficient of Variation 16.2
|
7.341 hours
Geometric Coefficient of Variation 14.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Period 1 from Day 1 to Day 10 and Period 2 from Day 1 up to Day 17.Part 1: Number of Treatment Emerging Adverse Events (TEAEs) that occurred following administration of dofetilide Day1 up to Day 10 period 1 and in period 2 from Day 1 to up to the follow-up visit at Day 17.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
n=29 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=30 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=29 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
n=25 Participants
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 1: Number of Treatment Emerging Adverse Events (TEAEs)
|
25 TEAE
|
12 TEAE
|
12 TEAE
|
6 TEAE
|
1 TEAE
|
—
|
SECONDARY outcome
Timeframe: Day 4 Pre-dose up to 29 hours post-dose administrationArea under the concentration-time curve (AUC) from time 0 to the time of the last measurable concentration
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Pharmacokinetic LQT-1213 AUC0-t
|
—
|
—
|
5968 h*ng/ml
Geometric Coefficient of Variation 30.9
|
2109 h*ng/ml
Geometric Coefficient of Variation 19.5
|
—
|
—
|
SECONDARY outcome
Timeframe: day 2 and day 4Pharmacokinetic LQT-1213 AUCtau (time 0 to 8 hours)
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Pharmacokinetic LQT-1213 AUCtau
Day 2
|
—
|
—
|
2214 h*ng/ml
Geometric Coefficient of Variation 41.7
|
635.3 h*ng/ml
Geometric Coefficient of Variation 22.8
|
—
|
—
|
|
Part 2: Pharmacokinetic LQT-1213 AUCtau
Day 4
|
—
|
—
|
3314 h*ng/ml
Geometric Coefficient of Variation 32.3
|
1153 h*ng/ml
Geometric Coefficient of Variation 28.0
|
—
|
—
|
SECONDARY outcome
Timeframe: day 2 and day 4Maximum observed plasma drug concentration
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Pharmacokinetic LQT-1213 Cmax
Day 2
|
—
|
—
|
470.9 ng/ml
Geometric Coefficient of Variation 46.5
|
116.4 ng/ml
Geometric Coefficient of Variation 23.8
|
—
|
—
|
|
Part 2: Pharmacokinetic LQT-1213 Cmax
Day 4
|
—
|
—
|
562.9 ng/ml
Geometric Coefficient of Variation 44.4
|
195.1 ng/ml
Geometric Coefficient of Variation 33.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 2 and Day 4Time to the maximum observed plasma concentration
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Pharmacokinetic LQT-1213 Tmax
Day 2
|
—
|
—
|
1.523 ng/ml
Interval 1.01 to 4.01
|
1.268 ng/ml
Interval 1.0 to 2.01
|
—
|
—
|
|
Part 2: Pharmacokinetic LQT-1213 Tmax
Day 4
|
—
|
—
|
1.534 ng/ml
Interval 0.98 to 4.01
|
1.781 ng/ml
Interval 1.02 to 5.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 4Part 2: Pharmacokinetic LQT-1213 terminal half-life t1/2
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Pharmacokinetic LQT-1213 t1/2
|
—
|
—
|
11.97 hours
Geometric Coefficient of Variation 11.8
|
9.982 hours
Geometric Coefficient of Variation 9.8
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 hour after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF - 1 Hour Post Dose
|
—
|
—
|
519.17 msec
Standard Deviation 32.344
|
514.89 msec
Standard Deviation 29.569
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Day 4 were compared to the time-matched QTcF value on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 2 Hours Post-dose
|
—
|
—
|
520.06 msec
Standard Deviation 31.231
|
513.28 msec
Standard Deviation 23.733
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 3 Hours Post-dose
|
—
|
—
|
513.94 msec
Standard Deviation 26.410
|
530.00 msec
Standard Deviation 39.838
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 4 Hours Post-dose
|
—
|
—
|
514.61 msec
Standard Deviation 28.450
|
523.67 msec
Standard Deviation 32.158
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 6 Hours Post-dose
|
—
|
—
|
520.89 msec
Standard Deviation 26.741
|
531.56 msec
Standard Deviation 32.897
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 8 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 8 Hours Post-dose
|
—
|
—
|
503.61 msec
Standard Deviation 22.106
|
507.61 msec
Standard Deviation 23.640
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 10 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 10 Hours Post-dose
|
—
|
—
|
521.00 msec
Standard Deviation 9.78
|
511.22 msec
Standard Deviation 22.872
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 12 Hours Post-dose
|
—
|
—
|
519.42 msec
Standard Deviation 26.753
|
522.11 msec
Standard Deviation 23.167
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 1 Hour Post-dose (Low Dose)
|
—
|
—
|
524.39 msec
Standard Deviation 29.611
|
521.22 msec
Standard Deviation 33.791
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 2 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 2 Hours Post-dose (Low Dose)
|
—
|
—
|
531.72 msec
Standard Deviation 38.880
|
525.94 msec
Standard Deviation 29.837
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test, which was the same as analyzing the difference of the time-matched QTcF values using one-sample t test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 3 Hours Post-dose (Low Dose)
|
—
|
—
|
538.22 msec
Standard Deviation 38.584
|
523.06 msec
Standard Deviation 33.857
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 4 Hours Post-dose (Low Dose)
|
—
|
—
|
535.72 msec
Standard Deviation 34.812
|
522.17 msec
Standard Deviation 35.036
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 6 Hours Post-dose (Low Dose)
|
—
|
—
|
530.67 msec
Standard Deviation 43.213
|
530.17 msec
Standard Deviation 32.590
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 8 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 8 Hours Post-dose (Low Dose)
|
—
|
—
|
522.67 msec
Standard Deviation 33.363
|
516.94 msec
Standard Deviation 51.848
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 10 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 10 Hours Post-dose (Low Dose)
|
—
|
—
|
530.39 msec
Standard Deviation 40.667
|
514.78 msec
Standard Deviation 38.749
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 hours after administration of study treatment on Day 4.QTcF values at each timepoint on Days 4 were compared to the time-matched QTcF values on Day 1 (placebo) using the paired t-test.
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: Time-matched Placebo-corrected QTcF at 12 Hours Post-dose (Low Dose)
|
—
|
—
|
536.11 msec
Standard Deviation 44.465
|
518.89 msec
Standard Deviation 39.724
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (2 to 6 hours; LQT-1213) was compared to QTcF AUC on Day 1 (2 to 6 hours; placebo).
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC2-6 Hours QTcF Values on Day 4 (LQT-1213 16 mg TID) Compared to the Time-matched on Day 1 (Placebo)
|
—
|
—
|
2103.69 msec*hour
Standard Deviation 130.872
|
2066.69 msec*hour
Standard Deviation 113.850
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (3 to 6 hours; LQT-1213) was compared to QTcF AUC on Day 1 (3 to 6 hours; placebo).
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC3-6 Hours QTcF Values on Day 4 (LQT-1213 16 mg TID) Compared to the Time-matched on Day 1 (Placebo)
|
—
|
—
|
1582.06 msec*hour
Standard Deviation 100.213
|
1549.69 msec*hour
Standard Deviation 85.553
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (0 to 8 hours; LQT-1213) was compared to QTcF AUC on Day 1 (0 to 8 hours; placebo).
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC0-8 Hours QTcF Values on Day 4 (LQT-1213 16 mg TID) Compared to the Time-matched on Day 1 (Placebo)
|
—
|
—
|
4173.19 msec*hour
Standard Deviation 236.787
|
4128.64 msec*hour
Standard Deviation 224.746
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (0 to 12 hours; LQT-1213) was compared to QTcF AUC on Day 1 (0 to 12 hours; placebo).
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC0-12 Hours QTcF Values on Day 4 (LQT-1213 16 mg TID) Compared to the Time-matched on Day 1 (Placebo)
|
—
|
—
|
6225.35 msec*hour
Standard Deviation 323.651
|
6193.67 msec*hour
Standard Deviation 314.325
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (2 to 6 hours; LQT-1213) was compared to QTcF AUC on Day 1 (2 to 6 hours; placebo).
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC2-6 Hours QTcF Values on Day 4 (LQT-1213 7 mg TID) Compared to the Time-matched on Day 1 (Placebo)
|
—
|
—
|
2099.44 msec*hour
Standard Deviation 132.566
|
2137.25 msec*hour
Standard Deviation 150.766
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (3 to 6 hours; LQT-1213) was compared to QTcF AUC on Day 1 (3 to 6 hours; placebo).
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC3-6 Hours QTcF Values on Day 4 (LQT-1213 7 mg TID) Compared to the Time-matched on Day 1 (Placebo)
|
—
|
—
|
1574.94 msec*hour
Standard Deviation 101.583
|
1602.28 msec*hour
Standard Deviation 112.284
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (0 to 8 hours; LQT-1213) was compared to QTcF AUC on Day 1 (0 to 8 hours; placebo).
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC0-8 Hours QTcF Values on Day 4 (LQT-1213 7 mg TID) Compared to the Time-matched on Day 1 (Placebo)
|
—
|
—
|
4192.47 msec*hour
Standard Deviation 279.304
|
4248.69 msec*hour
Standard Deviation 290.144
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (0 to 12 hours; LQT-1213) was compared to QTcF AUC on Day 1 (0 to 12 hours; placebo).
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=6 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC0-12 Hours QTcF Values on Day 4 (LQT-1213 7 mg TID) Compared to the Time-matched on Day 1 (Placebo)
|
—
|
—
|
6257.86 msec*hour
Standard Deviation 445.699
|
6368.25 msec*hour
Standard Deviation 444.031
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (2 to 6 hours; LQT-1213) was compared to QTcF AUC on Day 1 (2 to 6 hours; placebo) for subjects with a Day 1 Pre-Dose (Baseline 1) QTcF \>= 500 ms
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=4 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=4 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC2-6 Hours QTcF Values on Day 4 (LQT-1213 16 mg TID) Compared to the Time-matched on Day 1 (Placebo) Subgroup Analysis (≥ 500ms)
|
—
|
—
|
2175.83 msec*hour
Standard Deviation 85.532
|
2131.54 msec*hour
Standard Deviation 69.025
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (3 to 6 hours; LQT-1213) was compared to QTcF AUC on Day 1 (3 to 6 hours; placebo) for subjects with a Day 1 Pre-Dose (Baseline 1) QTcF \>= 500 ms
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=4 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=4 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC3-6 Hours QTcF Values on Day 4 (LQT-1213 16 mg TID) Compared to the Time-matched on Day 1 (Placebo) Subgroup Analysis (≥ 500ms)
|
—
|
—
|
1636.33 msec*hour
Standard Deviation 68.013
|
1598.46 msec*hour
Standard Deviation 51.804
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (0 to 8 hours; LQT-1213) was compared to QTcF AUC on Day 1 (0 to 8 hours; placebo) for subjects with a Day 1 Pre-Dose (Baseline 1) QTcF \>= 500 ms
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=4 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=4 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC0-8 Hours QTcF Values on Day 4 (LQT-1213 16 mg TID) Compared to the Time-matched on Day 1 (Placebo) Subgroup Analysis (≥ 500ms)
|
—
|
—
|
4308.79 msec*hour
Standard Deviation 135.627
|
4255.38 msec*hour
Standard Deviation 138.707
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 4QTcF area under the curve on Day 4 (0 to 12 hours; LQT-1213) was compared to QTcF AUC on Day 1 (0 to 12 hours; placebo) for subjects with a Day 1 Pre-Dose (Baseline 1) QTcF \>= 500 ms
Outcome measures
| Measure |
Dofetilide + LQT-1213 (Day 6)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
LQT-1213 0.70 mg/kg (Day 8) TID
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) and LQT-1213 three times a day (TID) 0.25 mg/kg (Days 3 and 4), mid dose (Days 5 and 6) 0.50 mg/kg and high dose (Days 7 and 8) 0.70 mg/kg.
|
Dofetilide 500 μg (Day 4)
n=4 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide 500 μg (Day 6)
n=4 Participants
Dofetilide 500 μg twice a day (BID) orally (Days 1-8) combined to placebo.
|
Dofetilide + LQT-1213 (Day 4)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8.
|
Dofetilide + LQT-1213 (Day 8)
Dofetilide 500 µg twice daily (BID) orally on Days 1-8 and LQT-1213 3 times a day (TID) (0, 7.75, and 17 hours) orally on Days 3-8 as low dose (0.25 mg/kg) on Day 3 through the second dose on Day 4, mid dose (0.50 mg/kg) for last dose on Day 4 through the second dose on Day 6, and high dose (0.70 mg/kg) for last dose on Day 6 through the dose on Day 8
|
|---|---|---|---|---|---|---|
|
Part 2: ΔAUC0-12 Hours QTcF Values on Day 4 (LQT-1213 16 mg TID) Compared to the Time-matched on Day 1 (Placebo) Subgroup Analysis (≥ 500ms)
|
—
|
—
|
6413.29 msec*hour
Standard Deviation 175.189
|
6369.04 msec*hour
Standard Deviation 200.818
|
—
|
—
|
Adverse Events
Dofetilide
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Dofetilide + Low Dose LQT-1213 TID 0.25 mg/kg (Days 3 and 4)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Dofetilide + Mid Dose LQT-1213 TID 0.50 mg/kg (Days 5 and 6)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Dofetilide + High Dose LQT-1213 0.70 mg/kg on (Days 7 and 8)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Dofetilide + Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
LQT-1213 16 mg TID
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
LQT-1213 7 mg TID
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo Matching LQT-1213 16 mg TID
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo Matching LQT-1213 7 mg TID
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Dofetilide
n=30 participants at risk
Dofetilide 500 ug bid Day 1 and Day 2
|
Dofetilide + Low Dose LQT-1213 TID 0.25 mg/kg (Days 3 and 4)
n=29 participants at risk
Dofetilide + Low dose LQT-1213 TID 0.25 mg/kg (Days 3 and 4)
|
Dofetilide + Mid Dose LQT-1213 TID 0.50 mg/kg (Days 5 and 6)
n=29 participants at risk
Dofetilide + Mid dose LQT-1213 TID 0.50 mg/kg (Days 5 and 6)
|
Dofetilide + High Dose LQT-1213 0.70 mg/kg on (Days 7 and 8)
n=25 participants at risk
Dofetilide + High Dose LQT-1213 0.70 mg/kg on (Days 7 and 8)
|
Dofetilide + Placebo
n=29 participants at risk
Dofetilide + Placebo Day 3 to Day 8
|
LQT-1213 16 mg TID
n=6 participants at risk
LQT-1213 16 mg TID Day 2 to Day 4 (48 mg Daily)
|
LQT-1213 7 mg TID
n=6 participants at risk
LQT-1213 7 mg TID Day 2 to Day 4 (21 mg Daily)
|
Placebo Matching LQT-1213 16 mg TID
n=6 participants at risk
Placebo matching LQT-1213 16 mg TID (Day 1)
|
Placebo Matching LQT-1213 7 mg TID
n=6 participants at risk
Placebo matching LQT-1213 7 mg TID (Day 1)
|
|---|---|---|---|---|---|---|---|---|---|
|
General disorders
Vessel puncture site pain
|
0.00%
0/30 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
6.9%
2/29 • Number of events 2 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/25 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
13.8%
4/29 • Number of events 4 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/30 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/25 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
6.9%
2/29 • Number of events 2 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
|
Cardiac disorders
Palpitations
|
0.00%
0/30 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/25 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
6.9%
2/29 • Number of events 2 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/30 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/25 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
6.9%
2/29 • Number of events 2 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
16.7%
1/6 • Number of events 1 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/30 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/25 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
33.3%
2/6 • Number of events 2 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
16.7%
1/6 • Number of events 1 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
|
Skin and subcutaneous tissue disorders
Skin tightness
|
0.00%
0/30 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/25 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
16.7%
1/6 • Number of events 1 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
16.7%
1/6 • Number of events 1 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
|
Skin and subcutaneous tissue disorders
Skin warm
|
0.00%
0/30 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/25 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
16.7%
1/6 • Number of events 1 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/30 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/25 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
16.7%
1/6 • Number of events 1 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis atrophic
|
0.00%
0/30 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/25 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
16.7%
1/6 • Number of events 1 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
|
Skin and subcutaneous tissue disorders
Electrode site irritation
|
0.00%
0/30 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/25 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/29 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
16.7%
1/6 • Number of events 1 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
0.00%
0/6 • Part 1 : Period 1 (Day 1 to Day 10) and Period 2 (Day 1 to Day 17). Part 2: 12 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place