NCT03070470

CiPA Phase 1 ECG Biomarker Validation Study

Comprehensive in Vitro Proarrhythmia Assay (CiPA) Clinical Phase 1 ECG Biomarker Validation Study (CiPA Phase 1 ECG Biomarker Study)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: Food and Drug Administration (FDA) · Federal
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This study will assess whether exposure response analysis of the electrocardiographic QTc and J-Tpeakc intervals in Phase 1 clinical pharmacology studies can be used to confirm that drugs that predominantly block the potassium channel encoded by the human ether-à-go-go-related gene (hERG) with approximately equipotent late sodium and/or calcium block ("balanced ion channel" drugs) do not cause J-Tpeakc prolongation and that drugs that predominantly block hERG without late sodium or L-type calcium current block ("predominant hERG" drugs) cause QTc prolongation.

Detailed description

This study will assess whether exposure response analysis of the electrocardiographic QTc and J-Tpeakc intervals in Phase 1 clinical pharmacology studies can be used to confirm that "balanced ion channel" drugs do not cause J-Tpeakc prolongation and that "predominant hERG" drugs cause QTc prolongation. This clinical study consists of 2 parts: a 50-subject parallel part (Part 1) and a 10-subject crossover part (Part 2). Up to 74 healthy subjects will be enrolled (including 14 potential replacement subjects). Part 1 will be a double-blind, randomized, placebo-controlled, 1 period parallel design to assess the effect of 4 marketed drugs and 1 placebo on the QTc and J-Tpeakc intervals in 50 healthy subjects. A parallel design similar to a single or multiple ascending dose (SAD/MAD) Phase 1 study will be used that will result in each study drug being administered to 10 subjects, and placebo to 10 subjects, in 1 period of 3 consecutive days to achieve low and high drug exposure. Part 2 will be a double-blind, randomized, 2-period crossover design to assess the effect of hERG block (dofetilide) versus calcium block (diltiazem) on the QTc and J-Tpeakc intervals in 10 healthy subjects on Days 1, 2, and 3 (Period 1) and Days 8, 9, and 10 (Period 2).

Conditions

• Drug-induced QT Prolongation
• Pharmacokinetics
• Pharmacodynamics

Interventions

Type	Name	Description
DRUG	Ranolazine	Ranolazine 1500 mg orally two times per day for 2.5 days
DRUG	Verapamil	Verapamil 120 mg immediate release (IR) morning and afternoon doses on Days 1 and 2, 240 mg extended release (ER) evening dose on Days 1 and 2, and 120 mg IR morning dose on Day 3 (all oral doses)
DRUG	Lopinavir / Ritonavir	Lopinavir / Ritonavir 800 mg / 200 mg orally two times per day for 2.5 days
DRUG	Chloroquine	Chloroquine 1000 mg on Day 1, 500 mg on Day 2, 1000 mg on Day 3 (all oral doses)
DRUG	Placebo	Placebo (administered orally)
DRUG	Dofetilide and Diltiazem	In one period subjects receive Dofetilide 0.125 mg on Day 1, 0.375 mg on Day 3. In a second period (randomized cross-over) subject receive Diltiazem 120 mg IR morning dose on Day 8, 240 mg ER evening dose on Days 8 and 9, and 120 mg IR on Day 10 with coadministration of 0.25 mg dofetilide on Day 10.

Timeline

• Start date: 2017-03-14
• Primary completion: 2017-06-26
• Completion: 2017-06-26
• First posted: 2017-03-03
• Last updated: 2020-01-18
• Results posted: 2020-01-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study