CiPA Phase 1 ECG Biomarker Validation Study

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.

Conditions

• Drug-induced QT Prolongation
• Pharmacokinetics
• Pharmacodynamics

Interventions

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.

Sponsors & Collaborators

• Spaulding Clinical Research LLC

  collaborator OTHER

• Food and Drug Administration (FDA)

  lead FED

Principal Investigators

• Carlos Sanabria, MD · Spaulding Clinical Research LLC

Study Design

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-03-14

Primary Completion

2017-06-26

Completion

2017-06-26

FDA Drug

Yes

Countries

• United States

Study Locations