Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening

Summary

This research will determine if: 1) Oral progesterone attenuates drug-induced QT interval, J-Tpeak and Tpeak-Tend lengthening in postmenopausal women 50 years of age or older, and 2) Transdermal testosterone attenuates drug-induced QT interval, J-Tpeak and Tpeak-Tend lengthening in men 65 years of age or older. This investigation will consist of two concurrent prospective, randomized, double-blind, placebo-controlled crossover-design studies in a) Postmenopausal women, and b) Men 65 years of age or older. Study 1: Each postmenopausal woman will take progesterone or placebo capsules for 1 week. After a 14-day "washout" (no progesterone or placebo) each subject will then take the alternative therapy (progesterone or placebo) for 1 week. After 7 days of each treatment, subjects will present to the clinical research center to receive a small dose of the QT interval-lengthening drug ibutilide, and the effect on the QT, J-Tpeak and Tpeak-Tend intervals during the progesterone and placebo phases will be compared. Study 2: Each man 65 years of age or older will apply transdermal testosterone or transdermal placebo gel for 3 days. After a 7-day "washout" (no testosterone or placebo) each subject will then apply the alternative therapy (testosterone or placebo gel) for 1 week. After 3 days of each treatment, subjects will present to the clinical research center to receive a small dose of the QT interval-lengthening drug ibutilide, and the effect on the QT, J-Tpeak and Tpeak-Tend intervals during the testosterone and placebo phases will be compared.

Conditions

• Long QT Syndrome
• Abnormalities, Drug-Induced

Interventions

DRUG

Progesterone

Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days

DRUG

Ibutilide

Ibutilide 0.003 mg/kg administered to all subjects to modestly lengthen the QT interval

DRUG

Testosterone

Subjects will apply transdermal testosterone gel once daily every morning for 3 days

DRUG

Placebo

Lactose capsules

Sponsors & Collaborators

• Purdue University

  collaborator OTHER

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Harvard University

  collaborator OTHER

• Cedars-Sinai Medical Center

  collaborator OTHER

• Indiana University

  lead OTHER

Principal Investigators

• James E Tisdale, PharmD · Purdue University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

50 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-09-02

Primary Completion

2025-04-16

Completion

2025-04-16

FDA Drug

Yes

Countries

• United States

Study Locations