Clinical trial

Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening: Reducing the Risk of Drug-Induced QT Interval Lengthening in Women

Name

1806935117

Description

This research will determine if oral progesterone attenuates drug-induced QT interval lengthening in a) Postmenopausal women 50 years of age or older, and b) Premenopausal women studied during the ovulation phase of the menstrual cycle. This investigation will consist of two concurrent prospective, randomized, double-blind, placebo-controlled crossover-design studies in a) Postmenopausal women, and b) Premenopausal women. Each subject will take progesterone or placebo capsules for 1 week. After a two-week "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

Trial arms

Trial start

2019-03-26

Estimated PCD

2024-05-21

Trial end

2024-05-23

Status

Completed

Phase

Early phase I

Treatment

Progesterone

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

Arms:

Postmenopausal women: Progesterone, Premenopausal women: Progesterone

Ibutilide

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

Arms:

Postmenopausal women: Placebo, Postmenopausal women: Progesterone, Premenopausal women: Placebo, Premenopausal women: Progesterone

Other names:

Corvert

Size

Primary endpoint

Baseline (pre-ibutilide) QT-F and QT-Fram intervals

After 7 days of treatment with oral progesterone or placebo, prior to receiving ibutilide

Maximum post-ibutilide QT-F and QT-Fram intervals

Prior to ibutilide; at 5 minutes into the 10-minute ibutilide infusion; end of infusion; and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours after the ibutilide infusion

% change from baseline (pre-ibutilide) in maximum QT-F and QT-Fram intervals

Prior to ibutilide; at 5 minutes into the 10-minute ibutilide infusion; end of infusion; and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours after the ibutilide infusion

Area under the QT-F and QT-Fram versus time curves during and for 1 hour following ibutilide infusion

Prior to ibutilide; at 5 minutes into the 10-minute ibutilide infusion; end of infusion; and at 5, 10, 15, 20, 30, and 45 minutes and 1 hour after the ibutilide infusion

Area under the QT-F and QT-Fram versus time curves during and for 8 hours following ibutilide infusion

Prior to ibutilide; at 5 minutes into the 10-minute ibutilide infusion; end of infusion; and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours after the ibutilide infusion

Eligibility criteria

Inclusion Criteria: Postmenopausal women: * 50 years of age or older * No menstrual periods for 365 days or longer Premenopausal women: - 21-40 years of age Exclusion Criteria: * History of breast, uterine or ovarian cancer * History of hysterectomy and/or ovariectomy * Weight \> 135 kg * Serum K+ \< 3.6 mEq/L; * Serum Mg2+ \< 1.8 mg/dL; * Hematocrit \< 26%; * Hepatic transaminases \> 3x upper limit of normal; * Baseline Bazett's-corrected QT interval \> 450 ms * Taking hormone replacement therapy * Diagnosis of heart failure * Symptoms associated with heart failure: * Pitting edema \> 2+ * Crackles or rales on lung auscultation * S3 or S4 heart sounds * Unable to climb at least 2 flights of stairs without becoming short of breath * Current ECG rhythm of atrial fibrillation or other tachyarrhythmia * Family or personal history of long-QT syndrome or sudden cardiac death not associated with acute myocardial infarction * Concomitant use of any QTc interval-prolonging drug. * Permanently paced ventricular rhythm * Pregnancy * Using any hormonal contraceptives \[oral contraceptives, hormone-secreting intrauterine devices (IUDs), hormonal implants\]

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 16, 'type': 'ACTUAL'}}

Updated at

2024-05-31

1 organization

2 products

3 indications

Organization

Product

Indication

Indication

Indication

Product