Reducing the Risk of Drug-Induced QT Interval Lengthening in Women

NCT03834883 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 1806935117
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Long QT Syndrome; Abnormalities, Drug-Induced

Outcome Measures

Primary Outcomes (4)

• Baseline (Pre-ibutilide) QT-F Intervals

  QT intervals will be corrected for heart rate using the Fridericia method

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

• Maximum Post-ibutilide QT-F Intervals

  Maximum post-ibutilide QT-F 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 Intervals

  % change from baseline (pre-ibutilide) in maximum QT-F 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 Versus Time Curves During and for 1 Hour Following Ibutilide Infusion

  Area under the QT-F versus time curves during and for 1 hour

  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

Secondary Outcomes (8)

• Baseline (Pre-ibutilide) Heart Rate-corrected J-Tpeak (J-Tpeakc) Intervals

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

• Maximum Post-ibutilide J-Tpeakc 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 J-Tpeakc 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 J-Tpeakc Versus Time Curve 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

• Baseline (Pre-ibutilide) Tpeak-Tend Intervals

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

Study Arms (4)

Postmenopausal women: Progesterone

EXPERIMENTAL

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

Drug: Progesterone; Drug: Ibutilide

Postmenopausal women: Placebo

PLACEBO COMPARATOR

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Drug: Ibutilide

Premenopausal women: Progesterone

EXPERIMENTAL

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

Drug: Progesterone; Drug: Ibutilide

Premenopausal women: Placebo

PLACEBO COMPARATOR

Subjects will receive oral placebo, two capsules once daily every evening for 7 days

Drug: Ibutilide

Interventions

Progesterone DRUG

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

Postmenopausal women: Progesterone; Premenopausal women: Progesterone

Ibutilide DRUG

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

Also known as: Corvert

Postmenopausal women: Placebo; Postmenopausal women: Progesterone; Premenopausal women: Placebo; Premenopausal women: Progesterone

Eligibility Criteria

• Age: 21 Years+
• Gender Eligibility Details: Postmenopausal - 50 years of age or older and no menstrual period for 365 days or longer Premenopausal - 21-40 years of age
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women:
• years of age or older
• No menstrual periods for 365 days or longer
• Premenopausal women:
• \- 21-40 years of age

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana University: lead
• American Heart Association: collaborator
• Purdue University: collaborator

Study Sites (1)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Long QT Syndrome; Abnormalities, Drug-Induced

Interventions

Progesterone; ibutilide

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Results Point of Contact

• Title: James E. Tisdale, PharmD
• Organization: Purdue University

jtisdale@purdue.edu

317-880-5418

Study Officials

• James E Tisdale, PharmD

  Purdue University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, College of Pharmacy, Purdue University

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 8, 2019
• Study Start: March 26, 2019
• Primary Completion: May 21, 2024
• Study Completion: May 23, 2024
• Last Updated: July 1, 2025
• Results First Posted: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)