Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| American Heart Association | OTHER |
| Purdue University | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Torsades de pointes (TdP) is a potentially fatal ventricular arrhythmia associated with corrected QT (QTc) interval prolongation. More than 50 commonly used drugs available on the US market may cause QTc interval prolongation and TdP. While TdP occurs more commonly in women, 33-45% of all cases of TdP have occurred in men. Older age is a risk factor for drug-induced TdP in men, possibly due to declining serum testosterone concentrations. Available evidence shows an inverse relationship between QTc intervals and serum testosterone concentrations. In addition, experimental data, including those from the investigators' laboratory, suggest that both exogenous testosterone or progesterone administration may be protective against prolongation of ventricular repolarization and TdP. Specific Aim: Establish the influence of transdermal testosterone administration and oral progesterone administration as preventive methods by which to diminish the degree of drug-induced QT interval prolongation in men 65 years of age or older. Hypothesis: Transdermal testosterone administration and oral progesterone administration both effectively attenuate drug-induced QT interval response in older men. To test this hypothesis, transdermal testosterone, oral progesterone or placebo will be administered in a 3-way crossover study to men 65 years of age or older. QTc interval response to low-dose ibutilide will be assessed. The primary endpoints will be Fridericia-corrected QT interval (QTF) response to ibutilide, in the presence and absence of testosterone, and in the presence or absence of progesterone: 1) Effect on pre-ibutilide QTF, 2) Effect on maximum post-ibutilide QTF, 3) Effect on % change in post-ibutilide QTF, and 2) Area under the QTF interval-time curves.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Testosterone - progesterone - placebo | Experimental | Subjects received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days |
|
| Testosterone - placebo - progesterone | Experimental | Subjects received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo ( 2 capsules) once daily every morning x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. |
|
| Progesterone - testosterone - placebo | Experimental | Subjects received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo (2 capsules) once daily every morning x 7 days |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Testosterone | Drug | Subjects will receive transdermal testosterone gel 1% 100 mg daily for 7 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Baseline (Pre-ibutilide) Individualized Rate-corrected QT Interval (QTF) | QT interval is an electrocardiogram (ECG) measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers (EP Calipers 1.6). QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. Only clearly discernable QT intervals were measured. QT intervals vary with heart rate, and therefore must be corrected for heart rate. QT intervals were corrected using the Fridericia (QTF) method. The baseline QTF assesses the influence of testosterone and progesterone on naturally-occurring (before ibutilide administration) QTF | Following 7 days of testosterone, progesterone or placebo |
| Maximum QTF Following Ibutilide 0.003 mg/kg | QT interval is an ECG measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. QT intervals vary with heart rate, and therefore must be corrected for heart rate. QT intervals were corrected using the Fridericia (QTF) method. Maximum QTF is the longest QTF measured following ibutilide at any time point. | Within 8 hours following ibutilide administration |
| Maximum Percent Change From Pretreatment Value in QTF Following Ibutilide 0.003 mg/kg | QT interval is an ECG measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. QT intervals were corrected using the Fridericia (QTF) method. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the QTF Versus Time Curve for 0-1 Hour Following Ibutilide 0.003 mg/kg | Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. Area under the QTF curve was calculated using the trapezoidal rule and reflects overall QTF interval "exposure" over time. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| James E Tisdale, PharmD | Purdue University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31545681 | Background | Muensterman ET, Jaynes HA, Sowinski KM, Overholser BR, Shen C, Kovacs RJ, Tisdale JE. Effect of Transdermal Testosterone and Oral Progesterone on Drug-Induced QT Interval Lengthening in Older Men: A Randomized, Double-Blind, Placebo-Controlled Crossover-Design Study. Circulation. 2019 Sep 24;140(13):1127-1129. doi: 10.1161/CIRCULATIONAHA.119.041395. Epub 2019 Sep 23. No abstract available. | |
| 33020898 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
n=77 subjects initially assessed for eligibility; n=16 declined to participate, n= 49 excluded (met one or more exclusion criteria); n=22 provided written informed consent (these participants were not considered to be enrolled); n= 8 excluded after providing consent because they were found to meet an exclusion criterion
Recruitment began in July 2015; procedures were completed on last enrolled subject in October 2017.
Subjects were recruited from advertisements placed in a seniors magazine, assisted living facilities, and local health fairs.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Testosterone - Progesterone - Placebo | Subjects received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
| FG001 | Testosterone - Placebo - Progesterone | Subjects received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo ( 2 capsules) once daily every morning x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
| FG002 | Progesterone - Testosterone - Placebo | Subjects received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo (2 capsules) once daily every morning x 7 days Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
| FG003 | Progesterone - Placebo - Testosterone | Subjects received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo (2 capsules) once daily every morning x 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
| FG004 | Placebo - Testosterone - Progesterone | Subjects received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
| FG005 | Placebo - Progesterone - Testosterone | Subjects received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Men 65 years of age or older were enrolled
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Men 65 years of age or older were enrolled. Exclusion criteria were: prostate cancer; history of prostate or breast cancer; benign prostatic hyperplasia; weight < 60 kg or > 135 kg; serum potassium < 3.6 mEq/L; serum magnesium < 1.8 mg/dL; hematocrit < 26%; hepatic transaminases > 3x upper limit of normal; baseline Bazett's-corrected QTc interval > 450 ms; heart failure with reduced ejection fraction (left ventricular ejection fraction < 40%); family or personal history of long QT syndrome, arrhythmias or sudden cardiac death; permanently paced ventricular rhythm; concomitant use of any QT interval-prolonging drug or strong non-QT interval-prolonging cytochrome P450 3A inhibitors. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Baseline (Pre-ibutilide) Individualized Rate-corrected QT Interval (QTF) | QT interval is an electrocardiogram (ECG) measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers (EP Calipers 1.6). QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. Only clearly discernable QT intervals were measured. QT intervals vary with heart rate, and therefore must be corrected for heart rate. QT intervals were corrected using the Fridericia (QTF) method. The baseline QTF assesses the influence of testosterone and progesterone on naturally-occurring (before ibutilide administration) QTF | Posted | Mean | Standard Deviation | ms | Following 7 days of testosterone, progesterone or placebo |
|
8 days per study phase
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Testosterone | Testosterone gel 1% 100 mg daily x 7 days Oral placebo capsules once daily for 7 days Testosterone: Subjects will receive transdermal testosterone gel 1% 100 mg daily for 7 days Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. James E Tisdale | Indiana University | 317-880-5418 | jtisdale@iu.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 10, 2017 | Mar 28, 2019 | Prot_SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D008133 | Long QT Syndrome |
| D016171 | Torsades de Pointes |
| D040242 | Risk Reduction Behavior |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D000075224 | Cardiac Conduction System Disease |
Not provided
Not provided
| ID | Term |
|---|---|
| D013739 | Testosterone |
| D011374 | Progesterone |
| D016568 | Drugs, Generic |
| D007785 | Lactose |
| C067192 | ibutilide |
| ID | Term |
|---|---|
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Progesterone - placebo - testosterone | Experimental | Subjects received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal placebo gel once daily every morning for 7 days and oral placebo (2 capsules) once daily every morning x 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. |
|
| Placebo - testosterone - progesterone | Experimental | Subjects received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. |
|
| Placebo - progesterone - testosterone | Experimental | Subjects received transdermal placebo gel once daily every morning for 7 days and oral placebo once daily every morning x 7 days. After a washout period of at least 13 days, they then received oral progesterone 400 mg (2 x 200 mg capsules) once every evening for 7 days and transdermal placebo gel once daily every morning for 7 days. After a washout period of at least 13 days, they then received transdermal testosterone gel 1% 100 mg once daily in the morning and two (2) oral placebo capsules x 7 days. |
|
|
| Progesterone | Drug | Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days |
|
|
| Placebo | Drug | Subjects will receive placebo transdermal gel and placebo (lactose) capsules |
|
|
| Ibutilide | Drug | Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
|
|
| Within 8 hours of ibutilide administration |
| 1 hour following ibutilide administration |
| Number of Participants With Adverse Effects Associated With Testosterone, Progesterone and Placebo | Adverse effects were assessed by study investigators using telephone calls during the 7-day treatment period in each phase, as well as by asking participants about adverse effects on ibutilide administration days | During 7 day administration periods |
| Derived |
| Tomaselli Muensterman E, Jaynes HA, Sowinski KM, Overholser BR, Shen C, Kovacs RJ, Tisdale JE. Transdermal Testosterone Attenuates Drug-Induced Lengthening of Both Early and Late Ventricular Repolarization in Older Men. Clin Pharmacol Ther. 2021 Jun;109(6):1499-1504. doi: 10.1002/cpt.2072. Epub 2020 Nov 15. |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Age, Continuous | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| OG000 |
| Testosterone |
Testosterone gel 1% 100 mg daily x 7 days Testosterone: Subjects will receive transdermal testosterone gel 1% 100 mg daily for 7 days Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
| OG001 | Progesterone | Progesterone 400 mg orally daily x 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
| OG002 | Placebo | Dual matching placebo capsules and placebo topical gel every day x 7 days Placebo Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval |
|
|
|
| Primary | Maximum QTF Following Ibutilide 0.003 mg/kg | QT interval is an ECG measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. QT intervals vary with heart rate, and therefore must be corrected for heart rate. QT intervals were corrected using the Fridericia (QTF) method. Maximum QTF is the longest QTF measured following ibutilide at any time point. | Posted | Mean | Standard Deviation | ms | Within 8 hours following ibutilide administration |
|
|
|
|
| Primary | Maximum Percent Change From Pretreatment Value in QTF Following Ibutilide 0.003 mg/kg | QT interval is an ECG measure of ventricular repolarization. Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. QT intervals were corrected using the Fridericia (QTF) method. | Posted | Mean | Standard Deviation | Percent change | Within 8 hours of ibutilide administration |
|
|
|
|
| Secondary | Area Under the QTF Versus Time Curve for 0-1 Hour Following Ibutilide 0.003 mg/kg | Prolonged QT interval is a marker of increased risk of the ventricular arrhythmia known as torsades de pointes, which can cause sudden cardiac death. Three 12-lead ECGs were obtained ~ 1 minute apart immediately at the end of the ibutilide infusion and at 5, 10, 15, 20, 30, and 45 minutes and 1, 2, 4, 6, and 8 hours post-infusion. QT intervals were measured from ECG lead II by one investigator (E.T.M.) who was blinded to the subjects' assigned treatment phases. QT intervals were measured using computerized high-resolution electronic calipers. QT and RR intervals at each time point were averaged over 3 consecutive complexes. The end of the T-wave was determined via the tangent method. Area under the QTF curve was calculated using the trapezoidal rule and reflects overall QTF interval "exposure" over time. | Posted | Mean | Standard Deviation | ms·hr | 1 hour following ibutilide administration |
|
|
|
|
| Secondary | Number of Participants With Adverse Effects Associated With Testosterone, Progesterone and Placebo | Adverse effects were assessed by study investigators using telephone calls during the 7-day treatment period in each phase, as well as by asking participants about adverse effects on ibutilide administration days | Posted | Count of Participants | Participants | During 7 day administration periods |
|
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 0 |
| 14 |
| EG001 | Progesterone | Progesterone 400 mg orally daily x 7 days Transdermal placebo gel once daily for 7 days Progesterone: Subjects will receive oral progesterone 400 mg (two x 200 mg capsules) once daily every evening for 7 days Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval | 0 | 14 | 0 | 14 | 1 | 14 |
| EG002 | Placebo | Dual matching placebo capsules and placebo topical gel every day x 7 days Placebo Ibutilide: Ibutilide 0.003 mg/kg administered to all subjects in all phases to moderately lengthen the QT interval | 0 | 14 | 0 | 14 | 1 | 14 |
| Rash on gel application site | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
Not provided
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017180 | Tachycardia, Ventricular |
| D013610 | Tachycardia |
| D001519 | Behavior |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D003339 | Corpus Luteum Hormones |
| D045167 | Progesterone Congeners |
| D004364 | Pharmaceutical Preparations |
| D004187 | Disaccharides |
| D009844 | Oligosaccharides |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D000073893 | Sugars |
| Title | Measurements |
|---|---|
|
| >0.99 |
| Superiority |