A Study of LY2623091 in Participants With High Blood Pressure

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as LY2623091 in participants with high blood pressure.

Official Title
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A Randomized, Placebo-Controlled, Double-Blinded, Parallel, Phase 2a Study to Evaluate the Safety and Efficacy of LY2623091 in Patients With Primary Hypertension

Conditions
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Primary Hypertension

Intervention / Treatment
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* Drug: LY2623091
* Drug: Tadalafil
* Drug: Spironolactone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a history of hypertension. If participants are naïve to treatment of hypertension, or have not been treated with any antihypertensive medications within the 30 days immediately prior to screening: Have seated systolic (SBP) of ≥140 and <170 millimeters of mercury (mmHg) at screening and at the end of the lead-in period. If participants are currently being treated for hypertension: Are taking a stable dose of 1 or 2 antihypertensive medications for at least the previous 30 days. A combination antihypertensive medication from 2 classes is considered as 2 antihypertensive medications. Are willing to discontinue the antihypertensive medications during the study. Have seated SBP of ≥140 and <170 mmHg at the end of the lead-in period. Have a body mass index (BMI) ≥18.5 and <40 kilograms/m^2. Exclusion Criteria: Have a history of severe hypertension (defined as SBP ≥180 mmHg and/or diastolic (DBP) ≥120 mmHg), secondary hypertension, symptomatic postural hypotension, or hospitalization due to hypertension. Have SBP ≥180 mmHg and/or DBP ≥110 mmHg at screening, lead-in period, or randomization. Have a history of hospitalization due to hyperkalemia, or history of drug discontinuation due to elevated serum potassium levels. Have a serum potassium ≤3.5 or >5.0 millimoles per liter (mmol/L). Have an estimated glomerular filtration rate (eGFR) <50 milliliters/minute/1.73 m^2.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 6 milligrams (mg) LY2623091<br>6 mg LY2623091 with placebo for blinding administered orally once daily for 4 weeks. | Drug: LY2623091<br>* Administered orally<br>* Other names: Mineralocorticoid Receptor Antagonist;Drug: Placebo<br>* Administered orally<br>|
| Experimental: 13 mg LY2623091<br>13 mg LY2623091 with placebo for blinding administered orally once daily for 4 weeks. | Drug: LY2623091<br>* Administered orally<br>* Other names: Mineralocorticoid Receptor Antagonist;Drug: Placebo<br>* Administered orally<br>|
| Experimental: 24.5 mg LY2623091<br>24.5 mg LY2623091 with placebo for blinding administered orally once daily for 4 weeks. | Drug: LY2623091<br>* Administered orally<br>* Other names: Mineralocorticoid Receptor Antagonist;Drug: Placebo<br>* Administered orally<br>|
| Experimental: 13 mg LY2623091 + 20 mg tadalafil<br>13 mg LY2623091 and 20 mg of tadalafil with placebo for blinding administered orally once daily for 4 weeks. | Drug: LY2623091<br>* Administered orally<br>* Other names: Mineralocorticoid Receptor Antagonist;Drug: Tadalafil<br>* Administered orally<br>* Other names: LY450190;Drug: Placebo<br>* Administered orally<br>|
| Experimental: 20 mg tadalafil<br>20 mg tadalafil with placebo for blinding administered orally once daily for 4 weeks. | Drug: Tadalafil<br>* Administered orally<br>* Other names: LY450190;Drug: Placebo<br>* Administered orally<br>|
| Active Comparator: Spironolactone<br>25 mg titrated to 50 mg as tolerated of spironolactone (open label) administered orally once daily for 4 weeks. | Drug: Spironolactone<br>* Administered orally<br>|
| Placebo Comparator: Placebo<br>Placebo for blinding administered orally once daily for 4 weeks. | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 4 Weeks in Seated Systolic Blood Pressure (SBP) | Change from baseline in SBP as measured by a cuff. Least squares (LS) mean change from baseline was calculated using a mixed model repeating measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. | Baseline, 4 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 4 Weeks in Seated Diastolic Blood Pressure (DBP) | Change from baseline in DBP as measured by a cuff. LS mean change from baseline was calculated using a MMRM with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. | Baseline, 4 Weeks | 
| Change From Baseline to 4 Weeks in 24 Hour Ambulatory Blood Pressure Monitoring (ABPM) | The LS mean change in blood pressure is calculated after adjusting for baseline, treatment and race using an analysis of covariance (ANCOVA). | Baseline, 4 Weeks | 
| Change From Baseline to 4 Weeks in Serum Potassium | Potassium measurement as measured by standard laboratory tests. The LS mean change in potassium is calculated using MMRM with adjustment for baseline, treatment, visit, treatment*visit and race. | Baseline, 4 Weeks | 
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2623091 |  | 2 hours post-dose at 4 Weeks |