A Study of LY2623091 in Participants With High Blood Pressure

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Tadalafil; Drug: LY2623091; Drug: Spironolactone

• Study Type: Interventional
• Enrollment (Actual): 304
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Brampton, Canada, L6T 0G1
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Kelowna, Canada, V1Y3G8
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Peterborough, Canada, K9J 0B2
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Pointe Claire, Canada, H9R 4S3
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Quebec City, Canada, G1N 4V3
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Red Deer, Canada, T4N 6V7
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Sherbrooke, Canada, J1J 2G2
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Toronto, Canada, M9W 4L6
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Puerto Rico
  • Ponce, Puerto Rico, 00717-1322
    • Research and Cardiovascular Corp.
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico, Inc.
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Clinical Research Advantage
  • California
    • Concord, California, United States, 94520
      • John Muir Health Network - The Osteoporosis Center
    • Encinitas, California, United States, 92024
      • Encompass Clinical Research
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research LLC
    • Fort Lauderdale, Florida, United States, 33308
      • Alan Graff, MD, PA
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Sarasota, Florida, United States, 34239
      • Cardiovascular Center of Sarasota
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Medical Institute
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Diabetes and Osteoporosis Center
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Heart Clinical Research, LLC
    • Chicago, Illinois, United States, 60607
      • Cedar-Crosse Research Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
    • Muncie, Indiana, United States, 47304
      • Community Clinical Research Center
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
      • Grace Research
  • Maine
    • Auburn, Maine, United States, 04210
      • Maine Research Associates
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • AB Clinical Trials
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Metrolina Internal Medicine, P.A.
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Lillestol Research LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group, Ltd
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research Inc
    • Columbus, Ohio, United States, 43213
      • Columbus Clinical Research
    • Dayton, Ohio, United States, 45406
      • Dayton Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Foundation for Cardiovascular Research
    • Oklahoma City, Oklahoma, United States, 4052728481
      • COR Clinical Research LLC
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Mountain View Clinical Research, Inc
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc
    • Austin, Texas, United States, 78731-4309
      • Texas Diabetes and Endocrinology
    • Round Rock, Texas, United States, 78681
      • Texas Diabetes and Endocrinology, P.A.
  • Washington
    • Bellevue, Washington, United States, 98007-4209
      • Northwest Clinical Research Center
    • Tacoma, Washington, United States, 98405
      • Universal Research Group, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: July 17, 2014
• First Submitted That Met QC Criteria: July 17, 2014
• First Posted (Estimate): July 18, 2014

Study Record Updates

• Last Update Posted (Actual): June 26, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Phosphodiesterase Inhibitors; Diuretics, Potassium Sparing; Phosphodiesterase 5 Inhibitors; Spironolactone; Tadalafil; Mineralocorticoid Receptor Antagonists; Mineralocorticoids
• Other Study ID Numbers: 15525; I7T-MC-RMAH (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR