A Study of LY3322207 in Healthy Participants and in Participants With Hypertension (High Blood Pressure)

• ClinicalTrials.gov Identifier: NCT03590860
• Recruitment Status: Terminated
• First Posted: July 18, 2018
• Last Update Posted: February 25, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The purpose of this study is to investigate the safety of the study drug known as LY3322207. Participants must be healthy or must have hypertension (high blood pressure). Participants with hypertension may already be taking a common drug to reduce blood pressure called an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB).

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: LY3322207; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Part C will be open label
• Primary Purpose: Basic Science
• Official Title: A Safety, Tolerability, and Pharmacokinetic Study of Single and Multiple Ascending Doses of LY3322207 in Healthy Subjects and Subjects With Hypertension on ACE I/ARB Therapy
• Actual Study Start Date: July 13, 2018
• Actual Primary Completion Date: January 17, 2019
• Actual Study Completion Date: January 17, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: LY3322207 (Part A); LY3322207 administered subcutaneously (SC)	Drug: LY3322207; Administered by SC injection
Placebo Comparator: Placebo (Part A); Placebo matching LY3322207 administered SC	Drug: Placebo; Administered by SC injection
Experimental: LY3322207 (Part B); LY3322207 administered SC once weekly	Drug: LY3322207; Administered by SC injection
Placebo Comparator: Placebo (Part B); Placebo matching LY3322207 administered SC once weekly	Drug: Placebo; Administered by SC injection
Experimental: LY3322207 (Part C); LY3322207 administered SC in participants with hypertension	Drug: LY3322207; Administered by SC injection

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with One or More Serious Adverse Events (Part A) [ Time Frame: Baseline up to approximately 31 days ]
   Serious and other non-serious adverse events will be reported in the Adverse Events Module
2. Number of Participants with One or More Serious Adverse Events (Part B) [ Time Frame: Baseline up to approximately 9 weeks ]
   Serious and other non-serious adverse events will be reported in the Adverse Events Module
3. Number of Participants with One or More Serious Adverse Events (Part C) [ Time Frame: Baseline up to approximately 9 weeks ]
   Serious and other non-serious adverse events will be reported in the Adverse Events Module

Secondary Outcome Measures :

1. Area Under the Concentration Versus Time Curve (AUC) of LY3322207 (Part A) [ Time Frame: Predose up approximately 31 days ]
   Pharmacokinetics (PK): AUC of LY3322207
2. Area Under the Concentration Versus Time Curve (AUC) of LY3322207 (Part B) [ Time Frame: Predose up to approximately 9 weeks ]
   PK: AUC of LY3322207
3. Area Under the Concentration Versus Time Curve (AUC) of LY3322207 (Part C) [ Time Frame: Predose up to approximately 9 weeks ]
   PK: AUC of LY3322207
4. Maximum Concentration (Cmax) of LY3322207 (Part A) [ Time Frame: Predose up approximately 31 days ]
   PK: Cmax of LY3322207
5. Maximum Concentration (Cmax) of LY3322207 (Part B) [ Time Frame: Predose up to approximately 9 weeks ]
   PK: Cmax of LY3322207
6. Maximum Concentration (Cmax) of LY3322207 (Part C) [ Time Frame: Predose up to approximately 9 weeks ]
   PK: Cmax of LY3322207
7. Time to reach Cmax (Tmax) of LY3322207 (Part A) [ Time Frame: Predose up to approximately Day 31 ]
   PK: Tmax of LY3322207
8. Time to reach Cmax (Tmax) of LY3322207 (Part B) [ Time Frame: Predose up to approximately 9 weeks ]
   PK: Tmax of LY3322207
9. Time to reach Cmax (Tmax) of LY3322207 (Part C) [ Time Frame: Predose up to approximately 9 weeks ]
   PK: Tmax of LY3322207
10. Change from Baseline in Systolic Blood Pressure (SBP) (Part A) [ Time Frame: Baseline up approximately 31 days ]
    Supine position
11. Change from Baseline in Systolic Blood Pressure (SBP) (Part B) [ Time Frame: Baseline up to approximately 9 weeks ]
    Supine position
12. Change from Baseline in Systolic Blood Pressure (SBP) (Part C) [ Time Frame: Baseline up to approximately 9 weeks ]
    Supine position
13. Change from Baseline in Diastolic Blood Pressure (DBP) (Part A) [ Time Frame: Baseline up approximately 31 days ]
    Supine position
14. Change from Baseline in Diastolic Blood Pressure (DBP) (Part B) [ Time Frame: Baseline up to approximately 9 weeks ]
    Supine position
15. Change from Baseline in Diastolic Blood Pressure (DBP) (Part C) [ Time Frame: Baseline up to approximately 9 weeks ]
    Supine position
16. Change from Baseline in Heart Rate (Part A) [ Time Frame: Baseline up approximately 31 days ]
    Supine position
17. Change from Baseline in Heart Rate (Part B) [ Time Frame: Baseline up to approximately 9 weeks ]
    Supine position
18. Change from Baseline in Heart Rate (Part C) [ Time Frame: Baseline up to approximately 9 weeks ]
    Supine position

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy males, as determined by medical history and physical examination, must agree to use a medically appropriate method of birth control and agree not to donate sperm from start of dosing until 90 days beyond last dose

• Healthy females, as determined by medical history and physical examination, of non-child bearing potential due to:

  • Menopause: spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as anorexia nervosa and not taking medications that induced the amenorrhea (for example: oral contraceptives, hormones, gonadotropin releasing hormone, anti-estrogens, selective estrogen receptor modulators, or chemotherapy)
  • Surgical sterilization
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow site specific study procedures
• Have a Body Mass Index (BMI) 18 to 30 kilogram per square meter (kg/m²) at entry
• Have clinical laboratory test results within normal reference range for the population or site, or results with acceptable deviations that are judged not clinically significant
• Be 18 to 55 years old for either Part A or Part B of the study, or 18 to 65 years old for Part C only
• For Part C: must have been treated with a stable dose of ACE-I or ARB for at least 1 month

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 60 days from, a clinical trial involving an investigational drug that has not received regulatory approval
• Have previously completed or withdrawn from this study or any other study investigating this study drug
• Have a history or presence of medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease, significant atopy, or any clinically significant laboratory abnormality that would preclude study participation
• Have abnormality in the 12-lead electrocardiogram (ECG) which increases study risk
• Have confirmed QT interval corrected by Bazett's method (QTcB) or Fridericia's (QTcF) method >450 millisecond (msec) for men and >470 msec for women
• Have prior Q-wave myocardial infarction or other, specific heart abnormalities, arrhythmias or fibrillations
• Have an abnormal blood pressure (supine) defined as diastolic blood pressure greater than (>)95 or less than (<)50 millimeters of mercury (mmHg) and/or systolic blood pressure >160 or <90 mmHg
• Show evidence of human immunodeficiency virus (HIV), hepatitis C, or hepatitis B
• Have donated blood of more than 100 mL (milliliters) within the last month
• Are unwilling to stop alcohol consumption while resident in the Clinical Research Unit
• Have an average weekly alcohol intake that exceeds 21 units per week (1 unit equal to (=) 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
• Have an abnormal blood pressure (supine) defined as diastolic blood pressure >95 or <50 mmHg and/or systolic blood pressure >160 or <90 mmHg
• Have serum potassium outside normal range
• Have had lymphoma, leukemia, or any malignancy within the past 5 years
• Have clinically significant multiple or severe drug allergies or intolerance
• Are lactating women
• Positive findings for known drugs of abuse
• Have received treatment with biologic agents within 3 months or 5 half-lives prior to dosing
• Participation in any other clinical trial involving a study drug or off-label use of a drug or device, or any other type of medical research judged not to be compatible with this study
• Have estimated glomerular filtration rate (eGFR) < 60 milliliters per minute per 1.73 square meter (mL/min/1.73 m²) for Parts A and B of this study, or eGFR < 50 mL/min/1.73 m² in Part C only
• For Part C: have a history of severe hypertension (defined as SBP greater than or equal to (≥)180 mmHg and/or DBP ≥120 mmHg), secondary hypertension, symptomatic postural hypotension, or hospitalization due to hypertension
• For Part C: have a history of supraventricular tachycardia (for example, atrial fibrillation), ventricular tachycardia, or other cardiac arrhythmia
• For Part C: have resting tachycardia (heart rate ≥100 beats per minute)
• For Part C: have New York Heart Association (NYHA) Class II, III, or IV heart failure, or had any of the following in the previous 3 months: coronary angioplasty, coronary stent placement, coronary bypass surgery or any significant cardiac surgery, myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack
• For Part C: have an automatic internal cardioverter-defibrillator
• For Part C: have diabetes

Contacts and Locations

Locations

Netherlands

PRA Health Sciences

Groningen, Netherlands, 9728 NZ

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03590860
• Other Study ID Numbers: 16771; I9K-MC-UCAA ( Other Identifier: Eli Lilly and Company ); 2018-002337-38 ( EudraCT Number )
• First Posted: July 18, 2018
• Last Update Posted: February 25, 2019
• Last Verified: February 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases