Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this study is twofold: 1. To evaluate the effect of LY2189265 on how the body absorbs a blood pressure lowering drug (lisinopril) in participants with high blood pressure who are currently taking lisinopril. 2. To evaluate the effect of LY2189265 on heart rate and blood pressure in healthy volunteers when taken with a Beta-blocker drug (metoprolol). In Part 1, participants will receive four weekly injections of LY2189265 with continued use of normal lisinopril therapy. Part 2 is a cross-over study design. Participants will receive a single injection of LY2189265 in one period, and seven daily doses of metoprolol and a single injection of LY2189265 in another period.
Interventions
BIOLOGICALLY2189265
Administered subcutaneously
DRUGMetoprolol
Administered orally
DRUGLisinopril
Administered orally
DRUGPlacebo
Administered subcutaneously
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male participants: agree to use a reliable method of birth control during the study and for 3 months following the last dose of the investigational product * Female participants: women not of child-bearing potential due to menopause or surgical sterilization (at least 6 weeks post surgical bilateral oophorectomy, hysterectomy or tubal ligation) confirmed by medical history * Have a body mass index (BMI) of 18.5 to 40.0 kilograms/square meter (kg/m\^2), inclusive at the time of screening * Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator * Have venous access sufficient to allow for blood sampling as per the protocol * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study restrictions * Have given written informed consent on an informed consent form (ICF) approved by Lilly and the corresponding ethics committee (EC) or ethical review board (ERB) governing the site Part 1 only: * Have controlled mild to moderate hypertension (supine blood pressure \[BP\] less than or equal to 140/90 millimeter of mercury (mm Hg) at screening, or results with acceptable deviations that are judged not to be clinically significant by the investigator). * Males and females with stable medical problems (including Type 2 Diabetes Mellitus \[T2DM\]) that, in the investigator's opinion, will not significantly alter the disposition of the drug, will not place the participant at increased risk by participating in the study, and will not interfere with interpretation of the data may be included * Have been on oral antihypertensive medication (lisinopril daily \[QD\]) for at least 3 months prior to screening, have been on a stable dose for at least 1 month prior to screening, and are, in the investigator's opinion, able to safely adhere to a QD morning dosing regimen. Additional medication may be permitted as indicated T2DM Participants (Part 1 only): * Have T2DM controlled with diet or exercise alone or stable on a single oral agent antihyperglycemic medication (metformin, sulfonylureas, repaglinide, nateglinide, acarbose \[or other disaccharidase inhibitors\] or thiazolidinediones) for at least 3 weeks (3 months for thiazolidinediones) prior to admission * Have a hemoglobin A1c (HbA1c) value of 6.0% to 9.5% at screening or within 4 weeks prior to screening * Clinical laboratory test results within normal range or deemed clinically insignificant by the investigator. Abnormalities of serum glucose, serum lipids, urinary glucose, and urinary protein consistent with T2DM are acceptable Part 2 only: • Are overtly healthy, as determined by medical history and physical examination
Exclusion criteria
* Are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product; or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Have known allergies to Glucagon-like peptide-1 (GLP-1)-related compounds, including LY2189265, or any components of the formulation * Are participants who have previously completed or withdrawn from this study, or have taken part in any other study investigating LY2189265 or GLP-1-related compounds within the last 3 months * Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study * Have a history or presence of gastrointestinal disorder (including pancreatitis \[history of chronic pancreatitis or idiopathic acute pancreatitis\] or gall bladder disease) or gastrointestinal disease that impacts gastric emptying (GE) (e.g. gastric bypass surgery, pyloric stenosis) or could be aggravated by GLP-1 analogs (for example; esophageal reflux). Participants having had cholecystectomy (removal of gall bladder) in the past with no further sequelae, may be included in the study at the discretion of the screening physician * Have a history or presence of thyroid disease, unless have been on a stable dose of thyroxine replacement therapy for at least 1 month * Show history or evidence of significant active neuropsychiatric disease * Have personal or family history of medullary thyroid cancer (MTC) or a genetic condition that predisposes to MTC * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening * Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * Show evidence of hepatitis C and/or positive hepatitis C antibody * Show evidence of hepatitis B and/or positive hepatitis B surface antigen * Intend to start new concomitant medication during the study, including over-the-counter and herbal medication, use drugs that directly reduce gastrointestinal motility or who regularly use systemic corticosteroids, or potent, inhaled, or intranasal steroids known to have a high rate of systemic absorption * Have donated more than 500 milliliters (mL) of blood within the month prior to screening * Have a nondominant arm circumference of greater than 42 centimeters (cm) * Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females), or are unwilling to stop alcohol consumption from 48 hours before each admission until discharge from the unit, and to limit alcohol intake to a maximum of 2 units/day on all other days from screening through 48 hours prior to the follow-up visit. (1 unit = 12 ounces \[oz\] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits) * Are participants who, in the opinion of the investigator, are in any way unsuitable to participate in the study Part 1 only: • Have any medical conditions, medical history or are taking any medication which are contraindicated within the lisinopril product information leaflet Part 2 only: * Intend to use over-the-counter medication (with the exception of paracetamol and/or antacids) within 7 days prior to dosing or prescription medication (with the exception of vitamin/mineral supplements and/or hormone replacement therapy and/or thyroid replacement therapy) within 14 days prior to dosing of the investigational product * Have any medical conditions, medical history or are taking any medication which are contraindicated within the metoprolol product information leaflet
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Day -1, Day 4, Day 7 of Treatment 2 in Part 2 |
| Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril | Day -1, Day 3, Day 24 of Part 1 |
| Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril | Day -1, Day 3, Day 24 in Part 1 |
| Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Day -1, Day 4, Day 7 of Treatment 2 in Part 2 |
Secondary
| Measure | Time frame |
|---|---|
| Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Day -1, Day 3, Day 24 of Part 1 |
| Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Day -1, Day 3, Day 24 of Part 1 |
| Pharmacokinetics, Area Under the Concentration Curve (AUC) of Metoprolol When Administered With LY2189265 | Day 4 and Day 7 of Treatment 2 in Part 2 |
| Pharmacokinetics, Maximum Concentration (Cmax) of Metoprolol When Administered With LY2189265 | Day 4 and Day 7 of Treatment 2 in Part 2 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: LY2189265 + Lisinopril LY2189265 (dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), on Days 1, 8, 15, and 22 of Part 1 of the study.
Lisinopril: Dose as prescribed by participant's established course of therapy, oral, daily dosing throughout Part 1 of the study. | 23 |
| Part 1: Placebo + Lisinopril Placebo: 1.5 milligrams (mg), subcutaneous (SC), on Days 1, 8, 15, and 22 of Part 1 of the study.
Lisinopril: Dose as prescribed by participant's established course of therapy, oral, daily dosing throughout Part 1 of the study. | 8 |
| Part 2: LY2189265 + Metoprolol Crossover Participants received 2 treatments in Part 2 of the study:
Treatment 1: LY2189265 (dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), on Day 1
Treatment 2: LY2189265 (dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), on Day 5; Metoprolol: 100 mg, oral, on Days 1 through 7
Participants were randomized to 1 of 2 treatment sequences in Part 2 of the study:
Treatment Sequence A: Treatment 1, Treatment 2
Treatment Sequence B: Treatment 2, Treatment 1
There was a washout period of at least 21 days between the LY2189265 and metoprolol doses of each treatment period (Day 1 to Day 1 for Treatment Sequence A and Day 7 to Day 1 for Treatment Sequence B). | 20 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1 of Study | Adverse Event | 2 | 0 | 0 | 0 |
| Part 1 of Study | Physician Decision | 1 | 0 | 0 | 0 |
| Part 1 of Study | Protocol Violation | 1 | 2 | 0 | 0 |
| Part 2 of Study: First Intervention | Protocol Violation | 0 | 0 | 0 | 1 |
| Part 2 of Study: Second Intervention | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1: LY2189265 + Lisinopril | Total | Part 2: LY2189265 + Metoprolol Crossover | Part 1: Placebo + Lisinopril |
|---|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 10.4 | 51.8 years STANDARD_DEVIATION 14.6 | 44.6 years STANDARD_DEVIATION 16.7 | 54.0 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 48 Participants | 18 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 12 Participants | 8 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 11 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 5 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 23 Participants | 9 Participants | 5 Participants |
| Region of Enrollment United States | 23 participants | 51 participants | 20 participants | 8 participants |
| Sex: Female, Male Female | 11 Participants | 18 Participants | 6 Participants | 1 Participants |
| Sex: Female, Male Male | 12 Participants | 33 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 23 | 1 / 8 | 7 / 19 | 4 / 20 | 13 / 19 |
| serious Total, serious adverse events | 0 / 23 | 0 / 8 | 0 / 19 | 0 / 20 | 0 / 19 |
Outcome results
Primary
Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol
Time frame: Day -1, Day 4, Day 7 of Treatment 2 in Part 2
Population: Participants who received at least one dose of study drug (LY2189265 or metoprolol) with evaluable Part 2 ABPM blood pressure data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Systolic, Day -1 (Baseline) | 123.0 millimeter of mercury (mm Hg) | Standard Deviation 11.4 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Systolic, Day 4 (n=18) | 115.4 millimeter of mercury (mm Hg) | Standard Deviation 11.7 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Systolic, Day 7 | 116.2 millimeter of mercury (mm Hg) | Standard Deviation 10.4 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Diastolic, Day -1 (Baseline) | 72.8 millimeter of mercury (mm Hg) | Standard Deviation 7.3 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Diastolic, Day 4 (n=18) | 67.2 millimeter of mercury (mm Hg) | Standard Deviation 7.5 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Diastolic, Day 7 | 71.8 millimeter of mercury (mm Hg) | Standard Deviation 6.4 |
Primary
Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol
Time frame: Day -1, Day 4, Day 7 of Treatment 2 in Part 2
Population: Participants who received at least one dose of study drug (LY2189265 or metoprolol) with evaluable Part 2 ABPM heart rate data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Day -1 (Baseline) | 63.7 beats per minute (bpm) | Standard Deviation 9.6 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Day 4 (n=18) | 55.8 beats per minute (bpm) | Standard Deviation 9.4 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol | Day 7 | 69.4 beats per minute (bpm) | Standard Deviation 9 |
Primary
Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril
Time frame: Day -1, Day 3, Day 24 of Part 1
Population: Participants who received at least one dose of study drug (LY2189265 or placebo) with evaluable lisinopril AUC data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LY2189265 + Lisinopril | Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril | Day -1 (Baseline) | 1580 (nanograms*hours/milliliter)/milligram | Geometric Coefficient of Variation 55 |
| Part 1: LY2189265 + Lisinopril | Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril | Day 3 (n=22, 8) | 1660 (nanograms*hours/milliliter)/milligram | Geometric Coefficient of Variation 56 |
| Part 1: LY2189265 + Lisinopril | Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril | Day 24 (n=18, 6) | 1540 (nanograms*hours/milliliter)/milligram | Geometric Coefficient of Variation 52 |
| Part 1: Placebo + Lisinopril | Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril | Day -1 (Baseline) | 1740 (nanograms*hours/milliliter)/milligram | Geometric Coefficient of Variation 26 |
| Part 1: Placebo + Lisinopril | Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril | Day 3 (n=22, 8) | 1720 (nanograms*hours/milliliter)/milligram | Geometric Coefficient of Variation 28 |
| Part 1: Placebo + Lisinopril | Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril | Day 24 (n=18, 6) | 1390 (nanograms*hours/milliliter)/milligram | Geometric Coefficient of Variation 38 |
Primary
Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril
Time frame: Day -1, Day 3, Day 24 in Part 1
Population: Participants who received at least one dose of study drug (LY2189265 or placebo) with evaluable lisinopril Cmax data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LY2189265 + Lisinopril | Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril | Day -1 (Baseline) | 122 (nanograms per milliliter) per milligram | Geometric Coefficient of Variation 56 |
| Part 1: LY2189265 + Lisinopril | Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril | Day 3 (n=22, 8) | 114 (nanograms per milliliter) per milligram | Geometric Coefficient of Variation 55 |
| Part 1: LY2189265 + Lisinopril | Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril | Day 24 (n=18, 6) | 115 (nanograms per milliliter) per milligram | Geometric Coefficient of Variation 49 |
| Part 1: Placebo + Lisinopril | Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril | Day 24 (n=18, 6) | 110 (nanograms per milliliter) per milligram | Geometric Coefficient of Variation 39 |
| Part 1: Placebo + Lisinopril | Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril | Day -1 (Baseline) | 138 (nanograms per milliliter) per milligram | Geometric Coefficient of Variation 22 |
| Part 1: Placebo + Lisinopril | Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril | Day 3 (n=22, 8) | 138 (nanograms per milliliter) per milligram | Geometric Coefficient of Variation 25 |
Secondary
Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril
Time frame: Day -1, Day 3, Day 24 of Part 1
Population: Participants who received at least one dose of study drug (LY2189265 or placebo) with evaluable Part 1 ABPM blood pressure data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Systolic, Day -1 (Baseline) | 129.4 millimeter of mercury (mm Hg) | Standard Deviation 14.1 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Systolic, Day 3 (n=21, 6) | 125.3 millimeter of mercury (mm Hg) | Standard Deviation 11.5 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Systolic, Day 24 (n=18, 6) | 121.1 millimeter of mercury (mm Hg) | Standard Deviation 10.3 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Diastolic, Day -1 (Baseline) | 76.9 millimeter of mercury (mm Hg) | Standard Deviation 8.6 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Diastolic, Day 3 (n=21, 6) | 77.1 millimeter of mercury (mm Hg) | Standard Deviation 8.3 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Diastolic, Day 24 (n=18, 6) | 73.8 millimeter of mercury (mm Hg) | Standard Deviation 9.4 |
| Part 1: Placebo + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Diastolic, Day 3 (n=21, 6) | 72.6 millimeter of mercury (mm Hg) | Standard Deviation 5.1 |
| Part 1: Placebo + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Systolic, Day -1 (Baseline) | 130.1 millimeter of mercury (mm Hg) | Standard Deviation 14.9 |
| Part 1: Placebo + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Diastolic, Day -1 (Baseline) | 74.1 millimeter of mercury (mm Hg) | Standard Deviation 7.7 |
| Part 1: Placebo + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Systolic, Day 3 (n=21, 6) | 127.1 millimeter of mercury (mm Hg) | Standard Deviation 13.4 |
| Part 1: Placebo + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Diastolic, Day 24 (n=18, 6) | 71.2 millimeter of mercury (mm Hg) | Standard Deviation 7.8 |
| Part 1: Placebo + Lisinopril | Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Systolic, Day 24 (n=18, 6) | 123.8 millimeter of mercury (mm Hg) | Standard Deviation 16.2 |
Secondary
Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril
Time frame: Day -1, Day 3, Day 24 of Part 1
Population: Participants who received at least one dose of study drug (LY2189265 or placebo) with evaluable Part 1 ABPM heart rate data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Day -1 (Baseline) | 69.8 beats per minute (bpm) | Standard Deviation 8.9 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Day 3 (n=21, 6) | 78.3 beats per minute (bpm) | Standard Deviation 7.9 |
| Part 1: LY2189265 + Lisinopril | Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Day 24 (n=18, 6) | 77.1 beats per minute (bpm) | Standard Deviation 9 |
| Part 1: Placebo + Lisinopril | Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Day -1 (Baseline) | 68.9 beats per minute (bpm) | Standard Deviation 6.6 |
| Part 1: Placebo + Lisinopril | Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Day 3 (n=21, 6) | 69.3 beats per minute (bpm) | Standard Deviation 9 |
| Part 1: Placebo + Lisinopril | Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril | Day 24 (n=18, 6) | 71.6 beats per minute (bpm) | Standard Deviation 13.5 |
Secondary
Pharmacokinetics, Area Under the Concentration Curve (AUC) of Metoprolol When Administered With LY2189265
Time frame: Day 4 and Day 7 of Treatment 2 in Part 2
Population: Participants who received at least one dose of study drug (LY2189265 or metoprolol) with evaluable Part 2 metoprolol AUC data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LY2189265 + Lisinopril | Pharmacokinetics, Area Under the Concentration Curve (AUC) of Metoprolol When Administered With LY2189265 | Day 4 | 617 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 69 |
| Part 1: LY2189265 + Lisinopril | Pharmacokinetics, Area Under the Concentration Curve (AUC) of Metoprolol When Administered With LY2189265 | Day 7 (n=17) | 813 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 63 |
Secondary
Pharmacokinetics, Maximum Concentration (Cmax) of Metoprolol When Administered With LY2189265
Time frame: Day 4 and Day 7 of Treatment 2 in Part 2
Population: Participants who received at least one dose of study drug (LY2189265 or metoprolol) with evaluable Part 2 metoprolol Cmax data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: LY2189265 + Lisinopril | Pharmacokinetics, Maximum Concentration (Cmax) of Metoprolol When Administered With LY2189265 | Day 4 | 35.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 63 |
| Part 1: LY2189265 + Lisinopril | Pharmacokinetics, Maximum Concentration (Cmax) of Metoprolol When Administered With LY2189265 | Day 7 (n=19) | 47.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 66 |