Diabetes Mellitus, Type 2
Conditions
Keywords
Type 2 Diabetes, Diabetes, Ambulatory Blood Pressure Monitoring, ABPM, Blood Pressure, Heart Rate
Brief summary
The purpose of this study is to assess the effects of 2 doses of LY2189265 on blood pressure and heart rate using 24-hour ambulatory blood pressure monitoring (ABPM), in participants with type 2 diabetes mellitus treated with oral antihyperglycemic medications (OAMs).
Interventions
DRUGLY2189265
Administered as a subcutaneous injection once weekly for 26 weeks
DRUGPlacebo
Administered as a subcutaneous injection once weekly for 26 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes taking 1 or more oral diabetes medications and have taken these medications for at least 1 month prior to screening * Glycosylated hemoglobin (HbA1c) value ≥7% and ≤9.5% at screening * Mean blood pressure \>90/60 millimeters of mercury (mmHg) and \<140/90 mmHg at screening * If treated for hypertension, are taking 3 or less antihypertensive medications and have been taking these medications for at least 1 month prior to screening * Stable weight for 3 months prior to screening * Body mass index (BMI) greater than or equal to 23 kilogram-meter squared (kg/m\^2) * Willing to wear an ambulatory blood pressure monitoring device for at least 24 hours on multiple occasions * Women of childbearing potential must test negative for pregnancy and be willing to use a reliable method of birth control * Male participants must use a reliable method of birth control
Exclusion criteria
* Myocardial infarction, stroke, or hospitalization for heart failure within 3 months prior to screening, or heart failure Class III or IV at screening * Ongoing or history of frequent intermittent tachyarrhythmia * Resting heart rate \<60 beats per minute (bpm) or \>100 bpm at screening * Work rotating shifts or work during the hours of 2200 to 0700 * Chronic insulin therapy * Use of a glucagon-like peptide 1 (GLP-1) receptor agonist within 3 months prior to screening, or a dipeptidylpeptidase-IV (DPP-IV) inhibitor within 2 weeks prior to screening * Nondominant arm circumference \>42 centimeter (cm) * Use of drugs to promote weight loss * Chronic use of systemic steroids * Gastric emptying abnormality or bariatric surgery * Hepatitis, other liver disease, or alanine transaminase (ALT) \>3 times the upper limit of normal * Acute or chronic pancreatitis * Severe renal impairment * Active autoimmune disease or uncontrolled endocrine abnormality * Self or family history of thyroid cancer, medullary C-cell hyperplasia, or type 2A or 2B multiple endocrine neoplasia * Calcitonin value greater than or equal to 20 picograms per milliliter (pg/ml) at screening * Transplanted organ except corneal transplants * Active or untreated cancer or in remission \<5 years, except skin, in situ cervical, or prostate cancer * Sickle-cell disease, hemolytic anemia, or another hematological condition that may interfere with HbA1c testing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 16 Weeks in Mean 24-hour Systolic Blood Pressure (SBP) | Baseline, 16 weeks | Mean 24-hour systolic blood pressure (SBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 16 and 26 Weeks in Mean 24-hour Diastolic Blood Pressure (DBP) | Baseline, 16 and 26 weeks | Mean 24-hour diastolic blood pressure (DBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means of change from baseline was analyzed using mixed model repeated measures (MMRM) adjusted by baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Change From Baseline to 16 and 26 Weeks in Mean 24-Hour Heart Rate (HR) | Baseline, 16 and 26 weeks | Mean 24-hour heart rate (HR) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Heart rate measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Change From Baseline to 16 and 26 Weeks in Mean 24-hour Pulse Pressure | Baseline, 16 and 26 weeks | Mean 24-hour pulse pressure (PP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Pulse pressure (PP) measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Change From Baseline to 16 and 26 Weeks in Mean 24-hour Mean Arterial Pressure (MAP) | Baseline, 16 and 26 weeks | Mean 24-hour mean arterial pressure (MAP) was measured by a using 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Baseline, 16 and 26 weeks | Mean daytime and nighttime systolic blood pressure (SBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. Clinic SBP was measured in the clinic using the Omron HEM 907XL Blood Pressure monitor. |
| Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Baseline, 16 and 26 weeks | Mean daytime and nighttime diastolic blood pressure (DBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means of change from baseline was analyzed using mixed model repeated measures (MMRM) adjusted by baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. Clinic DBP was measured in the clinic using the Omron HEM 907XL Blood Pressure monitor. |
| Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Baseline, 16 and 26 weeks | Daytime and nighttime heart rate (HR) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Heart rate measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. Clinic HR was measured in the clinic using the Omron HEM 907XL Blood Pressure monitor. |
| Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Baseline, 16 and 26 weeks | Mean daytime and nighttime pulse pressure (PP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Pulse pressure (PP) measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Baseline, 16 and 26 weeks | Mean daytime and nighttime mean arterial pressure (MAP) was measured by a using 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Change From Baseline to 16 and 26 Weeks in Glycosylated Hemoglobin (HbA1c) | Baseline, 16 and 26 weeks | Glycosylated hemoglobin (HbA1c) is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Change From Baseline to 16 and 26 Weeks in Fasting Blood Glucose (FBG) | Baseline, 16 and 26 weeks | Fasting blood glucose (FBG) is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Change From Baseline to 26 Weeks in Mean 24-hour Systolic Blood Pressure (SBP) | Baseline, 26 weeks | Mean 24-hour systolic blood pressure (SBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Number of Participants With Treatment Emergent Adverse Events at 26 Weeks | Baseline through 26 weeks | A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Baseline, 16 and 26 weeks | Amylase (total and pancreas-derived) and lipase concentrations were measured. |
| Change From Baseline to 16 and 26 Weeks on Serum Calcitonin | Baseline, 16 and 26 weeks | — |
| Change From Baseline to 16 Weeks in High-Sensitivity C-Reactive Protein (Hs-CRP) | Baseline, 16 weeks | — |
| Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | Baseline, 16 and 26 weeks | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Number of Events of Adjudicated Pancreatitis up to 26 Weeks | Baseline through 26 weeks | The number of adjudicated (by an independent Clinical Endpoint Committee \[CEC\]) pancreatic events is summarized at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks | Baseline through 26 weeks | Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs to be adjudicated include myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Anti-LY2189265 Antibodies | Baseline, 16, 26, and 30 weeks | LY2189265 anti-drug antibodies (ADA) were assessed at baseline, 16 and 26 weeks, and at the safety follow-up visit 4 weeks after study drug discontinuation (30 weeks). The number of participants with initial postbaseline detection of treatment-emergent (defined as a 4-fold increase in the ADA titer from baseline) anti-drug (LY2189265) ADA at each time point were summarized. |
| Rate of Hypoglycemic Episodes | Baseline, 16 and 26 weeks | Hypoglycemic events (HE) were classified as severe (defined as an HE requiring assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as an HE with typical symptoms of hypoglycemia and a blood glucose level of ≤3.9 millimoles per liter \[mmol/L\]), asymptomatic (defined as an HE without typical symptoms of hypoglycemia but with a measured blood glucose of ≤3.9 mmol/L), nocturnal (defined as any HE occurring between bedtime and waking with a measured blood glucose of ≤3.9 mmol/L), or non-nocturnal. Hypoglycemia rate per 30 days was summarized at each visit by treatment group. The rate of hypoglycemia was analyzed using a generalized estimation equations model with a negative binomial distribution and a Logit link. Negative binomial mean was adjusted by treatment, visit, and visit by treatment interaction. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline to 16 and 26 Weeks in Body Weight | Baseline, 16 and 26 weeks | Least Squares (LS) means was calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. |
| Measurement of LY2189265 Drug Concentration for Pharmacokinetics - Area Under the Concentration Time Curve (AUC) | 4, 8, 12, 16, and 26 weeks | The population mean estimates and standard deviations were calculated for pharmacokinetic parameters (area under the concentration time curve \[AUC\] at steady state from time zero to 168 hours after study drug administration). Evaluable pharmacokinetic concentrations from the 4, 8, 12, 16, and 26 weeks timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state. |
| Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | Baseline and 16 and 26 weeks | Percentages of participants who achieved glycosylated hemoglobin (HbA1c) levels of \<7% or ≤6.5% were analyzed with Chi-squared test/Fisher's exact test. |
Countries
Argentina, Brazil, Canada, Czechia, Denmark, India, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1.5 Milligram (mg) LY2189265 LY2189265: 1.5 milligram (mg), subcutaneous (SC), once weekly (QW) for 26 weeks | 251 |
| 0.75 Milligram (mg) LY2189265 LY2189265: 0.75 milligram (mg), subcutaneous (SC), once weekly (QW) for 26 weeks | 254 |
| Placebo Placebo: subcutaneous (SC), once weekly (QW) for 26 weeks | 250 |
| Total | 755 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 22 | 6 | 11 |
| Overall Study | Entry Criteria Not Met | 1 | 1 | 2 |
| Overall Study | Lost to Follow-up | 2 | 4 | 5 |
| Overall Study | Physician Decision | 5 | 3 | 6 |
| Overall Study | Protocol Violation | 2 | 2 | 6 |
| Overall Study | Sponsor Decision | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 20 | 12 | 13 |
Baseline characteristics
| Characteristic | 0.75 Milligram (mg) LY2189265 | Total | Placebo | 1.5 Milligram (mg) LY2189265 |
|---|---|---|---|---|
| Age, Continuous | 57.05 years STANDARD_DEVIATION 10.17 | 56.48 years STANDARD_DEVIATION 10.27 | 56.43 years STANDARD_DEVIATION 10.5 | 55.96 years STANDARD_DEVIATION 10.14 |
| Body Mass Index (BMI) | 32.55 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 5.86 | 32.96 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 6.02 | 33.53 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 6.49 | 32.80 kilograms/square meters (kg/m^2) STANDARD_DEVIATION 5.66 |
| Body Weight | 90.45 kilogram (kg) STANDARD_DEVIATION 18.74 | 91.58 kilogram (kg) STANDARD_DEVIATION 19.6 | 93.90 kilogram (kg) STANDARD_DEVIATION 21.26 | 90.42 kilogram (kg) STANDARD_DEVIATION 18.58 |
| Duration of Diabetes | 8.99 years STANDARD_DEVIATION 6.39 | 8.34 years STANDARD_DEVIATION 5.86 | 8.40 years STANDARD_DEVIATION 5.76 | 7.61 years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 101 Participants | 287 Participants | 91 Participants | 95 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 153 Participants | 468 Participants | 159 Participants | 156 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Glycosylated Hemoglobin (HbA1c) | 7.91 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.73 | 7.93 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.76 | 7.94 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.78 | 7.93 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.76 |
| Mean Diastolic Blood Pressure (DBP) Mean 24-hour Diastolic Blood Pressure | 76.64 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.38 | 76.30 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.18 | 75.96 millimeters of mercury (mmHg) STANDARD_DEVIATION 7.79 | 76.29 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.39 |
| Mean Diastolic Blood Pressure (DBP) Mean Daytime Diastolic Blood Pressure | 79.35 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.81 | 78.99 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.61 | 78.68 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.27 | 78.93 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.77 |
| Mean Diastolic Blood Pressure (DBP) Mean Nighttime Diastolic Blood Pressure | 68.92 millimeters of mercury (mmHg) STANDARD_DEVIATION 9.47 | 68.65 millimeters of mercury (mmHg) STANDARD_DEVIATION 9.29 | 68.21 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.7 | 68.83 millimeters of mercury (mmHg) STANDARD_DEVIATION 9.7 |
| Mean Diastolic Blood Pressure (DBP) Mean Seated Diastolic Blood Pressure (Clinic) | 75.81 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.84 | 75.97 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.87 | 76.14 millimeters of mercury (mmHg) STANDARD_DEVIATION 9.19 | 75.95 millimeters of mercury (mmHg) STANDARD_DEVIATION 8.61 |
| Mean Heart Rate (HR) Mean 24-Hour Heart Rate | 79.01 beats per minute (bpm) STANDARD_DEVIATION 9.75 | 79.59 beats per minute (bpm) STANDARD_DEVIATION 10.18 | 79.91 beats per minute (bpm) STANDARD_DEVIATION 9.97 | 79.86 beats per minute (bpm) STANDARD_DEVIATION 10.83 |
| Mean Heart Rate (HR) Mean Daytime Heart Rate | 81.99 beats per minute (bpm) STANDARD_DEVIATION 10.45 | 82.47 beats per minute (bpm) STANDARD_DEVIATION 10.92 | 82.96 beats per minute (bpm) STANDARD_DEVIATION 10.69 | 82.47 beats per minute (bpm) STANDARD_DEVIATION 11.61 |
| Mean Heart Rate (HR) Mean Nighttime Heart Rate | 71.33 beats per minute (bpm) STANDARD_DEVIATION 9.94 | 72.10 beats per minute (bpm) STANDARD_DEVIATION 10.36 | 72.20 beats per minute (bpm) STANDARD_DEVIATION 10.35 | 72.78 beats per minute (bpm) STANDARD_DEVIATION 10.76 |
| Mean Heart Rate (HR) Mean Seated Heart Rate (Clinic) | 73.71 beats per minute (bpm) STANDARD_DEVIATION 9.31 | 74.37 beats per minute (bpm) STANDARD_DEVIATION 10.25 | 74.90 beats per minute (bpm) STANDARD_DEVIATION 10.56 | 74.50 beats per minute (bpm) STANDARD_DEVIATION 10.81 |
| Mean Systolic Blood Pressure (SBP) Mean 24-hour Systolic Blood Pressure | 132.08 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.97 | 131.36 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.13 | 131.13 millimeters of mercury (mmHg) STANDARD_DEVIATION 11.23 | 130.85 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.14 |
| Mean Systolic Blood Pressure (SBP) Mean Daytime Systolic Blood Pressure | 135.37 millimeters of mercury (mmHg) STANDARD_DEVIATION 13.36 | 134.48 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.48 | 134.15 millimeters of mercury (mmHg) STANDARD_DEVIATION 11.7 | 133.92 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.3 |
| Mean Systolic Blood Pressure (SBP) Mean Nighttime Systolic Blood Pressure | 122.10 millimeters of mercury (mmHg) STANDARD_DEVIATION 14.83 | 121.90 millimeters of mercury (mmHg) STANDARD_DEVIATION 14.02 | 121.92 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.82 | 121.68 millimeters of mercury (mmHg) STANDARD_DEVIATION 14.39 |
| Mean Systolic Blood Pressure (SBP) Mean Seated Systolic Blood Pressure (Clinic) | 127.42 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.79 | 126.98 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.96 | 126.81 millimeters of mercury (mmHg) STANDARD_DEVIATION 13.67 | 126.71 millimeters of mercury (mmHg) STANDARD_DEVIATION 12.44 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 24 Participants | 69 Participants | 23 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 66 Participants | 22 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 9 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 204 Participants | 608 Participants | 203 Participants | 201 Participants |
| Region of Enrollment Argentina | 28 participants | 82 participants | 25 participants | 29 participants |
| Region of Enrollment Brazil | 6 participants | 21 participants | 7 participants | 8 participants |
| Region of Enrollment Canada | 32 participants | 96 participants | 30 participants | 34 participants |
| Region of Enrollment Czech Republic | 12 participants | 37 participants | 13 participants | 12 participants |
| Region of Enrollment Denmark | 11 participants | 28 participants | 8 participants | 9 participants |
| Region of Enrollment India | 14 participants | 43 participants | 14 participants | 15 participants |
| Region of Enrollment Puerto Rico | 14 participants | 40 participants | 14 participants | 12 participants |
| Region of Enrollment United States | 137 participants | 408 participants | 139 participants | 132 participants |
| Sex: Female, Male Female | 123 Participants | 363 Participants | 119 Participants | 121 Participants |
| Sex: Female, Male Male | 131 Participants | 392 Participants | 131 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 164 / 251 | 161 / 254 | 163 / 250 |
| serious Total, serious adverse events | 12 / 251 | 8 / 254 | 8 / 250 |
Outcome results
Primary
Change From Baseline to 16 Weeks in Mean 24-hour Systolic Blood Pressure (SBP)
Mean 24-hour systolic blood pressure (SBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable blood pressure data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 Weeks in Mean 24-hour Systolic Blood Pressure (SBP) | -3.41 millimeters of mercury (mmHg) | Standard Error 0.61 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 Weeks in Mean 24-hour Systolic Blood Pressure (SBP) | -1.70 millimeters of mercury (mmHg) | Standard Error 0.58 |
| Placebo | Change From Baseline to 16 Weeks in Mean 24-hour Systolic Blood Pressure (SBP) | -0.63 millimeters of mercury (mmHg) | Standard Error 0.59 |
p-value: <0.00197.3% CI: [-4.58, -1]Mixed Models Analysis
p-value: <0.00197.3% CI: [-2.83, 0.68]Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: 0.149Mixed Models Analysis
Secondary
Anti-LY2189265 Antibodies
LY2189265 anti-drug antibodies (ADA) were assessed at baseline, 16 and 26 weeks, and at the safety follow-up visit 4 weeks after study drug discontinuation (30 weeks). The number of participants with initial postbaseline detection of treatment-emergent (defined as a 4-fold increase in the ADA titer from baseline) anti-drug (LY2189265) ADA at each time point were summarized.
Time frame: Baseline, 16, 26, and 30 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable anti-drug (LY2189265) antibodies (ADA) data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Anti-LY2189265 Antibodies | Week 26 | 1 participants |
| 1.5 Milligram (mg) LY2189265 | Anti-LY2189265 Antibodies | Week 16 | 2 participants |
| 1.5 Milligram (mg) LY2189265 | Anti-LY2189265 Antibodies | Week 30 | 0 participants |
| 0.75 Milligram (mg) LY2189265 | Anti-LY2189265 Antibodies | Week 26 | 3 participants |
| 0.75 Milligram (mg) LY2189265 | Anti-LY2189265 Antibodies | Week 16 | 0 participants |
| 0.75 Milligram (mg) LY2189265 | Anti-LY2189265 Antibodies | Week 30 | 1 participants |
| Placebo | Anti-LY2189265 Antibodies | Week 16 | 0 participants |
| Placebo | Anti-LY2189265 Antibodies | Week 30 | 0 participants |
| Placebo | Anti-LY2189265 Antibodies | Week 26 | 0 participants |
Secondary
Change From Baseline to 16 and 26 Weeks in Body Weight
Least Squares (LS) means was calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable body weight data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Body Weight | Week 16 | -1.84 kilogram (kg) | Standard Error 0.18 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Body Weight | Week 26 | -1.85 kilogram (kg) | Standard Error 0.23 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Body Weight | Week 16 | -0.83 kilogram (kg) | Standard Error 0.18 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Body Weight | Week 26 | -0.86 kilogram (kg) | Standard Error 0.22 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Body Weight | Week 26 | -0.08 kilogram (kg) | Standard Error 0.22 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Body Weight | Week 16 | -0.13 kilogram (kg) | Standard Error 0.18 |
p-value: <0.001Mixed Models Analysis
p-value: 0.005Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: 0.012Mixed Models Analysis
Secondary
Change From Baseline to 16 and 26 Weeks in Fasting Blood Glucose (FBG)
Fasting blood glucose (FBG) is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable fasting blood glucose data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Fasting Blood Glucose (FBG) | Week 16 | -2.05 millimoles per liter (mmol/L) | Standard Error 0.13 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Fasting Blood Glucose (FBG) | Week 26 | -1.67 millimoles per liter (mmol/L) | Standard Error 0.15 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Fasting Blood Glucose (FBG) | Week 16 | -1.94 millimoles per liter (mmol/L) | Standard Error 0.13 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Fasting Blood Glucose (FBG) | Week 26 | -1.66 millimoles per liter (mmol/L) | Standard Error 0.15 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Fasting Blood Glucose (FBG) | Week 16 | -0.30 millimoles per liter (mmol/L) | Standard Error 0.13 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Fasting Blood Glucose (FBG) | Week 26 | 0.00 millimoles per liter (mmol/L) | Standard Error 0.15 |
Secondary
Change From Baseline to 16 and 26 Weeks in Glycosylated Hemoglobin (HbA1c)
Glycosylated hemoglobin (HbA1c) is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable glycosylated hemoglobin (HbA1c) data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Glycosylated Hemoglobin (HbA1c) | Week 16 | -1.18 percentage of HbA1c | Standard Error 0.06 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Glycosylated Hemoglobin (HbA1c) | Week 26 | -1.01 percentage of HbA1c | Standard Error 0.07 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Glycosylated Hemoglobin (HbA1c) | Week 16 | -1.04 percentage of HbA1c | Standard Error 0.05 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Glycosylated Hemoglobin (HbA1c) | Week 26 | -0.89 percentage of HbA1c | Standard Error 0.06 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Glycosylated Hemoglobin (HbA1c) | Week 16 | -0.06 percentage of HbA1c | Standard Error 0.05 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Glycosylated Hemoglobin (HbA1c) | Week 26 | -0.02 percentage of HbA1c | Standard Error 0.06 |
Secondary
Change From Baseline to 16 and 26 Weeks in Mean 24-hour Diastolic Blood Pressure (DBP)
Mean 24-hour diastolic blood pressure (DBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means of change from baseline was analyzed using mixed model repeated measures (MMRM) adjusted by baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable diastolic blood pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Diastolic Blood Pressure (DBP) | Mean 24-Hour, Week 16 | -0.23 millimeters of mercury (mmHg)] | Standard Error 0.38 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Diastolic Blood Pressure (DBP) | Mean 24-Hour, Week 26 | 0.26 millimeters of mercury (mmHg)] | Standard Error 0.4 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Diastolic Blood Pressure (DBP) | Mean 24-Hour, Week 16 | -0.13 millimeters of mercury (mmHg)] | Standard Error 0.37 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Diastolic Blood Pressure (DBP) | Mean 24-Hour, Week 26 | -0.09 millimeters of mercury (mmHg)] | Standard Error 0.38 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Diastolic Blood Pressure (DBP) | Mean 24-Hour, Week 16 | -0.55 millimeters of mercury (mmHg)] | Standard Error 0.37 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Diastolic Blood Pressure (DBP) | Mean 24-Hour, Week 26 | -0.24 millimeters of mercury (mmHg)] | Standard Error 0.39 |
p-value: <0.00197.3% CI: [-0.8, 1.43]Mixed Models Analysis
p-value: <0.00197.3% CI: [-0.67, 1.52]Mixed Models Analysis
p-value: 0.87Mixed Models Analysis
p-value: 0.915Mixed Models Analysis
p-value: <0.00197.3% CI: [-0.68, 1.68]Mixed Models Analysis
p-value: <0.00197.3% CI: [-1, 1.31]Mixed Models Analysis
p-value: 0.929Mixed Models Analysis
p-value: 0.776Mixed Models Analysis
Secondary
Change From Baseline to 16 and 26 Weeks in Mean 24-Hour Heart Rate (HR)
Mean 24-hour heart rate (HR) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Heart rate measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable heart rate data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-Hour Heart Rate (HR) | Mean 24-Hour HR, Week 16 | 3.70 beats per minute (bpm) | Standard Error 0.45 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-Hour Heart Rate (HR) | Mean 24-Hour HR, Week 26 | 4.18 beats per minute (bpm) | Standard Error 0.47 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-Hour Heart Rate (HR) | Mean 24-Hour HR, Week 16 | 2.48 beats per minute (bpm) | Standard Error 0.43 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-Hour Heart Rate (HR) | Mean 24-Hour HR, Week 26 | 1.94 beats per minute (bpm) | Standard Error 0.46 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean 24-Hour Heart Rate (HR) | Mean 24-Hour HR, Week 16 | 0.86 beats per minute (bpm) | Standard Error 0.44 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean 24-Hour Heart Rate (HR) | Mean 24-Hour HR, Week 26 | 0.68 beats per minute (bpm) | Standard Error 0.47 |
p-value: 0.55697.3% CI: [1.52, 4.16]Mixed Models Analysis
p-value: 0.01897.3% CI: [0.32, 2.92]Mixed Models Analysis
p-value: 1Mixed Models Analysis
p-value: 0.90497.3% CI: [2.1, 4.91]Mixed Models Analysis
p-value: 0.00597.3% CI: [-0.13, 2.64]Mixed Models Analysis
p-value: 0.996Mixed Models Analysis
Secondary
Change From Baseline to 16 and 26 Weeks in Mean 24-hour Mean Arterial Pressure (MAP)
Mean 24-hour mean arterial pressure (MAP) was measured by a using 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable mean arterial pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Mean Arterial Pressure (MAP) | Week 16 | -1.31 millimeters of mercury (mmHg) | Standard Error 0.43 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Mean Arterial Pressure (MAP) | Week 26 | -0.74 millimeters of mercury (mmHg) | Standard Error 0.44 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Mean Arterial Pressure (MAP) | Week 16 | -0.65 millimeters of mercury (mmHg) | Standard Error 0.42 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Mean Arterial Pressure (MAP) | Week 26 | -0.57 millimeters of mercury (mmHg) | Standard Error 0.42 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Mean Arterial Pressure (MAP) | Week 16 | -0.60 millimeters of mercury (mmHg) | Standard Error 0.42 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Mean Arterial Pressure (MAP) | Week 26 | -0.15 millimeters of mercury (mmHg) | Standard Error 0.43 |
p-value: 0.21895% CI: [-1.84, 0.42]Mixed Models Analysis
p-value: 0.93195% CI: [-1.16, 1.06]Mixed Models Analysis
p-value: 0.31595% CI: [-1.72, 0.55]Mixed Models Analysis
p-value: 0.46595% CI: [-1.54, 0.7]Mixed Models Analysis
Secondary
Change From Baseline to 16 and 26 Weeks in Mean 24-hour Pulse Pressure
Mean 24-hour pulse pressure (PP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Pulse pressure (PP) measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable pulse pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Pulse Pressure | Mean 24-Hour PP, Week 16 | -3.07 millimeters of mercury (mmHg) | Standard Error 0.36 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Pulse Pressure | Mean 24-Hour PP, Week 26 | -2.64 millimeters of mercury (mmHg) | Standard Error 0.38 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Pulse Pressure | Mean 24-Hour PP, Week 16 | -1.60 millimeters of mercury (mmHg) | Standard Error 0.35 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Pulse Pressure | Mean 24-Hour PP, Week 26 | -1.53 millimeters of mercury (mmHg) | Standard Error 0.37 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Pulse Pressure | Mean 24-Hour PP, Week 16 | -0.02 millimeters of mercury (mmHg) | Standard Error 0.36 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean 24-hour Pulse Pressure | Mean 24-Hour PP, Week 26 | 0.46 millimeters of mercury (mmHg) | Standard Error 0.37 |
p-value: <0.00195% CI: [-4, -2.09]Mixed Models Analysis
p-value: 0.00195% CI: [-2.51, -0.64]Mixed Models Analysis
p-value: <0.00195% CI: [-4.1, -2.09]Mixed Models Analysis
p-value: <0.00195% CI: [-2.98, -1]Mixed Models Analysis
Secondary
Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP)
Mean daytime and nighttime mean arterial pressure (MAP) was measured by a using 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable mean arterial pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Daytime MAP, Week 16 | -1.30 millimeters of mercury (mmHg) | Standard Error 0.48 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Daytime MAP, Week 26 | -0.51 millimeters of mercury (mmHg) | Standard Error 0.49 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Nighttime MAP, Week 16 | -0.80 millimeters of mercury (mmHg) | Standard Error 0.56 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Nighttime MAP, Week 26 | -0.96 millimeters of mercury (mmHg) | Standard Error 0.57 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Nighttime MAP, Week 26 | -0.76 millimeters of mercury (mmHg) | Standard Error 0.54 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Daytime MAP, Week 16 | -0.42 millimeters of mercury (mmHg) | Standard Error 0.46 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Nighttime MAP, Week 16 | -0.59 millimeters of mercury (mmHg) | Standard Error 0.53 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Daytime MAP, Week 26 | -0.42 millimeters of mercury (mmHg) | Standard Error 0.47 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Nighttime MAP, Week 26 | -0.50 millimeters of mercury (mmHg) | Standard Error 0.56 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Daytime MAP, Week 26 | 0.05 millimeters of mercury (mmHg) | Standard Error 0.48 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Nighttime MAP, Week 16 | -1.11 millimeters of mercury (mmHg) | Standard Error 0.54 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Mean Arterial Pressure (MAP) | Mean Daytime MAP, Week 16 | -0.33 millimeters of mercury (mmHg) | Standard Error 0.47 |
p-value: 0.12895% CI: [-2.22, 0.28]Mixed Models Analysis
p-value: 0.88395% CI: [-1.32, 1.13]Mixed Models Analysis
p-value: 0.3995% CI: [-1.84, 0.72]Mixed Models Analysis
p-value: 0.46395% CI: [-1.72, 0.79]Mixed Models Analysis
p-value: 0.67195% CI: [-1.13, 1.76]Mixed Models Analysis
p-value: 0.47195% CI: [-0.9, 1.95]Mixed Models Analysis
p-value: 0.54395% CI: [-1.95, 1.03]Mixed Models Analysis
p-value: 0.72895% CI: [-1.72, 1.2]Mixed Models Analysis
Secondary
Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure
Mean daytime and nighttime pulse pressure (PP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Pulse pressure (PP) measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable pulse pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Daytime PP, Week 16 | -3.46 millimeters of mercury (mmHg) | Standard Error 0.4 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Daytime PP, Week 26 | -2.90 millimeters of mercury (mmHg) | Standard Error 0.42 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Nighttime PP, Week 16 | -2.23 millimeters of mercury (mmHg) | Standard Error 0.45 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Nighttime PP, Week 26 | -2.09 millimeters of mercury (mmHg) | Standard Error 0.43 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Nighttime PP, Week 26 | -0.96 millimeters of mercury (mmHg) | Standard Error 0.41 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Daytime PP, Week 16 | -1.76 millimeters of mercury (mmHg) | Standard Error 0.38 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Nighttime PP, Week 16 | -0.92 millimeters of mercury (mmHg) | Standard Error 0.43 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Daytime PP, Week 26 | -1.62 millimeters of mercury (mmHg) | Standard Error 0.41 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Nighttime PP, Week 26 | 0.65 millimeters of mercury (mmHg) | Standard Error 0.42 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Daytime PP, Week 26 | 0.51 millimeters of mercury (mmHg) | Standard Error 0.42 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Nighttime PP, Week 16 | 0.02 millimeters of mercury (mmHg) | Standard Error 0.44 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime and Nighttime Pulse Pressure | Mean Daytime PP, Week 16 | 0.01 millimeters of mercury (mmHg) | Standard Error 0.39 |
p-value: <0.00195% CI: [-4.5, -2.43]Mixed Models Analysis
p-value: <0.00195% CI: [-2.79, -0.75]Mixed Models Analysis
p-value: <0.00195% CI: [-4.52, -2.28]Mixed Models Analysis
p-value: <0.00195% CI: [-3.23, -1.03]Mixed Models Analysis
p-value: <0.00195% CI: [-3.43, -1.07]Mixed Models Analysis
p-value: 0.11395% CI: [-2.09, 0.22]Mixed Models Analysis
p-value: <0.00195% CI: [-3.86, -1.62]Mixed Models Analysis
p-value: 0.00495% CI: [-2.72, -0.51]Mixed Models Analysis
Secondary
Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP)
Mean daytime and nighttime diastolic blood pressure (DBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means of change from baseline was analyzed using mixed model repeated measures (MMRM) adjusted by baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. Clinic DBP was measured in the clinic using the Omron HEM 907XL Blood Pressure monitor.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable diastolic blood pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Daytime DBP, Week 16 (n=247, n=251, n=249) | -0.09 millimeters of mercury (mmHg) | Standard Error 0.43 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Daytime DBP, Week 26 (n=247, n=251, n=249) | 0.52 millimeters of mercury (mmHg) | Standard Error 0.43 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Nighttime DBP, Week 16 (n=247, n=251, n=249) | -0.01 millimeters of mercury (mmHg) | Standard Error 0.49 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Nighttime DBP, Week 26 (n=247, n=251, n=249) | -0.22 millimeters of mercury (mmHg) | Standard Error 0.51 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Clinic DBP, Week 16 (n=251, n=254, n=250) | -0.21 millimeters of mercury (mmHg) | Standard Error 0.52 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Clinic DBP, Week 26 (n=251, n=254, n=250) | 0.59 millimeters of mercury (mmHg) | Standard Error 0.5 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Clinic DBP, Week 26 (n=251, n=254, n=250) | 0.69 millimeters of mercury (mmHg) | Standard Error 0.48 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Daytime DBP, Week 16 (n=247, n=251, n=249) | 0.14 millimeters of mercury (mmHg) | Standard Error 0.41 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Nighttime DBP, Week 26 (n=247, n=251, n=249) | -0.42 millimeters of mercury (mmHg) | Standard Error 0.5 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Clinic DBP, Week 16 (n=251, n=254, n=250) | 0.76 millimeters of mercury (mmHg) | Standard Error 0.5 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Daytime DBP, Week 26 (n=247, n=251, n=249) | 0.08 millimeters of mercury (mmHg) | Standard Error 0.41 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Nighttime DBP, Week 16 (n=247, n=251, n=249) | -0.28 millimeters of mercury (mmHg) | Standard Error 0.48 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Daytime DBP, Week 26 (n=247, n=251, n=249) | -0.07 millimeters of mercury (mmHg) | Standard Error 0.42 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Nighttime DBP, Week 16 (n=247, n=251, n=249) | -1.10 millimeters of mercury (mmHg) | Standard Error 0.48 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Clinic DBP, Week 26 (n=251, n=254, n=250) | 0.61 millimeters of mercury (mmHg) | Standard Error 0.49 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Nighttime DBP, Week 26 (n=247, n=251, n=249) | -0.69 millimeters of mercury (mmHg) | Standard Error 0.51 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Daytime DBP, Week 16 (n=247, n=251, n=249) | -0.30 millimeters of mercury (mmHg) | Standard Error 0.42 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Diastolic Blood Pressure (DBP) | Mean Clinic DBP, Week 16 (n=251, n=254, n=250) | -0.21 millimeters of mercury (mmHg) | Standard Error 0.51 |
p-value: 0.71795% CI: [-0.91, 1.32]Mixed Models Analysis
p-value: 0.42795% CI: [-0.65, 1.54]Mixed Models Analysis
p-value: 0.395% CI: [-0.53, 1.73]Mixed Models Analysis
p-value: 0.78895% CI: [-0.96, 1.26]Mixed Models Analysis
p-value: 0.09895% CI: [-0.2, 2.37]Mixed Models Analysis
p-value: 0.20395% CI: [-0.44, 2.08]Mixed Models Analysis
p-value: 0.49395% CI: [-0.88, 1.82]Mixed Models Analysis
p-value: 0.69295% CI: [-1.06, 1.6]Mixed Models Analysis
p-value: 0.99Mixed Models Analysis
p-value: 0.173Mixed Models Analysis
p-value: 0.972Mixed Models Analysis
p-value: 0.904Mixed Models Analysis
Secondary
Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR)
Daytime and nighttime heart rate (HR) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Heart rate measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. Clinic HR was measured in the clinic using the Omron HEM 907XL Blood Pressure monitor.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable heart rate data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Daytime HR, Week 16 (n=247, n=251, n=249) | 3.56 beats per minute (bpm) | Standard Error 0.5 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Daytime HR, Week 26 (n=247, n=251, n=249) | 4.24 beats per minute (bpm) | Standard Error 0.51 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Nighttime HR, Week 16 (n=247, n=251, n=249) | 4.60 beats per minute (bpm) | Standard Error 0.51 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Nighttime HR, Week 26 (n=247, n=251, n=249) | 4.76 beats per minute (bpm) | Standard Error 0.57 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Clinic HR, Week 16 (n=251, n=254, n=250) | 3.97 beats per minute (bpm) | Standard Error 0.49 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Clinic HR, Week 26 (n=251, n=254, n=250) | 4.89 beats per minute (bpm) | Standard Error 0.54 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Clinic HR, Week 26 (n=251, n=254, n=250) | 1.93 beats per minute (bpm) | Standard Error 0.52 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Daytime HR, Week 16 (n=247, n=251, n=249) | 2.22 beats per minute (bpm) | Standard Error 0.49 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Nighttime HR, Week 26 (n=247, n=251, n=249) | 3.01 beats per minute (bpm) | Standard Error 0.54 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Clinic HR, Week 16 (n=251, n=254, n=250) | 2.11 beats per minute (bpm) | Standard Error 0.48 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Daytime HR, Week 26 (n=247, n=251, n=249) | 1.59 beats per minute (bpm) | Standard Error 0.49 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Nighttime HR, Week 16 (n=247, n=251, n=249) | 3.43 beats per minute (bpm) | Standard Error 0.49 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Daytime HR, Week 26 (n=247, n=251, n=249) | 0.67 beats per minute (bpm) | Standard Error 0.5 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Nighttime HR, Week 16 (n=247, n=251, n=249) | 0.65 beats per minute (bpm) | Standard Error 0.5 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Clinic HR, Week 26 (n=251, n=254, n=250) | -0.11 beats per minute (bpm) | Standard Error 0.53 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Nighttime HR, Week 26 (n=247, n=251, n=249) | 0.77 beats per minute (bpm) | Standard Error 0.55 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Daytime HR, Week 16 (n=247, n=251, n=249) | 1.07 beats per minute (bpm) | Standard Error 0.49 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Heart Rate (HR) | Mean Clinic HR, Week 16 (n=251, n=254, n=250) | 0.46 beats per minute (bpm) | Standard Error 0.48 |
p-value: <0.00195% CI: [1.17, 3.8]Mixed Models Analysis
p-value: 0.0895% CI: [-0.14, 2.45]Mixed Models Analysis
p-value: <0.00195% CI: [2.23, 4.91]Mixed Models Analysis
p-value: 0.16895% CI: [-0.39, 2.24]Mixed Models Analysis
p-value: <0.00195% CI: [2.62, 5.28]Mixed Models Analysis
p-value: <0.00195% CI: [1.47, 4.09]Mixed Models Analysis
p-value: <0.00195% CI: [2.49, 5.47]Mixed Models Analysis
p-value: 0.00395% CI: [0.78, 3.7]Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: 0.014Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: 0.005Mixed Models Analysis
Secondary
Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP)
Mean daytime and nighttime systolic blood pressure (SBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension. Clinic SBP was measured in the clinic using the Omron HEM 907XL Blood Pressure monitor.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable systolic blood pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Daytime SBP, Week 16 (n=247, n=251, n=249) | -3.67 millimeters of mercury (mmHg) | Standard Error 0.66 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Daytime SBP, Week 26 (n=247, n=251, n=249) | -2.52 millimeters of mercury (mmHg) | Standard Error 0.68 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Nighttime SBP, Week 16 (n=247, n=251, n=249) | -2.32 millimeters of mercury (mmHg) | Standard Error 0.76 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Nighttime SBP, Week 26 (n=247, n=251, n=249) | -2.40 millimeters of mercury (mmHg) | Standard Error 0.75 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Clinic SBP, Week 16 (n=251, n=254, n=250) | -2.33 millimeters of mercury (mmHg) | Standard Error 0.75 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Clinic SBP, Week 26 (n=251, n=254, n=250) | -2.29 millimeters of mercury (mmHg) | Standard Error 0.77 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Clinic SBP, Week 26 (n=251, n=254, n=250) | -0.74 millimeters of mercury (mmHg) | Standard Error 0.74 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Daytime SBP, Week 16 (n=247, n=251, n=249) | -1.57 millimeters of mercury (mmHg) | Standard Error 0.63 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Nighttime SBP, Week 26 (n=247, n=251, n=249) | -1.43 millimeters of mercury (mmHg) | Standard Error 0.72 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Clinic SBP, Week 16 (n=251, n=254, n=250) | -1.26 millimeters of mercury (mmHg) | Standard Error 0.72 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Daytime SBP, Week 26 (n=247, n=251, n=249) | -1.47 millimeters of mercury (mmHg) | Standard Error 0.65 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Nighttime SBP, Week 16 (n=247, n=251, n=249) | -1.23 millimeters of mercury (mmHg) | Standard Error 0.73 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Daytime SBP, Week 26 (n=247, n=251, n=249) | 0.35 millimeters of mercury (mmHg) | Standard Error 0.67 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Nighttime SBP, Week 16 (n=247, n=251, n=249) | -1.08 millimeters of mercury (mmHg) | Standard Error 0.74 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Clinic SBP, Week 26 (n=251, n=254, n=250) | 0.40 millimeters of mercury (mmHg) | Standard Error 0.75 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Nighttime SBP, Week 26 (n=247, n=251, n=249) | -0.05 millimeters of mercury (mmHg) | Standard Error 0.73 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Daytime SBP, Week 16 (n=247, n=251, n=249) | -0.34 millimeters of mercury (mmHg) | Standard Error 0.64 |
| Placebo | Change From Baseline to 16 and 26 Weeks in Mean Daytime, Nighttime, and Clinic Systolic Blood Pressure (SBP) | Mean Clinic SBP, Week 16 (n=251, n=254, n=250) | -0.73 millimeters of mercury (mmHg) | Standard Error 0.73 |
p-value: <0.00195% CI: [-5.04, -1.61]Mixed Models Analysis
p-value: 0.15395% CI: [-2.91, 0.46]Mixed Models Analysis
p-value: 0.00295% CI: [-4.66, -1.09]Mixed Models Analysis
p-value: 0.04295% CI: [-3.57, -0.07]Mixed Models Analysis
p-value: 0.22195% CI: [-3.23, 0.75]Mixed Models Analysis
p-value: 0.88495% CI: [-2.1, 1.81]Mixed Models Analysis
p-value: 0.1995% CI: [-4.31, -0.39]Mixed Models Analysis
p-value: 0.15995% CI: [-3.31, 0.54]Mixed Models Analysis
p-value: 0.122Mixed Models Analysis
p-value: 0.601Mixed Models Analysis
p-value: 0.012Mixed Models Analysis
p-value: 0.274Mixed Models Analysis
Secondary
Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable Fridericia-corrected QT (QTcF) or PR interval change from baseline data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval, Week 16 (n=248, n=250, n=246) | -2.31 milliseconds (msec) | Standard Error 0.97 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval, Week 26 (n=248, n=250, n=246) | -1.73 milliseconds (msec) | Standard Error 0.96 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval, Week 16 (n=248, n=250, n=244) | 4.96 milliseconds (msec) | Standard Error 0.98 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval, Week 26 (n=248, n=250, n=244) | 3.32 milliseconds (msec) | Standard Error 0.86 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval, Week 26 (n=248, n=250, n=244) | 3.17 milliseconds (msec) | Standard Error 0.81 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval, Week 16 (n=248, n=250, n=246) | -0.96 milliseconds (msec) | Standard Error 0.91 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval, Week 16 (n=248, n=250, n=244) | 3.67 milliseconds (msec) | Standard Error 0.92 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval, Week 26 (n=248, n=250, n=246) | -0.93 milliseconds (msec) | Standard Error 0.92 |
| Placebo | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval, Week 26 (n=248, n=250, n=244) | -1.98 milliseconds (msec) | Standard Error 0.84 |
| Placebo | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval, Week 26 (n=248, n=250, n=246) | 1.26 milliseconds (msec) | Standard Error 0.94 |
| Placebo | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval, Week 16 (n=248, n=250, n=244) | 0.01 milliseconds (msec) | Standard Error 0.95 |
| Placebo | Change From Baseline to 16 and 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval, Week 16 (n=248, n=250, n=246) | 1.06 milliseconds (msec) | Standard Error 0.93 |
Secondary
Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes
Amylase (total and pancreas-derived) and lipase concentrations were measured.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable pancreatic enzyme data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Total, Week 16 (n=214, 227, 224) | 6.00 units per liter |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Total, Week 26 (n=205, 220, 209) | 7.00 units per liter |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived, Wk 16 (n=213, 227, 224) | 4.00 units per liter |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived, Wk 26 (n=204, 220, 209) | 5.00 units per liter |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Lipase, Week 16 (n=214, 227, 224) | 4.00 units per liter |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Lipase, Week 26 (n=205, 220, 209) | 6.00 units per liter |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Lipase, Week 26 (n=205, 220, 209) | 5.00 units per liter |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Total, Week 16 (n=214, 227, 224) | 5.00 units per liter |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived, Wk 26 (n=204, 220, 209) | 3.50 units per liter |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Lipase, Week 16 (n=214, 227, 224) | 3.00 units per liter |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Total, Week 26 (n=205, 220, 209) | 4.00 units per liter |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived, Wk 16 (n=213, 227, 224) | 3.00 units per liter |
| Placebo | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Total, Week 26 (n=205, 220, 209) | 0.00 units per liter |
| Placebo | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived, Wk 16 (n=213, 227, 224) | 1.00 units per liter |
| Placebo | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Lipase, Week 26 (n=205, 220, 209) | 0.00 units per liter |
| Placebo | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived, Wk 26 (n=204, 220, 209) | 1.00 units per liter |
| Placebo | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Amylase, Total, Week 16 (n=214, 227, 224) | 0.00 units per liter |
| Placebo | Change From Baseline to 16 and 26 Weeks on Pancreatic Enzymes | Lipase, Week 16 (n=214, 227, 224) | -1.00 units per liter |
Secondary
Change From Baseline to 16 and 26 Weeks on Serum Calcitonin
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable serum calcitonin data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Serum Calcitonin | Week 26 (n=202, n=220, n=209) | -0.19 picograms per milliliter (pg/mL) | Standard Deviation 1.73 |
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Serum Calcitonin | Week 16 (n=213, n=223, n=223) | -0.30 picograms per milliliter (pg/mL) | Standard Deviation 1.87 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Serum Calcitonin | Week 16 (n=213, n=223, n=223) | -0.03 picograms per milliliter (pg/mL) | Standard Deviation 1.81 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 and 26 Weeks on Serum Calcitonin | Week 26 (n=202, n=220, n=209) | 0.02 picograms per milliliter (pg/mL) | Standard Deviation 2.04 |
| Placebo | Change From Baseline to 16 and 26 Weeks on Serum Calcitonin | Week 16 (n=213, n=223, n=223) | -0.39 picograms per milliliter (pg/mL) | Standard Deviation 1.24 |
| Placebo | Change From Baseline to 16 and 26 Weeks on Serum Calcitonin | Week 26 (n=202, n=220, n=209) | -0.05 picograms per milliliter (pg/mL) | Standard Deviation 2.38 |
Secondary
Change From Baseline to 16 Weeks in High-Sensitivity C-Reactive Protein (Hs-CRP)
Time frame: Baseline, 16 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable High-Sensitivity C-Reactive Protein (hs-CRP) data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 16 Weeks in High-Sensitivity C-Reactive Protein (Hs-CRP) | -0.79 milligram per liter (mg/L) | Standard Deviation 4.91 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 16 Weeks in High-Sensitivity C-Reactive Protein (Hs-CRP) | -0.20 milligram per liter (mg/L) | Standard Deviation 7.96 |
| Placebo | Change From Baseline to 16 Weeks in High-Sensitivity C-Reactive Protein (Hs-CRP) | 0.29 milligram per liter (mg/L) | Standard Deviation 6.73 |
Secondary
Change From Baseline to 26 Weeks in Mean 24-hour Systolic Blood Pressure (SBP)
Mean 24-hour systolic blood pressure (SBP) was measured by using a 24-hour ambulatory blood pressure monitoring (ABPM) device attached to the participant's nondominant arm. Ambulatory blood pressure measurements were recorded every 20 minutes during the daytime (0700 to 2200 hours) and every 30 minutes during the nighttime hours (2200 to 0700), as preprogrammed into the device. For statistical analyses, diurnal hours were defined as 0800 to 2100 and nocturnal hours were defined as 0000 to 0600. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for baseline, pooled sites, treatment, visit, treatment-by-visit interaction, and the stratified variable of diagnosis of hypertension.
Time frame: Baseline, 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable systolic blood pressure data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Change From Baseline to 26 Weeks in Mean 24-hour Systolic Blood Pressure (SBP) | -2.51 millimeters of mercury (mmHg) | Standard Error 0.63 |
| 0.75 Milligram (mg) LY2189265 | Change From Baseline to 26 Weeks in Mean 24-hour Systolic Blood Pressure (SBP) | -1.56 millimeters of mercury (mmHg) | Standard Error 0.6 |
| Placebo | Change From Baseline to 26 Weeks in Mean 24-hour Systolic Blood Pressure (SBP) | 0.15 millimeters of mercury (mmHg) | Standard Error 0.62 |
p-value: <0.00197.3% CI: [-4.53, -0.79]Mixed Models Analysis
p-value: <0.00197.3% CI: [-3.54, 0.12]Mixed Models Analysis
p-value: 0.002Mixed Models Analysis
p-value: 0.36Mixed Models Analysis
Secondary
Measurement of LY2189265 Drug Concentration for Pharmacokinetics - Area Under the Concentration Time Curve (AUC)
The population mean estimates and standard deviations were calculated for pharmacokinetic parameters (area under the concentration time curve \[AUC\] at steady state from time zero to 168 hours after study drug administration). Evaluable pharmacokinetic concentrations from the 4, 8, 12, 16, and 26 weeks timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.
Time frame: 4, 8, 12, 16, and 26 weeks
Population: Participants who received at least one dose of LY2189265 with evaluable LY2189265 concentration data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Measurement of LY2189265 Drug Concentration for Pharmacokinetics - Area Under the Concentration Time Curve (AUC) | 11208 nanograms*hour per liter (ng*h/L) | Standard Deviation 3744 |
| 0.75 Milligram (mg) LY2189265 | Measurement of LY2189265 Drug Concentration for Pharmacokinetics - Area Under the Concentration Time Curve (AUC) | 5998 nanograms*hour per liter (ng*h/L) | Standard Deviation 2003 |
Secondary
Number of Events of Adjudicated Pancreatitis up to 26 Weeks
The number of adjudicated (by an independent Clinical Endpoint Committee \[CEC\]) pancreatic events is summarized at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Number of Events of Adjudicated Pancreatitis up to 26 Weeks | 0 events |
| 0.75 Milligram (mg) LY2189265 | Number of Events of Adjudicated Pancreatitis up to 26 Weeks | 0 events |
| Placebo | Number of Events of Adjudicated Pancreatitis up to 26 Weeks | 0 events |
Secondary
Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks
Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs to be adjudicated include myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks | Any fatal cardiovascular event | 0 participants |
| 1.5 Milligram (mg) LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks | Any cardiovascular event | 1 participants |
| 1.5 Milligram (mg) LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks | Any non-fatal cardiovascular event | 1 participants |
| 0.75 Milligram (mg) LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks | Any fatal cardiovascular event | 0 participants |
| 0.75 Milligram (mg) LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks | Any cardiovascular event | 1 participants |
| 0.75 Milligram (mg) LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks | Any non-fatal cardiovascular event | 1 participants |
| Placebo | Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks | Any cardiovascular event | 4 participants |
| Placebo | Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks | Any non-fatal cardiovascular event | 4 participants |
| Placebo | Number of Participants With Adjudicated Cardiovascular Events up to 26 Weeks | Any fatal cardiovascular event | 0 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events at 26 Weeks
A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 26 Weeks | 160 participants |
| 0.75 Milligram (mg) LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 26 Weeks | 156 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events at 26 Weeks | 162 participants |
Secondary
Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5%
Percentages of participants who achieved glycosylated hemoglobin (HbA1c) levels of \<7% or ≤6.5% were analyzed with Chi-squared test/Fisher's exact test.
Time frame: Baseline and 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo with evaluable glycosylated hemoglobin (HbA1c) data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Baseline | 6.8 percentage of participants |
| 1.5 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Baseline | 0.0 percentage of participants |
| 1.5 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Week 16 (n=216, n=234, n=225) | 66.7 percentage of participants |
| 1.5 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 16 (n=216, n=234, n=225) | 45.8 percentage of participants |
| 1.5 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Week 26 (n=206, n=226, n=210) | 62.1 percentage of participants |
| 1.5 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 26 (n=206, n=226, n=210) | 38.8 percentage of participants |
| 0.75 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 26 (n=206, n=226, n=210) | 35.8 percentage of participants |
| 0.75 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Baseline | 6.7 percentage of participants |
| 0.75 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 16 (n=216, n=234, n=225) | 36.8 percentage of participants |
| 0.75 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Week 26 (n=206, n=226, n=210) | 54.9 percentage of participants |
| 0.75 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Baseline | 0.4 percentage of participants |
| 0.75 Milligram (mg) LY2189265 | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Week 16 (n=216, n=234, n=225) | 59.0 percentage of participants |
| Placebo | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Baseline | 0.4 percentage of participants |
| Placebo | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Week 16 (n=216, n=234, n=225) | 12.9 percentage of participants |
| Placebo | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 26 (n=206, n=226, n=210) | 5.2 percentage of participants |
| Placebo | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels ≤6.5%, Week 16 (n=216, n=234, n=225) | 6.2 percentage of participants |
| Placebo | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Baseline | 8.0 percentage of participants |
| Placebo | Percentage of Participants Achieving an Glycosylated Hemoglobin (HbA1c) of <7% or ≤6.5% | HbA1c levels <7.0%, Week 26 (n=206, n=226, n=210) | 14.3 percentage of participants |
Secondary
Rate of Hypoglycemic Episodes
Hypoglycemic events (HE) were classified as severe (defined as an HE requiring assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as an HE with typical symptoms of hypoglycemia and a blood glucose level of ≤3.9 millimoles per liter \[mmol/L\]), asymptomatic (defined as an HE without typical symptoms of hypoglycemia but with a measured blood glucose of ≤3.9 mmol/L), nocturnal (defined as any HE occurring between bedtime and waking with a measured blood glucose of ≤3.9 mmol/L), or non-nocturnal. Hypoglycemia rate per 30 days was summarized at each visit by treatment group. The rate of hypoglycemia was analyzed using a generalized estimation equations model with a negative binomial distribution and a Logit link. Negative binomial mean was adjusted by treatment, visit, and visit by treatment interaction. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline, 16 and 26 weeks
Population: Participants who received at least one dose of LY2189265 or Placebo.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 Milligram (mg) LY2189265 | Rate of Hypoglycemic Episodes | Nocturnal | 0.06 events per participant per 30 days | Standard Deviation 0.3 |
| 1.5 Milligram (mg) LY2189265 | Rate of Hypoglycemic Episodes | Asymptomatic | 0.17 events per participant per 30 days | Standard Deviation 0.89 |
| 1.5 Milligram (mg) LY2189265 | Rate of Hypoglycemic Episodes | Severe | 0 events per participant per 30 days | Standard Deviation 0 |
| 1.5 Milligram (mg) LY2189265 | Rate of Hypoglycemic Episodes | Documented Symptomatic | 0.14 events per participant per 30 days | Standard Deviation 0.43 |
| 1.5 Milligram (mg) LY2189265 | Rate of Hypoglycemic Episodes | Non-nocturnal | 0.29 events per participant per 30 days | Standard Deviation 0.97 |
| 0.75 Milligram (mg) LY2189265 | Rate of Hypoglycemic Episodes | Asymptomatic | 0.15 events per participant per 30 days | Standard Deviation 0.59 |
| 0.75 Milligram (mg) LY2189265 | Rate of Hypoglycemic Episodes | Severe | 0 events per participant per 30 days | Standard Deviation 0 |
| 0.75 Milligram (mg) LY2189265 | Rate of Hypoglycemic Episodes | Documented Symptomatic | 0.16 events per participant per 30 days | Standard Deviation 0.59 |
| 0.75 Milligram (mg) LY2189265 | Rate of Hypoglycemic Episodes | Nocturnal | 0.12 events per participant per 30 days | Standard Deviation 0.64 |
| 0.75 Milligram (mg) LY2189265 | Rate of Hypoglycemic Episodes | Non-nocturnal | 0.26 events per participant per 30 days | Standard Deviation 0.7 |
| Placebo | Rate of Hypoglycemic Episodes | Non-nocturnal | 0.15 events per participant per 30 days | Standard Deviation 0.44 |
| Placebo | Rate of Hypoglycemic Episodes | Nocturnal | 0.03 events per participant per 30 days | Standard Deviation 0.22 |
| Placebo | Rate of Hypoglycemic Episodes | Severe | 0 events per participant per 30 days | Standard Deviation 0 |
| Placebo | Rate of Hypoglycemic Episodes | Asymptomatic | 0.06 events per participant per 30 days | Standard Deviation 0.25 |
| Placebo | Rate of Hypoglycemic Episodes | Documented Symptomatic | 0.08 events per participant per 30 days | Standard Deviation 0.39 |