Major Depressive Disorder
Conditions
Brief summary
The purpose of this study is to determine the effect of LY2216684 on heart rate of participants receiving Albuterol and Propranolol. Information about any side effects that may occur will also be collected.
Interventions
DRUGLY2216684
administered orally
DRUGalbuterol
administered orally
DRUGpropranolol
administered orally
DRUGplacebo for LY2216684
administered orally
DRUGplacebo for albuterol
administered orally
DRUGplacebo for propranolol
administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy, as determined by medical history and physical examination. * Male participants - Agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug. * Female participants - Are women of child-bearing potential who test negative for pregnancy at the time of enrollment, have used a reliable method of birth control for 6 weeks prior to administration of study drug, and agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug; or Women not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause \[at least 1 year without menses or 6 months without menses and a follicle stimulating hormone (FSH) \>40 milli-international units per milliliter (mIU/mL)\]. * Have a body weight \>50 kilograms (kg). * Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator. * Have venous access sufficient to allow blood sampling as per the protocol. * Have normal blood pressure and pulse rate (sitting position) as determined by the investigator. * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures. * Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site.
Exclusion criteria
* Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device other than the study drug, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. * Have known allergies to LY2216684, albuterol (Group 1 only), propranolol (Group 2 only), or related compounds. * Are persons who have previously completed or withdrawn from this study or any other study investigating LY2216684 within 6 months prior to screening. * Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study. * Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data. * Have a history of or current asthma, including exercise induced asthma. * Have a history or show evidence of significant active neuropsychiatric disease or have a history of suicide attempt or ideation. * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening. * Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies. * Show evidence of hepatitis C and/or positive hepatitis C antibody. * Show evidence of hepatitis B and/or positive hepatitis B surface antigen. * Are women with a positive pregnancy test or women who are lactating. * Intend to use over-the-counter or prescription medication (including hormonal contraceptives) within 14 days prior to dosing unless deemed acceptable by the investigator and Sponsor's medical monitor * Have donated blood of more than 500 milliliters (mL) within the last month. * Have an average weekly alcohol intake that exceeds 14 units per week, or are unwilling to stop alcohol consumption 48 hours prior to check-in in each period and while resident at the Clinical Research Unit (CRU) \[1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits\]. * Consume 5 or more cups of coffee (or other beverages of comparable caffeine content) per day, on a habitual basis, or any participants unwilling to adhere to study caffeine restrictions. * Have used any tobacco-containing or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to enrollment. * Have consumed grapefruit or grapefruit-containing products 7 days prior to enrollment and during the study. * Have a documented or suspected history of glaucoma. * Participants determined to be unsuitable by the investigator for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum, Minimum and Average Changes in Heart Rate | Period 1, 2, 3: Baseline, Days 1 and 3 and 5 (postdose every 10 minutes through 24 hours postdose) | Using a Holter monitor, heart rate was recorded every 10 minutes through 24 hours postdose on Days 1, 3, and 5 of each period. Baseline heart rate was the average of 10-minute readings taken over 2 hours prior to dosing on Day 1 of each period. Postdose heart rate was summarized over 1-hour increments using the average of the 10-minute readings within these intervals. The postdose heart rate for a day was the average heart rate for 24 hours. The least squares (LS) mean change from baseline heart rate is reported. LS mean was calculated using a mixed effects model and adjusted for participant, sequence, period, time, treatment, and time by treatment interaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum, Minimum and Average Changes in Systolic Blood Pressure | Period 1, 2, 3: Baseline, Days 1 and 3 and 5 (postdose every 15 minutes from 0600 hours through 2200 hours and every hour from 2200 hours through 0600 hours) | Systolic blood pressure was measured using ambulatory blood pressure monitoring (ABPM) recorded every 15 minutes during the daytime (0600 through 2200 hours) and every hour throughout the night time (2200 through 0600 hours) on Days 1, 3, and 5 of each period. Baseline systolic blood pressure was the average of 15-minute readings taken over 2 hours prior to dosing on Day 1 of each period. Postdose systolic blood pressure from ABPM was summarized over 1-hour increments using the average of the 15-minute readings within these intervals. The postdose systolic blood pressure for a day was the average systolic blood pressure for 24 hours. The least squares (LS) mean change from baseline systolic blood pressure is reported. LS mean was calculated using a mixed effects model and adjusted for participant, sequence, period, time, treatment, and time by treatment interaction. |
| Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Period 1, 2, 3: Baseline, Days 1 and 3 and 5 (postdose every 15 minutes from 0600 hours through 2200 hours and every hour from 2200 hours through 0600 hours) | Diastolic blood pressure was measured using ambulatory blood pressure monitoring (ABPM) recorded every 15 minutes during the daytime (0600 through 2200 hours) and every hour throughout the night time (2200 through 0600 hours) on Days 1, 3, and 5 of each period. Baseline diastolic blood pressure was the average of 15-minute readings taken over 2 hours prior to dosing on Day 1 of each period. Postdose diastolic blood pressure from ABPM was summarized over 1-hour increments using the average of the 15-minute readings within these intervals. The postdose diastolic blood pressure for a day was the average diastolic blood pressure for 24 hours. The least squares (LS) mean change from baseline diastolic blood pressure is reported. LS mean was calculated using a mixed effects model and adjusted for participant, sequence, period, time, treatment, and time by treatment interaction. |
Countries
United States
Participant flow
Pre-assignment details
This was a 3-period, crossover study conducted in 2 groups. Participants were randomized to 1 of 3 sequences in either the albuterol group (Group 1) or 1 of 3 sequences in the propranolol group (Group 2).
Participants by arm
| Arm | Count |
|---|---|
| Group 1, Any Sequence (LY2216684, Albuterol, or Placebo) Participants were administered LY2216684, albuterol, or placebo during Periods 1, 2, and 3.
LY2216684 or placebo was administered as an 18-milligram (mg) oral dose (two 9-mg tablets) once daily (QD) on Days 1 through 5 of each period.
Albuterol or placebo was co-administered as a 2-mg oral dose (one 2-mg tablet) QD on Days 1, 3, and 5 of each period. | 24 |
| Group 2, Any Sequence (LY2216684, Propranolol, or Placebo) Participants were administered LY2216684, propranolol, or placebo during Periods 1, 2, and 3.
LY2216684 or placebo was administered as an 18-milligram (mg) oral dose (two 9-mg tablets) QD on Days 1 through 5 of each period.
Propranolol or placebo was co-administered as a 40-mg oral dose (one 40-mg tablet) QD on Days 1, 3, and 5 of each period. | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| First Intervention (Period 1) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Third Intervention (Period 3) | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
| Washout Period 1 | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 |
| Washout Period 2 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 |
| Washout Period 2 | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Group 1, Any Sequence (LY2216684, Albuterol, or Placebo) | Group 2, Any Sequence (LY2216684, Propranolol, or Placebo) | Total |
|---|---|---|---|
| Age, Continuous | 35.5 years STANDARD_DEVIATION 12 | 36.3 years STANDARD_DEVIATION 10.9 | 35.9 years STANDARD_DEVIATION 11.4 |
| Body Mass Index (BMI) | 26.10 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 3.4 | 28.04 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 3.33 | 27.07 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 3.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 23 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 10 Participants | 16 Participants |
| Race/Ethnicity, Customized More than 1 race | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 16 Participants | 14 Participants | 30 Participants |
| Region of Enrollment United States | 24 Participants | 24 Participants | 48 Participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 17 Participants |
| Sex: Female, Male Male | 17 Participants | 14 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 24 | 2 / 24 | 13 / 24 | 9 / 22 | 8 / 22 | 13 / 22 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 22 | 0 / 22 | 0 / 22 |
Outcome results
Primary
Maximum, Minimum and Average Changes in Heart Rate
Using a Holter monitor, heart rate was recorded every 10 minutes through 24 hours postdose on Days 1, 3, and 5 of each period. Baseline heart rate was the average of 10-minute readings taken over 2 hours prior to dosing on Day 1 of each period. Postdose heart rate was summarized over 1-hour increments using the average of the 10-minute readings within these intervals. The postdose heart rate for a day was the average heart rate for 24 hours. The least squares (LS) mean change from baseline heart rate is reported. LS mean was calculated using a mixed effects model and adjusted for participant, sequence, period, time, treatment, and time by treatment interaction.
Time frame: Period 1, 2, 3: Baseline, Days 1 and 3 and 5 (postdose every 10 minutes through 24 hours postdose)
Population: Randomized participants with at least 1 postdose heart rate measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Minimum Change | -9.47 beats per minute (bpm) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Average Change | 14.6 beats per minute (bpm) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Average Change | 9.33 beats per minute (bpm) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Average Change | 12.6 beats per minute (bpm) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Maximum Change | 40.4 beats per minute (bpm) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Minimum Change | -7.05 beats per minute (bpm) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Minimum Change | -9.23 beats per minute (bpm) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Maximum Change | 33.4 beats per minute (bpm) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Maximum Change | 36.3 beats per minute (bpm) |
| Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Average Change | 1.05 beats per minute (bpm) |
| Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Average Change | 0.102 beats per minute (bpm) |
| Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Minimum Change | -15.2 beats per minute (bpm) |
| Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Average Change | -0.788 beats per minute (bpm) |
| Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Maximum Change | 15.7 beats per minute (bpm) |
| Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Minimum Change | -16.3 beats per minute (bpm) |
| Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Maximum Change | 19.7 beats per minute (bpm) |
| Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Maximum Change | 19.9 beats per minute (bpm) |
| Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Minimum Change | -16.3 beats per minute (bpm) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Minimum Change | -9.03 beats per minute (bpm) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Average Change | 14.3 beats per minute (bpm) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Maximum Change | 37.2 beats per minute (bpm) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Minimum Change | -7.27 beats per minute (bpm) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Average Change | 15.7 beats per minute (bpm) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Average Change | 10.9 beats per minute (bpm) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Maximum Change | 39.3 beats per minute (bpm) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Minimum Change | -9.76 beats per minute (bpm) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Maximum Change | 35.7 beats per minute (bpm) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Average Change | 14.2 beats per minute (bpm) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Maximum Change | 31.1 beats per minute (bpm) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Minimum Change | -5.81 beats per minute (bpm) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Average Change | 9.55 beats per minute (bpm) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Maximum Change | 37.2 beats per minute (bpm) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Minimum Change | -5.94 beats per minute (bpm) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Maximum Change | 36.9 beats per minute (bpm) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Minimum Change | -5.21 beats per minute (bpm) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Average Change | 15.0 beats per minute (bpm) |
| Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Minimum Change | -16.1 beats per minute (bpm) |
| Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Maximum Change | 15.2 beats per minute (bpm) |
| Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Maximum Change | 14.0 beats per minute (bpm) |
| Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Average Change | -3.94 beats per minute (bpm) |
| Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Average Change | -3.65 beats per minute (bpm) |
| Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Minimum Change | -15.4 beats per minute (bpm) |
| Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Minimum Change | -14.8 beats per minute (bpm) |
| Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Maximum Change | 9.41 beats per minute (bpm) |
| Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Average Change | -4.34 beats per minute (bpm) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Maximum Change | 17.2 beats per minute (bpm) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Maximum Change | 27.3 beats per minute (bpm) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Average Change | 6.01 beats per minute (bpm) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Average Change | 6.25 beats per minute (bpm) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Minimum Change | -9.46 beats per minute (bpm) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 5 Maximum Change | 26.3 beats per minute (bpm) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Average Change | 1.11 beats per minute (bpm) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 3 Minimum Change | -9.40 beats per minute (bpm) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Heart Rate | Day 1 Minimum Change | -10.4 beats per minute (bpm) |
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-3.96, 8.49]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-3.19, 3.59]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-2.25, 5.35]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [13.7, 26.2]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [2.8, 9.58]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [7.87, 15.5]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-18.9, -8.8]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-7.67, -1.56]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-11.5, -5.33]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [2.72, 12.9]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [1.3, 7.46]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [1.93, 8.18]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 3 where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-5.49, 7.3]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 3 where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-6.96, 1.54]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-2.85, 6.16]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 3 where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [11.2, 23.8]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [2.32, 10.7]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [9.75, 18.7]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-14.6, -5.34]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-7.22, 0.297]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-11.6, -4.71]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [7.39, 16.8]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [2.91, 10.5]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [6.88, 13.8]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-7.41, 5.3]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-2.15, 6.56]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-3.23, 5.47]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 5 where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [13.2, 25.6]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 5 where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [4.78, 13.3]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [10.4, 18.9]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-15.6, -5.52]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-9.26, 0.764]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-12.6, -4.87]
Comparison: Difference of LS means (test minus reference) for the maximum changes in heart rate on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [7.17, 17.4]
Comparison: Difference of LS means (test minus reference) for the minimum changes in heart rate on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [0.917, 11]
Comparison: Difference of LS means (test minus reference) for the average changes in heart rate on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [5.98, 13.8]
Secondary
Maximum, Minimum and Average Changes in Diastolic Blood Pressure
Diastolic blood pressure was measured using ambulatory blood pressure monitoring (ABPM) recorded every 15 minutes during the daytime (0600 through 2200 hours) and every hour throughout the night time (2200 through 0600 hours) on Days 1, 3, and 5 of each period. Baseline diastolic blood pressure was the average of 15-minute readings taken over 2 hours prior to dosing on Day 1 of each period. Postdose diastolic blood pressure from ABPM was summarized over 1-hour increments using the average of the 15-minute readings within these intervals. The postdose diastolic blood pressure for a day was the average diastolic blood pressure for 24 hours. The least squares (LS) mean change from baseline diastolic blood pressure is reported. LS mean was calculated using a mixed effects model and adjusted for participant, sequence, period, time, treatment, and time by treatment interaction.
Time frame: Period 1, 2, 3: Baseline, Days 1 and 3 and 5 (postdose every 15 minutes from 0600 hours through 2200 hours and every hour from 2200 hours through 0600 hours)
Population: Randomized participants with at least 1 postdose diastolic blood pressure measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Minimum Change | -17.3 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Average Change | -0.537 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Minimum Change | -17.0 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Minimum Change | -18.1 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Average Change | -0.674 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Maximum Change | 13.8 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Average | 0.233 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Maximum Change | 13.4 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Maximum Change | 13.6 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Minimum Change | -21.5 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Maximum Change | 12.8 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Average Change | -3.10 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Minimum Change | -21.6 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Minimum Change | -19.9 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Maximum Change | 10.8 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Average Change | -3.27 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Maximum Change | 11.8 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Average | -3.17 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Maximum Change | 12.2 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Average Change | -0.159 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Minimum Change | -20.5 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Maximum Change | 12.7 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Minimum Change | -18.6 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Maximum Change | 14.7 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Average | -0.140 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Average Change | -0.873 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Minimum Change | -16.2 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Maximum Change | 13.1 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Average | -0.631 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Minimum Change | -17.9 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Average Change | 0.481 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Maximum Change | 15.4 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Maximum Change | 14.9 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Minimum Change | -17.8 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Average Change | 0.619 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Minimum Change | -19.1 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Maximum Change | 8.16 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Minimum Change | -26.6 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Maximum Change | 6.87 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Minimum Change | -26.6 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Maximum Change | 6.58 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Average Change | -7.47 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Minimum Change | -26.7 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Average | -7.33 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Average Change | -7.80 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Average | -1.80 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Maximum Change | 10.6 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Minimum Change | -17.6 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 1 Average Change | -1.44 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Maximum Change | 12.5 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Minimum Change | -18.8 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 3 Average Change | -1.20 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Maximum Change | 13.8 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Diastolic Blood Pressure | Day 5 Minimum Change | -21.0 millimeters of mercury (mm Hg) |
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-3.9, 1.44]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-1.91, 4.02]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-2.58, 2.18]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-1.34, 4.07]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [0.674, 6.69]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-0.0178, 4.81]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-7.83, -0.619]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-4.45, 5.12]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-4.81, 0.969]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [-1.15, 6.1]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [4.3, 13.9]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [3.12, 8.94]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-4.65, 2.82]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-4.33, 3.44]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-2.2, 2.95]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-2.86, 4.62]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-0.966, 6.8]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [0.366, 5.52]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-6.84, 1.07]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-5.39, 3.44]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-5.3, 1.66]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [1.63, 9.56]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [3.39, 12.3]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [3.11, 10.1]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-3.23, 4.92]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-8.17, 1.21]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-2.88, 2.14]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-2.17, 5.98]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-3.62, 5.76]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [0.522, 5.55]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-3.9, 5.38]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-6.36, 2.47]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-4.79, 2.45]
Comparison: Difference of LS means (test minus reference) for the maximum changes in diastolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [2.59, 11.9]
Comparison: Difference of LS means (test minus reference) for the minimum changes in diastolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [1.13, 10]
Comparison: Difference of LS means (test minus reference) for the average changes in diastolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [1.89, 9.16]
Secondary
Maximum, Minimum and Average Changes in Systolic Blood Pressure
Systolic blood pressure was measured using ambulatory blood pressure monitoring (ABPM) recorded every 15 minutes during the daytime (0600 through 2200 hours) and every hour throughout the night time (2200 through 0600 hours) on Days 1, 3, and 5 of each period. Baseline systolic blood pressure was the average of 15-minute readings taken over 2 hours prior to dosing on Day 1 of each period. Postdose systolic blood pressure from ABPM was summarized over 1-hour increments using the average of the 15-minute readings within these intervals. The postdose systolic blood pressure for a day was the average systolic blood pressure for 24 hours. The least squares (LS) mean change from baseline systolic blood pressure is reported. LS mean was calculated using a mixed effects model and adjusted for participant, sequence, period, time, treatment, and time by treatment interaction.
Time frame: Period 1, 2, 3: Baseline, Days 1 and 3 and 5 (postdose every 15 minutes from 0600 hours through 2200 hours and every hour from 2200 hours through 0600 hours)
Population: Randomized participants with at least 1 postdose systolic blood pressure measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Minimum Change | -18.0 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Average Change | -1.65 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Minimum Change | -20.8 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Maximum Change | 13.5 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Average Change | -0.986 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Minimum Change | -19.4 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Average Change | -2.07 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Maximum Change | 14.1 millimeters of mercury (mm Hg) |
| LY2216684 (Group 1) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Maximum Change | 13.9 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Minimum Change | -24.9 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Maximum Change | 15.9 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Minimum Change | -22.1 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Average Change | -1.87 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Minimum Change | -20.5 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Maximum Change | 15.2 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Average Change | -0.912 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Maximum Change | 15.6 millimeters of mercury (mm Hg) |
| Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Average Change | -2.36 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Maximum Change | 15.8 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Average Change | -1.99 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Minimum Change | -18.9 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Maximum Change | 13.5 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Minimum Change | -20.6 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Maximum Change | 16.2 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Average Change | -0.233 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Average Change | 1.69 millimeters of mercury (mm Hg) |
| LY2216684+Albuterol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Minimum Change | -15.3 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Maximum Change | 14.7 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Average Change | -1.72 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Minimum Change | -17.7 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Average Change | 1.73 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Maximum Change | 15.3 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Maximum Change | 17.3 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Minimum Change | -18.5 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Average Change | 0.289 millimeters of mercury (mm Hg) |
| LY2216684 (Group 2) | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Minimum Change | -21.1 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Maximum Change | 9.39 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Minimum Change | -27.2 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Maximum Change | 7.99 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Minimum Change | -24.9 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Maximum Change | 11.1 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Average Change | -8.50 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Minimum Change | -29.0 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Average Change | -6.83 millimeters of mercury (mm Hg) |
| Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Average Change | -8.75 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Average Change | -2.55 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Maximum Change | 10.9 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Minimum Change | -17.5 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 1 Average Change | -1.35 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Maximum Change | 11.2 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Minimum Change | -23.3 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 3 Average Change | -3.91 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Maximum Change | 13.1 millimeters of mercury (mm Hg) |
| LY2216684+Propranolol | Maximum, Minimum and Average Changes in Systolic Blood Pressure | Day 5 Minimum Change | -21.2 millimeters of mercury (mm Hg) |
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-1.81, 5.06]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-1.38, 6.85]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-0.209, 5.56]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-2.94, 4.02]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [1.09, 9.43]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 1, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-0.322, 5.52]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-11.5, -1.41]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-5.21, 5.56]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-6.73, 0.557]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [-3.61, 6.53]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [5.99, 16.8]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 1, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [3.49, 10.8]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-5.28, 5.34]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-5.93, 3.59]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-4.35, 3.68]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-7.42, 3.2]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-0.404, 9.12]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 3, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-4.14, 3.9]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-9.69, 1.37]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-10.2, 0.718]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-8.71, 0.32]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [-2.34, 8.74]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [-1.54, 9.43]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 3, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [0.319, 9.37]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-3.44, 8.12]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-3.22, 7]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the LY2216684 (Group 1) treatment arm.95% CI: [-1.85, 5.52]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-5.45, 6.1]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-1.93, 8.29]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 5, where test is the LY2216684+albuterol treatment arm and reference is the albuterol treatment arm.95% CI: [-1.56, 5.81]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-6.79, 3.59]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-5, 4.68]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the LY2216684 (Group 2) treatment arm.95% CI: [-5.2, 3.54]
Comparison: Difference of LS means (test minus reference) for the maximum changes in systolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [-3.27, 7.17]
Comparison: Difference of LS means (test minus reference) for the minimum changes in systolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [-1.17, 8.59]
Comparison: Difference of LS means (test minus reference) for the average changes in systolic blood pressure on Day 5, where test is the LY2216684+propranolol treatment arm and reference is the propranolol treatment arm.95% CI: [-0.103, 8.67]