Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of LY2216684 in Healthy Participants Receiving Albuterol or Propanolol

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01263197
Recruitment Status : Completed
First Posted : December 20, 2010
Results First Posted : October 22, 2018
Last Update Posted : January 29, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: LY2216684
Drug: albuterol
Drug: propranolol
Drug: placebo for LY2216684
Drug: placebo for albuterol
Drug: placebo for propranolol
Enrollment 48
Recruitment Details  
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).
Arm/Group Title Group 1, Seq 1: LY2216684, Albuterol, LY2216684+Albuterol Group 1, Seq 2: Albuterol, LY2216684+Albuterol, LY2216684 Group 1, Seq 3: LY2216684+Albuterol, LY2216684, Albuterol Group 2, Seq 1: LY2216684, Propranolol, LY2216684+Propranolol Group 2, Seq 2: Propranolol, LY2216684+Propranolol, LY2216684 Group 2, Seq 3: LY2216684+Propranolol, LY2216684, Propranolol
Hide Arm/Group Description

Group 1, Sequence (Seq) 1

First intervention: LY2216684 administered as an 18-milligram (mg) oral dose (two 9-mg tablets) once daily (QD) on Days 1 through 5 with single oral doses of placebo (for albuterol) co-administered on Days 1, 3, and 5.

Second intervention: Oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5.

Third intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5.

There was a minimum 7-day washout between each intervention period.

Group 1, Sequence 2

First intervention: Oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5.

Second intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5.

Third intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of placebo (for albuterol) co-administered on Days 1, 3, and 5.

There was a minimum 7-day washout between each intervention period.

Group 1, Sequence 3

First intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5.

Second intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of placebo (for albuterol) co-administered on Days 1, 3, and 5.

Third intervention: Oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5.

There was a minimum 7-day washout between each intervention period.

Group 2, Sequence 1

First intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of placebo (for propranolol) co-administered on Days 1, 3, and 5.

Second intervention: Oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5.

Third intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5.

There was a minimum 7-day washout between each intervention period.

Group 2, Sequence 2

First intervention: Oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5.

Second intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5.

Third intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of placebo (for propranolol) co-administered on Days 1, 3, and 5.

There was a minimum 7-day washout between each intervention period.

Group 2, Sequence 3

First intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5.

Second intervention: LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of placebo (for propranolol) co-administered on Days 1, 3, and 5.

Third intervention: Oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5.

There was a minimum 7-day washout between each intervention period.

Period Title: First Intervention (Period 1)
Started 8 8 8 8 8 8
Completed 8 8 8 8 8 7
Not Completed 0 0 0 0 0 1
Reason Not Completed
Adverse Event             0             0             0             0             0             1
Period Title: Washout Period 1
Started 8 8 8 8 8 7
Completed 8 8 8 8 7 7
Not Completed 0 0 0 0 1 0
Reason Not Completed
Protocol Violation             0             0             0             0             1             0
Period Title: Second Intervention (Period 2)
Started 8 8 8 8 7 7
Completed 8 8 8 8 7 7
Not Completed 0 0 0 0 0 0
Period Title: Washout Period 2
Started 8 8 8 8 7 7
Completed 8 8 8 7 7 6
Not Completed 0 0 0 1 0 1
Reason Not Completed
Physician Decision             0             0             0             0             0             1
Protocol Violation             0             0             0             1             0             0
Period Title: Third Intervention (Period 3)
Started 8 8 8 7 7 6
Completed 8 7 8 7 7 6
Not Completed 0 1 0 0 0 0
Reason Not Completed
Adverse Event             0             1             0             0             0             0
Arm/Group Title Group 1, Any Sequence (LY2216684, Albuterol, or Placebo) Group 2, Any Sequence (LY2216684, Propranolol, or Placebo) Total
Hide Arm/Group Description

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 24 24 48
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 24 participants 48 participants
35.5  (12.0) 36.3  (10.9) 35.9  (11.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 48 participants
Female
7
  29.2%
10
  41.7%
17
  35.4%
Male
17
  70.8%
14
  58.3%
31
  64.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 48 participants
Hispanic or Latino
2
   8.3%
1
   4.2%
3
   6.3%
Not Hispanic or Latino
22
  91.7%
23
  95.8%
45
  93.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 48 participants
Black or African American
6
  25.0%
10
  41.7%
16
  33.3%
White
16
  66.7%
14
  58.3%
30
  62.5%
More than 1 race
2
   8.3%
0
   0.0%
2
   4.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 24 participants 24 participants 48 participants
24
 100.0%
24
 100.0%
48
 100.0%
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms per square meter (kg/m^2)
Number Analyzed 24 participants 24 participants 48 participants
26.10  (3.40) 28.04  (3.33) 27.07  (3.47)
[1]
Measure Description: BMI is an estimate of body fat based on body weight divided by height squared.
1.Primary Outcome
Title Maximum, Minimum and Average Changes in Heart Rate
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with at least 1 postdose heart rate measurement.
Arm/Group Title LY2216684 (Group 1) Albuterol LY2216684+Albuterol LY2216684 (Group 2) Propranolol LY2216684+Propranolol
Hide Arm/Group Description:
Participants randomized to Group 1 who received LY2216684 administered as an 18-milligram (mg) oral dose (two 9-mg tablets) once daily (QD) on Days 1 through 5 with single oral doses of placebo (for albuterol) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 1 who received oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 1 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 2 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of placebo (for propranolol) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 2 who received oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 2 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Overall Number of Participants Analyzed 24 24 24 22 22 22
Least Squares Mean (90% Confidence Interval)
Unit of Measure: beats per minute (bpm)
Day 1 Maximum Change
33.4
(29.6 to 37.2)
15.7
(11.9 to 19.5)
35.7
(31.9 to 39.5)
31.1
(28.1 to 34.1)
9.41
(6.40 to 12.4)
17.2
(14.2 to 20.2)
Day 1 Minimum Change
-9.23
(-11.4 to -7.05)
-15.2
(-17.4 to -13.0)
-9.03
(-11.2 to -6.86)
-5.81
(-7.97 to -3.65)
-14.8
(-17.0 to -12.6)
-10.4
(-12.6 to -8.27)
Day 1 Average Change
9.33
(7.08 to 11.6)
-0.788
(-3.03 to 1.46)
10.9
(8.64 to 13.1)
9.55
(7.50 to 11.6)
-3.94
(-6.00 to -1.89)
1.11
(-0.934 to 3.16)
Day 3 Maximum Change
36.3
(32.1 to 40.4)
19.7
(15.6 to 23.7)
37.2
(33.0 to 41.3)
37.2
(34.0 to 40.5)
15.2
(12.0 to 18.4)
27.3
(24.1 to 30.5)
Day 3 Minimum Change
-7.05
(-9.95 to -4.15)
-16.3
(-19.1 to -13.4)
-9.76
(-12.7 to -6.86)
-5.94
(-8.45 to -3.42)
-16.1
(-18.6 to -13.6)
-9.40
(-11.9 to -6.89)
Day 3 Average Change
12.6
(9.82 to 15.5)
0.102
(-2.66 to 2.87)
14.3
(11.5 to 17.1)
14.2
(11.9 to 16.5)
-4.34
(-6.65 to -2.03)
6.01
(3.71 to 8.31)
Day 5 Maximum Change
40.4
(35.8 to 45.0)
19.9
(15.5 to 24.3)
39.3
(34.9 to 43.8)
36.9
(33.5 to 40.3)
14.0
(10.6 to 17.4)
26.3
(22.9 to 29.7)
Day 5 Minimum Change
-9.47
(-12.1 to -6.81)
-16.3
(-18.9 to -13.8)
-7.27
(-9.88 to -4.66)
-5.21
(-8.19 to -2.23)
-15.4
(-18.4 to -12.4)
-9.46
(-12.4 to -6.48)
Day 5 Average Change
14.6
(11.6 to 17.5)
1.05
(-1.79 to 3.89)
15.7
(12.8 to 18.6)
15.0
(12.4 to 17.6)
-3.65
(-6.27 to -1.03)
6.25
(3.64 to 8.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.27
Confidence Interval (2-Sided) 95%
-3.96 to 8.49
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.198
Confidence Interval (2-Sided) 95%
-3.19 to 3.59
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
-2.25 to 5.35
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 20.0
Confidence Interval (2-Sided) 95%
13.7 to 26.2
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 6.19
Confidence Interval (2-Sided) 95%
2.80 to 9.58
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 11.7
Confidence Interval (2-Sided) 95%
7.87 to 15.5
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -13.9
Confidence Interval (2-Sided) 95%
-18.9 to -8.80
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.62
Confidence Interval (2-Sided) 95%
-7.67 to -1.56
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -8.43
Confidence Interval (2-Sided) 95%
-11.5 to -5.33
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 7.80
Confidence Interval (2-Sided) 95%
2.72 to 12.9
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.38
Confidence Interval (2-Sided) 95%
1.30 to 7.46
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 5.06
Confidence Interval (2-Sided) 95%
1.93 to 8.18
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.905
Confidence Interval (2-Sided) 95%
-5.49 to 7.30
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -2.71
Confidence Interval (2-Sided) 95%
-6.96 to 1.54
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.66
Confidence Interval (2-Sided) 95%
-2.85 to 6.16
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 17.5
Confidence Interval (2-Sided) 95%
11.2 to 23.8
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 6.51
Confidence Interval (2-Sided) 95%
2.32 to 10.7
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 14.2
Confidence Interval (2-Sided) 95%
9.75 to 18.7
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -9.98
Confidence Interval (2-Sided) 95%
-14.6 to -5.34
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -3.46
Confidence Interval (2-Sided) 95%
-7.22 to 0.297
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -8.16
Confidence Interval (2-Sided) 95%
-11.6 to -4.71
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 12.1
Confidence Interval (2-Sided) 95%
7.39 to 16.8
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 6.70
Confidence Interval (2-Sided) 95%
2.91 to 10.5
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 10.3
Confidence Interval (2-Sided) 95%
6.88 to 13.8
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.06
Confidence Interval (2-Sided) 95%
-7.41 to 5.30
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.20
Confidence Interval (2-Sided) 95%
-2.15 to 6.56
Estimation Comments [Not Specified]
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
-3.23 to 5.47
Estimation Comments [Not Specified]
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 19.4
Confidence Interval (2-Sided) 95%
13.2 to 25.6
Estimation Comments [Not Specified]
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 9.04
Confidence Interval (2-Sided) 95%
4.78 to 13.3
Estimation Comments [Not Specified]
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 14.7
Confidence Interval (2-Sided) 95%
10.4 to 18.9
Estimation Comments [Not Specified]
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -10.6
Confidence Interval (2-Sided) 95%
-15.6 to -5.52
Estimation Comments [Not Specified]
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.25
Confidence Interval (2-Sided) 95%
-9.26 to 0.764
Estimation Comments [Not Specified]
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -8.76
Confidence Interval (2-Sided) 95%
-12.6 to -4.87
Estimation Comments [Not Specified]
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 12.3
Confidence Interval (2-Sided) 95%
7.17 to 17.4
Estimation Comments [Not Specified]
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 5.95
Confidence Interval (2-Sided) 95%
0.917 to 11.0
Estimation Comments [Not Specified]
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 9.90
Confidence Interval (2-Sided) 95%
5.98 to 13.8
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Maximum, Minimum and Average Changes in Systolic Blood Pressure
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with at least 1 postdose systolic blood pressure measurement.
Arm/Group Title LY2216684 (Group 1) Albuterol LY2216684+Albuterol LY2216684 (Group 2) Propranolol LY2216684+Propranolol
Hide Arm/Group Description:
Participants randomized to Group 1 who received LY2216684 administered as an 18-milligram (mg) oral dose (two 9-mg tablets) once daily (QD) on Days 1 through 5 with single oral doses of placebo (for albuterol) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 1 who received oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 1 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 2 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of placebo (for propranolol) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 2 who received oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 2 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Overall Number of Participants Analyzed 24 23 24 22 22 22
Least Squares Mean (90% Confidence Interval)
Unit of Measure: millimeters of mercury (mm Hg)
Day 1 Maximum Change
14.1
(11.9 to 16.4)
15.2
(12.9 to 17.5)
15.8
(13.5 to 18.0)
17.3
(14.3 to 20.3)
9.39
(6.39 to 12.4)
10.9
(7.87 to 13.8)
Day 1 Minimum Change
-18.0
(-20.8 to -15.2)
-20.5
(-23.4 to -17.7)
-15.3
(-18.1 to -12.5)
-17.7
(-21.3 to -14.2)
-29.0
(-32.5 to -25.4)
-17.5
(-21.1 to -14.0)
Day 1 Average Change
-0.986
(-2.97 to 0.995)
-0.912
(-2.93 to 1.11)
1.69
(-0.292 to 3.67)
1.73
(-0.508 to 3.97)
-8.50
(-10.7 to -6.25)
-1.35
(-3.59 to 0.884)
Day 3 Maximum Change
13.5
(9.99 to 16.9)
15.6
(12.1 to 19.1)
13.5
(10.1 to 16.9)
15.3
(12.1 to 18.6)
7.99
(4.74 to 11.2)
11.2
(7.89 to 14.5)
Day 3 Minimum Change
-19.4
(-22.3 to -16.5)
-24.9
(-27.8 to -22.0)
-20.6
(-23.4 to -17.7)
-18.5
(-21.7 to -15.3)
-27.2
(-30.4 to -24.0)
-23.3
(-26.5 to -20.0)
Day 3 Average Change
-1.65
(-4.07 to 0.762)
-1.87
(-4.29 to 0.548)
-1.99
(-4.35 to 0.375)
0.289
(-2.35 to 2.93)
-8.75
(-11.4 to -6.10)
-3.91
(-6.60 to -1.21)
Day 5 Maximum Change
13.9
(10.4 to 17.3)
15.9
(12.5 to 19.4)
16.2
(12.9 to 19.6)
14.7
(11.3 to 18.0)
11.1
(7.72 to 14.5)
13.1
(9.69 to 16.4)
Day 5 Minimum Change
-20.8
(-24.0 to -17.6)
-22.1
(-25.3 to -18.9)
-18.9
(-22.0 to -15.8)
-21.1
(-24.5 to -17.6)
-24.9
(-28.3 to -21.5)
-21.2
(-24.6 to -17.8)
Day 5 Average Change
-2.07
(-4.40 to 0.270)
-2.36
(-4.69 to -0.0204)
-0.233
(-2.52 to 2.05)
-1.72
(-4.30 to 0.865)
-6.83
(-9.42 to -4.24)
-2.55
(-5.13 to 0.0363)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.62
Confidence Interval (2-Sided) 95%
-1.81 to 5.06
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.73
Confidence Interval (2-Sided) 95%
-1.38 to 6.85
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.67
Confidence Interval (2-Sided) 95%
-0.209 to 5.56
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.541
Confidence Interval (2-Sided) 95%
-2.94 to 4.02
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 5.26
Confidence Interval (2-Sided) 95%
1.09 to 9.43
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.60
Confidence Interval (2-Sided) 95%
-0.322 to 5.52
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -6.46
Confidence Interval (2-Sided) 95%
-11.5 to -1.41
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.171
Confidence Interval (2-Sided) 95%
-5.21 to 5.56
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -3.09
Confidence Interval (2-Sided) 95%
-6.73 to 0.557
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
-3.61 to 6.53
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 11.4
Confidence Interval (2-Sided) 95%
5.99 to 16.8
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 7.15
Confidence Interval (2-Sided) 95%
3.49 to 10.8
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.0309
Confidence Interval (2-Sided) 95%
-5.28 to 5.34
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.17
Confidence Interval (2-Sided) 95%
-5.93 to 3.59
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.333
Confidence Interval (2-Sided) 95%
-4.35 to 3.68
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -2.11
Confidence Interval (2-Sided) 95%
-7.42 to 3.20
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.36
Confidence Interval (2-Sided) 95%
-0.404 to 9.12
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.119
Confidence Interval (2-Sided) 95%
-4.14 to 3.90
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.16
Confidence Interval (2-Sided) 95%
-9.69 to 1.37
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.76
Confidence Interval (2-Sided) 95%
-10.2 to 0.718
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.20
Confidence Interval (2-Sided) 95%
-8.71 to 0.320
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 3.20
Confidence Interval (2-Sided) 95%
-2.34 to 8.74
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 3.95
Confidence Interval (2-Sided) 95%
-1.54 to 9.43
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.84
Confidence Interval (2-Sided) 95%
0.319 to 9.37
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.34
Confidence Interval (2-Sided) 95%
-3.44 to 8.12
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.89
Confidence Interval (2-Sided) 95%
-3.22 to 7.00
Estimation Comments [Not Specified]
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.83
Confidence Interval (2-Sided) 95%
-1.85 to 5.52
Estimation Comments [Not Specified]
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.327
Confidence Interval (2-Sided) 95%
-5.45 to 6.10
Estimation Comments [Not Specified]
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 3.18
Confidence Interval (2-Sided) 95%
-1.93 to 8.29
Estimation Comments [Not Specified]
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.12
Confidence Interval (2-Sided) 95%
-1.56 to 5.81
Estimation Comments [Not Specified]
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.60
Confidence Interval (2-Sided) 95%
-6.79 to 3.59
Estimation Comments [Not Specified]
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.163
Confidence Interval (2-Sided) 95%
-5.00 to 4.68
Estimation Comments [Not Specified]
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.829
Confidence Interval (2-Sided) 95%
-5.20 to 3.54
Estimation Comments [Not Specified]
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.95
Confidence Interval (2-Sided) 95%
-3.27 to 7.17
Estimation Comments [Not Specified]
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 3.71
Confidence Interval (2-Sided) 95%
-1.17 to 8.59
Estimation Comments [Not Specified]
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 4.28
Confidence Interval (2-Sided) 95%
-0.103 to 8.67
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Maximum, Minimum and Average Changes in Diastolic Blood Pressure
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with at least 1 postdose diastolic blood pressure measurement.
Arm/Group Title LY2216684 (Group 1) Albuterol LY2216684+Albuterol LY2216684 (Group 2) Propranolol LY2216684+Propranolol
Hide Arm/Group Description:
Participants randomized to Group 1 who received LY2216684 administered as an 18-milligram (mg) oral dose (two 9-mg tablets) once daily (QD) on Days 1 through 5 with single oral doses of placebo (for albuterol) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 1 who received oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 1 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 2 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of placebo (for propranolol) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 2 who received oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Participants randomized to Group 2 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
Overall Number of Participants Analyzed 24 23 24 22 22 22
Least Squares Mean (90% Confidence Interval)
Unit of Measure: millimeters of mercury (mm Hg)
Day 1 Maximum Change
13.4
(11.7 to 15.2)
10.8
(9.05 to 12.6)
12.2
(10.5 to 13.9)
14.9
(12.6 to 17.1)
8.16
(5.88 to 10.4)
10.6
(8.37 to 12.9)
Day 1 Minimum Change
-17.3
(-19.4 to -15.1)
-19.9
(-22.1 to -17.7)
-16.2
(-18.4 to -14.1)
-17.9
(-21.2 to -14.6)
-26.7
(-30.0 to -23.4)
-17.6
(-20.9 to -14.3)
Day 1 Average Change
-0.674
(-2.38 to 1.03)
-3.27
(-5.01 to -1.53)
-0.873
(-2.58 to 0.833)
0.481
(-1.37 to 2.33)
-7.47
(-9.33 to -5.61)
-1.44
(-3.29 to 0.410)
Day 3 Maximum Change
13.6
(11.4 to 15.9)
11.8
(9.60 to 14.1)
12.7
(10.5 to 14.9)
15.4
(13.0 to 17.7)
6.87
(4.51 to 9.24)
12.5
(10.1 to 14.9)
Day 3 Minimum Change
-18.1
(-21.0 to -15.3)
-21.5
(-24.3 to -18.7)
-18.6
(-21.4 to -15.8)
-17.8
(-20.5 to -15.2)
-26.6
(-29.3 to -24.0)
-18.8
(-21.5 to -16.1)
Day 3 Average Change
-0.537
(-2.24 to 1.17)
-3.10
(-4.80 to -1.40)
-0.159
(-1.83 to 1.51)
0.619
(-1.44 to 2.68)
-7.80
(-9.87 to -5.74)
-1.20
(-3.31 to 0.900)
Day 5 Maximum Change
13.8
(11.3 to 16.4)
12.8
(10.2 to 15.3)
14.7
(12.2 to 17.2)
13.1
(10.2 to 16.0)
6.58
(3.69 to 9.47)
13.8
(11.0 to 16.7)
Day 5 Minimum Change
-17.0
(-20.2 to -13.8)
-21.6
(-24.8 to -18.4)
-20.5
(-23.7 to -17.3)
-19.1
(-22.2 to -15.9)
-26.6
(-29.7 to -23.4)
-21.0
(-24.2 to -17.8)
Day 5 Average
0.233
(-1.74 to 2.20)
-3.17
(-5.14 to -1.20)
-0.140
(-2.08 to 1.80)
-0.631
(-2.81 to 1.55)
-7.33
(-9.52 to -5.14)
-1.80
(-3.99 to 0.381)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.23
Confidence Interval (2-Sided) 95%
-3.90 to 1.44
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
-1.91 to 4.02
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.199
Confidence Interval (2-Sided) 95%
-2.58 to 2.18
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.37
Confidence Interval (2-Sided) 95%
-1.34 to 4.07
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 3.68
Confidence Interval (2-Sided) 95%
0.674 to 6.69
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.40
Confidence Interval (2-Sided) 95%
-0.0178 to 4.81
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -4.22
Confidence Interval (2-Sided) 95%
-7.83 to -0.619
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.335
Confidence Interval (2-Sided) 95%
-4.45 to 5.12
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.92
Confidence Interval (2-Sided) 95%
-4.81 to 0.969
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.47
Confidence Interval (2-Sided) 95%
-1.15 to 6.10
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 9.12
Confidence Interval (2-Sided) 95%
4.30 to 13.9
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 6.03
Confidence Interval (2-Sided) 95%
3.12 to 8.94
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.913
Confidence Interval (2-Sided) 95%
-4.65 to 2.82
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.444
Confidence Interval (2-Sided) 95%
-4.33 to 3.44
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.378
Confidence Interval (2-Sided) 95%
-2.20 to 2.95
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.878
Confidence Interval (2-Sided) 95%
-2.86 to 4.62
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.92
Confidence Interval (2-Sided) 95%
-0.966 to 6.80
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.94
Confidence Interval (2-Sided) 95%
0.366 to 5.52
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -2.88
Confidence Interval (2-Sided) 95%
-6.84 to 1.07
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.975
Confidence Interval (2-Sided) 95%
-5.39 to 3.44
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.82
Confidence Interval (2-Sided) 95%
-5.30 to 1.66
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 5.60
Confidence Interval (2-Sided) 95%
1.63 to 9.56
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 7.82
Confidence Interval (2-Sided) 95%
3.39 to 12.3
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 6.60
Confidence Interval (2-Sided) 95%
3.11 to 10.1
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.847
Confidence Interval (2-Sided) 95%
-3.23 to 4.92
Estimation Comments [Not Specified]
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -3.48
Confidence Interval (2-Sided) 95%
-8.17 to 1.21
Estimation Comments [Not Specified]
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 1), LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.372
Confidence Interval (2-Sided) 95%
-2.88 to 2.14
Estimation Comments [Not Specified]
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.90
Confidence Interval (2-Sided) 95%
-2.17 to 5.98
Estimation Comments [Not Specified]
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
-3.62 to 5.76
Estimation Comments [Not Specified]
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Albuterol, LY2216684+Albuterol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 3.03
Confidence Interval (2-Sided) 95%
0.522 to 5.55
Estimation Comments [Not Specified]
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.737
Confidence Interval (2-Sided) 95%
-3.90 to 5.38
Estimation Comments [Not Specified]
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.95
Confidence Interval (2-Sided) 95%
-6.36 to 2.47
Estimation Comments [Not Specified]
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection LY2216684 (Group 2), LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -1.17
Confidence Interval (2-Sided) 95%
-4.79 to 2.45
Estimation Comments [Not Specified]
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 7.25
Confidence Interval (2-Sided) 95%
2.59 to 11.9
Estimation Comments [Not Specified]
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 5.58
Confidence Interval (2-Sided) 95%
1.13 to 10.0
Estimation Comments [Not Specified]
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Propranolol, LY2216684+Propranolol
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 5.53
Confidence Interval (2-Sided) 95%
1.89 to 9.16
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LY2216684 (Group 1) Albuterol LY2216684+Albuterol LY2216684 (Group 2) Propranolol LY2216684+Propranolol
Hide Arm/Group Description Participants randomized to Group 1 who received LY2216684 administered as an 18-milligram (mg) oral dose (two 9-mg tablets) once daily (QD) on Days 1 through 5 with single oral doses of placebo (for albuterol) co-administered on Days 1, 3, and 5 in any treatment period. Participants randomized to Group 1 who received who received oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period. Participants randomized to Group 1 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 2 mg albuterol (one 2-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period. Participants randomized to Group 2 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of placebo (for propranolol) co-administered on Days 1, 3, and 5 in any treatment period. Participants randomized to Group 2 who received oral doses of placebo (for LY2216684) administered QD on Days 1 through 5 with single oral doses of 40-mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period. Participants randomized to Group 2 who received LY2216684 administered as an 18-mg oral dose (two 9-mg tablets) QD on Days 1 through 5 with single oral doses of 40 mg propranolol (one 40-mg tablet) co-administered on Days 1, 3, and 5 in any treatment period.
All-Cause Mortality
LY2216684 (Group 1) Albuterol LY2216684+Albuterol LY2216684 (Group 2) Propranolol LY2216684+Propranolol
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
LY2216684 (Group 1) Albuterol LY2216684+Albuterol LY2216684 (Group 2) Propranolol LY2216684+Propranolol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/24 (0.00%)      0/24 (0.00%)      0/24 (0.00%)      0/22 (0.00%)      0/22 (0.00%)      0/22 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
LY2216684 (Group 1) Albuterol LY2216684+Albuterol LY2216684 (Group 2) Propranolol LY2216684+Propranolol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/24 (54.17%)      2/24 (8.33%)      13/24 (54.17%)      9/22 (40.91%)      8/22 (36.36%)      13/22 (59.09%)    
Cardiac disorders             
Palpitations  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Tachycardia  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Ventricular tachycardia  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1
Eye disorders             
Lacrimation increased  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Gastrointestinal disorders             
Abdominal pain  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0
Chapped lips  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0
Constipation  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 1/22 (4.55%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0
Dry mouth  1  1/24 (4.17%)  1 0/24 (0.00%)  0 2/24 (8.33%)  2 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Nausea  1  5/24 (20.83%)  5 0/24 (0.00%)  0 3/24 (12.50%)  3 3/22 (13.64%)  3 0/22 (0.00%)  0 2/22 (9.09%)  2
Vomiting  1  2/24 (8.33%)  2 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
General disorders             
Application site irritation  1  3/24 (12.50%)  3 1/24 (4.17%)  1 1/24 (4.17%)  1 1/22 (4.55%)  1 0/22 (0.00%)  0 3/22 (13.64%)  3
Chest pain  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Chills  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 2/22 (9.09%)  2 0/22 (0.00%)  0 1/22 (4.55%)  1
Fatigue  1  0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Feeling hot  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0 1/22 (4.55%)  1
Irritability  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0
Vessel puncture site pain  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0
Infections and infestations             
Bronchitis  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0
Carbuncle  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1
Influenza  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1
Subcutaneous abscess  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Upper respiratory tract infection  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1 1/22 (4.55%)  1
Injury, poisoning and procedural complications             
Excoriation  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Groin pain  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Nervous system disorders             
Dizziness  1  3/24 (12.50%)  3 0/24 (0.00%)  0 2/24 (8.33%)  2 0/22 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  2
Headache  1  3/24 (12.50%)  3 1/24 (4.17%)  2 4/24 (16.67%)  4 0/22 (0.00%)  0 3/22 (13.64%)  3 2/22 (9.09%)  2
Memory impairment  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1
Paraesthesia  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1
Presyncope  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 2/22 (9.09%)  2 0/22 (0.00%)  0
Somnolence  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 1/22 (4.55%)  1 0/22 (0.00%)  0 1/22 (4.55%)  1
Tremor  1  1/24 (4.17%)  1 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Psychiatric disorders             
Agitation  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Anxiety  1  0/24 (0.00%)  0 0/24 (0.00%)  0 2/24 (8.33%)  2 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Depression  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0
Insomnia  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0
Renal and urinary disorders             
Urinary hesitation  1  0/24 (0.00%)  0 0/24 (0.00%)  0 2/24 (8.33%)  2 1/22 (4.55%)  1 0/22 (0.00%)  0 2/22 (9.09%)  2
Reproductive system and breast disorders             
Dysmenorrhoea  1  0/7 (0.00%)  0 0/7 (0.00%)  0 0/7 (0.00%)  0 0/10 (0.00%)  0 1/10 (10.00%)  1 0/9 (0.00%)  0
Genital pain  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Penile discharge  1  0/17 (0.00%)  0 0/17 (0.00%)  0 0/17 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 0/13 (0.00%)  0
Penile size reduced  1  0/17 (0.00%)  0 0/17 (0.00%)  0 1/17 (5.88%)  1 0/12 (0.00%)  0 0/12 (0.00%)  0 1/13 (7.69%)  1
Scrotal pain  1  1/17 (5.88%)  1 0/17 (0.00%)  0 0/17 (0.00%)  0 0/12 (0.00%)  0 0/12 (0.00%)  0 0/13 (0.00%)  0
Testicular pain  1  0/17 (0.00%)  0 0/17 (0.00%)  0 0/17 (0.00%)  0 1/12 (8.33%)  1 0/12 (0.00%)  0 0/13 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Cough  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 1/22 (4.55%)  1 1/22 (4.55%)  1
Epistaxis  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Nasal congestion  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Oropharyngeal pain  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Sneezing  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1
Yawning  1  1/24 (4.17%)  1 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Skin and subcutaneous tissue disorders             
Dermatitis contact  1  1/24 (4.17%)  1 1/24 (4.17%)  1 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Dry skin  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 1/22 (4.55%)  1
Ecchymosis  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0
Hair disorder  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Hyperhidrosis  1  4/24 (16.67%)  5 0/24 (0.00%)  0 2/24 (8.33%)  2 1/22 (4.55%)  1 0/22 (0.00%)  0 1/22 (4.55%)  1
Rash  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0
Urticaria  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Vascular disorders             
Flushing  1  2/24 (8.33%)  2 0/24 (0.00%)  0 0/24 (0.00%)  0 1/22 (4.55%)  1 0/22 (0.00%)  0 0/22 (0.00%)  0
Hot flush  1  2/24 (8.33%)  2 0/24 (0.00%)  0 2/24 (8.33%)  2 2/22 (9.09%)  2 0/22 (0.00%)  0 2/22 (9.09%)  2
Peripheral coldness  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0 0/22 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01263197     History of Changes
Other Study ID Numbers: 12598
H9P-EW-LNCI ( Other Identifier: Eli Lilly and Company )
First Submitted: December 16, 2010
First Posted: December 20, 2010
Results First Submitted: February 17, 2018
Results First Posted: October 22, 2018
Last Update Posted: January 29, 2019