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Trial record 2 of 1892 for:    "Depressive Disorder" [DISEASE] AND Rating AND Major Depressive Disorder

A Study of LY2216684 in Major Depressive Disorder in Patients Taking Selective Serotonin Reuptake Inhibitors

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: NCT01263223
Recruitment Status : Completed
First Posted : December 20, 2010
Results First Posted : October 23, 2018
Last Update Posted : October 23, 2018
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: Placebo
Enrollment 24
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 18-mg LY2216684; Placebo; 36-mg LY2216684 or Placebo Placebo; 18-mg LY2216684; Placebo or 36-mg LY2216684
Hide Arm/Group Description

Period 1: 18-milligram (mg) LY2216684 (LY) administered orally once daily on Days 1-4

Period 2: Placebo administered orally, once daily on Days 1-4

Period 3: 36-mg LY2216684 or Placebo administered orally, once daily on Days 1-4

Period 1: Placebo administered orally, once daily on Days 1-4

Period 2: 18-mg LY2216684 administered orally, once daily on Days 1-4

Period 3: 36-mg LY2216684 or Placebo administered orally, once daily on Days 1-4

Period Title: Period 1
Started 12 12
Completed 12 12
Not Completed 0 0
Period Title: 3-Day Washout
Started 12 12
Completed 12 12
Not Completed 0 0
Period Title: Period 2
Started 12 12
Completed 12 11
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
Period Title: Period 3
Started 12 11
Completed 12 11
Not Completed 0 0
Period Title: 7-day Follow-up
Started 12 11
Completed 11 [1] 10 [2]
Not Completed 1 1
Reason Not Completed
Withdrawal by Subject             0             1
Lost to Follow-up             1             0
[1]
One participant who did not complete received Placebo in Period 3.
[2]
One participant who did not complete received 36-mg LY2216684 in Period 3.
Arm/Group Title Overall Study Participants
Hide Arm/Group Description

Period 1: 18-mg LY2216684 or Placebo administered orally, once daily on Days 1-4.

Period 2: Participants who received LY2216684 in Period 1, then received Placebo administered orally, once daily on Days 1-4 in Period 2. Participants who received Placebo in Period 1, then received 18-mg LY2216684 administered orally, once daily on Days 1-4 in Period 2.

Period 3: 36-mg LY2216684 or Placebo administered orally, once daily on Days 1-4.

Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
All enrolled participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
43.4  (13.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
15
  62.5%
Male
9
  37.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Hispanic or Latino
2
   8.3%
Not Hispanic or Latino
22
  91.7%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
American Indian or Alaska Native
1
   4.2%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
3
  12.5%
White
20
  83.3%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
 100.0%
1.Primary Outcome
Title Maximum and Mean Change From Baseline in Ambulatory Heart Rate on Day 1
Hide Description Heart rate was determined during ambulatory blood pressure monitoring (ABPM). Mean pre-dose ABPM values from Day 1 in Period 1 were used as baseline. Maximum and mean changes in ABPM heart rate were determined from a 24-hour continuous ABPM monitoring for Day 1 (0 to 24 hours). Least Squares (LS) mean changes from baseline were calculated with a mixed effects model including sequence, period, study day, treatment groups, and interaction between treatment groups and study day as fixed effects, and subject as random effect.
Time Frame Baseline through the 24-hour interval on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with a baseline observation and at least 1 post-baseline observation on Day 1 were included in the analyses. Observations with 18-mg LY2216684 included Periods 1 and 2. Observations with Placebo included Periods 1, 2, and 3. Therefore, some participants contributed 2 Placebo observations to the overall data.
Arm/Group Title 18-mg LY2216684 Placebo
Hide Arm/Group Description:
Participants received a single, oral dose of 18-mg LY2216684 each day over 4 days.
Participants received a single, oral dose of Placebo each day over 4 days.
Overall Number of Participants Analyzed 23 23
Overall Number of Units Analyzed
Type of Units Analyzed: Observations
23 27
Least Squares Mean (90% Confidence Interval)
Unit of Measure: beats per minute (bpm)
Mean Change
13.3
(9.9 to 16.7)
3.6
(0.3 to 6.9)
Maximum Change
57.5
(50.9 to 64.1)
33.1
(27.0 to 39.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is for the Mean Change in ABPM heart rate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 9.7
Confidence Interval (2-Sided) 95%
7.4 to 12.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is for the Maximum Change in ABPM heart rate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 24.4
Confidence Interval (2-Sided) 95%
17.9 to 30.9
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maximum and Mean Change From Baseline in Ambulatory Heart Rate on Day 4
Hide Description Heart rate was determined during ABPM. Mean pre-dose ABPM values from Day 1 in Period 1 were used as baseline. Maximum and mean changes in ABPM heart rate were determined from 24 hour continuous ABPM monitoring for Day 4 (0 to 24 hours). LS mean changes from baseline were calculated with a mixed effects model including sequence, period, study day, treatment groups, and interaction between treatment groups and study day as fixed effects, and subject as random effect.
Time Frame Baseline through the 24-hour interval on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with a baseline observation and at least 1 post-baseline observation on Day 4 were included in the analyses. Observations with 18-mg LY2216684 were made in Periods 1 and 2. Observations with Placebo included Periods 1, 2, and 3. Therefore, some participants contributed 2 Placebo observations to the overall data.
Arm/Group Title 18-mg LY2216684 Placebo
Hide Arm/Group Description:
Participants received a single, oral dose of 18-mg LY2216684 each day over 4 days.
Participants received a single, oral dose of Placebo each day over 4 days.
Overall Number of Participants Analyzed 22 23
Overall Number of Units Analyzed
Type of Units Analyzed: Observations
22 27
Least Squares Mean (90% Confidence Interval)
Unit of Measure: beats per minute (bpm)
Mean Change
16.6
(13.2 to 20.1)
3.0
(-0.3 to 6.3)
Maximum Change
58.7
(52.1 to 65.4)
31.1
(25.0 to 37.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is for the Mean Change in ABPM heart rate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 13.6
Confidence Interval (2-Sided) 95%
11.3 to 15.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is for the Maximum Change in ABPM heart rate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 27.6
Confidence Interval (2-Sided) 95%
21.1 to 34.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Maximum and Mean Change From Baseline in Ambulatory Systolic and Diastolic Blood Pressure During Treatment With 18-mg LY2216684 or Placebo on Day 1
Hide Description Blood pressure (BP) was determined with ABPM. Mean pre-dose ABPM values from Day 1 in Period 1 were used as baseline. Changes in ABPM BP were determined from a 24-hour continuous ABPM monitoring for Day 1. LS mean changes from baseline were calculated with a mixed effects model including sequence, period, study day, treatment groups, and interaction between treatment groups and study day as fixed effects, and subject as random effect.
Time Frame Baseline through the 24-hour interval on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with a baseline observation and at least 1 post-baseline observation on Day 1 were included in the analyses. Observations with 18-mg LY2216684 included Periods 1 and 2. Observations with Placebo included Periods 1, 2, and 3. Therefore, some participants contributed 2 Placebo observations to the overall data.
Arm/Group Title 18-mg LY2216684 Placebo
Hide Arm/Group Description:
Participants received a single, oral dose of 18-mg LY2216684 each day over 4 days.
Participants received a single, oral dose of Placebo each day over 4 days.
Overall Number of Participants Analyzed 23 23
Overall Number of Units Analyzed
Type of Units Analyzed: Observations
23 27
Least Squares Mean (90% Confidence Interval)
Unit of Measure: millimeter of mercury (mm Hg)
Mean Change, Systolic BP
3.0
(-0.2 to 6.1)
-3.4
(-6.3 to -0.4)
Maximum Change, Systolic BP
28.8
(24.6 to 33.1)
21.8
(17.9 to 25.6)
Mean Change, Diastolic BP
0.8
(-1.6 to 3.2)
-4.7
(-7.0 to -2.4)
Maximum Change, Diastolic BP
24.3
(21.0 to 27.7)
18.7
(15.6 to 21.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is for the Mean Change in ABPM systolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.3
Confidence Interval (2-Sided) 95%
3.9 to 8.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0025
Comments P-value is for the Maximum Change in ABPM systolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.1
Confidence Interval (2-Sided) 95%
2.6 to 11.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is for the Mean Change in ABPM diastolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.51
Confidence Interval (2-Sided) 95%
3.81 to 7.21
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments P-value is for the Maximum Change in ABPM diastolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.66
Confidence Interval (2-Sided) 95%
2.13 to 9.20
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Maximum and Mean Change From Baseline in Ambulatory Systolic and Diastolic Blood Pressure During Treatment With 18-mg LY2216684 or Placebo on Day 4
Hide Description BP was determined with ABPM. Mean pre-dose ABPM values from Day 1 in Period 1 were used as baseline. Changes in ABPM BP were determined from a 24-hour continuous ABPM monitoring for Day 4. LS mean changes from baseline were calculated with a mixed effects model including sequence, period, study day, treatment groups, and interaction between treatment groups and study day as fixed effects, and subject as random effect.
Time Frame Baseline through the 24-hour interval on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with a baseline observation and at least 1 post-baseline observation on Day 4 were included in the analyses. Observations with 18-mg LY2216684 included Periods 1 and 2. Observations with Placebo included Periods 1, 2, and 3. Therefore, some participants contributed 2 Placebo observations to the overall data.
Arm/Group Title 18-mg LY2216684 Placebo
Hide Arm/Group Description:
Participants received a single, oral dose of 18-mg LY2216684 each day over 4 days.
Participants received a single, oral dose of Placebo each day over 4 days.
Overall Number of Participants Analyzed 22 23
Overall Number of Units Analyzed
Type of Units Analyzed: Observations
22 27
Least Squares Mean (90% Confidence Interval)
Unit of Measure: millimeter of mercury (mm Hg)
Mean Change, Systolic BP
-0.3
(-3.4 to 2.8)
-3.2
(-6.2 to -0.2)
Maximum Change, Systolic BP
24.1
(19.9 to 28.4)
21.4
(17.6 to 25.3)
Mean Change, Diastolic BP
0.04
(-2.4 to 2.4)
-5.1
(-7.4 to -2.8)
Maximum Change, Diastolic BP
22.6
(19.3 to 26.0)
16.1
(13.0 to 19.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0224
Comments P-value is for the Mean Change in ABPM systolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.90
Confidence Interval (2-Sided) 95%
0.418 to 5.38
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2453
Comments P-value is for the Maximum Change in ABPM systolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.70
Confidence Interval (2-Sided) 95%
-1.88 to 7.29
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value if for the Mean Change in ABPM diastolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.10
Confidence Interval (2-Sided) 95%
3.37 to 6.82
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments P-value is for the Maximum Change in ABPM diastolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.53
Confidence Interval (2-Sided) 95%
2.95 to 10.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Maximum and Mean Change From Baseline in ABPM Heart Rate During Treatment With 36-mg LY2216684 or Placebo on Day 4
Hide Description Heart rate was determined with ABPM. Mean pre-dose ABPM values from Day 1 in Period 1 were used as baseline. Changes in ABPM heart rate were determined from a 24-hour continuous ABPM monitoring for Day 4. LS mean changes from baseline were calculated with a mixed effects model including sequence, period, study day, treatment groups, and interaction between treatment groups and study day as fixed effects, and subject as random effect.
Time Frame Baseline through the 24-hour interval on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with a baseline observation and at least 1 post-baseline observation on Day 4 were included in the analyses. Observations with 36-mg LY2216684 included Period 3. Observations with Placebo included Periods 1, 2, and 3. Therefore, some participants contributed 2 Placebo observations to the overall data.
Arm/Group Title 36-mg LY2216684 Placebo
Hide Arm/Group Description:
Participants received a single, oral dose of 36-mg LY2216684 each day over 4 days.
Participants received a single, oral dose of Placebo each day over 4 days.
Overall Number of Participants Analyzed 18 23
Overall Number of Units Analyzed
Type of Units Analyzed: Observations
18 27
Least Squares Mean (90% Confidence Interval)
Unit of Measure: beats per minute (bpm)
Mean Change
15.8
(11.8 to 19.7)
3.0
(-0.3 to 6.3)
Maximum Change
54.1
(45.4 to 62.7)
31.1
(25.0 to 37.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 36-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value is for the Mean Change in ABPM heart rate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 12.8
Confidence Interval (2-Sided) 95%
8.7 to 16.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 36-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments P-value is for the Maximum Change in ABPM heart rate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 23.0
Confidence Interval (2-Sided) 95%
11.4 to 34.5
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Maximum and Mean Change From Baseline in ABPM Systolic and Diastolic Blood Pressure During Treatment With 36-mg LY2216684 or Placebo on Day 4
Hide Description BP was determined with ABPM. Mean pre-dose ABPM values from Day 1 in Period 1 were used as baseline. Changes in ABPM BP were determined from a 24-hour continuous ABPM monitoring for Day 4. LS mean changes from baseline were calculated with a mixed effects model including sequence, period, study day, treatment groups, and interaction between treatment groups and study day as fixed effects, and subject as random effect.
Time Frame Baseline through the 24-hour interval on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with a baseline observation and at least 1 post-baseline observation on Day 4 were included in the analyses. Observations with 36-mg LY2216684 included Period 3. Observations with Placebo included Periods 1, 2, and 3. Therefore, some participants contributed 2 Placebo observations to the overall data.
Arm/Group Title 36-mg LY2216684 Placebo
Hide Arm/Group Description:
Participants received a single, oral dose of 36-mg LY2216684 each day over 4 days.
Participants received a single, oral dose of Placebo each day over 4 days.
Overall Number of Participants Analyzed 18 23
Overall Number of Units Analyzed
Type of Units Analyzed: Observations
18 27
Least Squares Mean (90% Confidence Interval)
Unit of Measure: millimeter of mercury (mm Hg)
Mean Change, Systolic BP
-0.4
(-4.2 to 3.4)
-3.2
(-6.2 to -0.2)
Maximum Change, Systolic BP
29.0
(23.2 to 34.7)
21.4
(17.6 to 25.3)
Mean Change, Diastolic BP
-1.5
(-4.3 to 1.4)
-5.1
(-7.4 to -2.8)
Maximum Change, Diastolic BP
16.6
(12.1 to 21.2)
16.1
(13.0 to 19.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 36-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2120
Comments P-value is for the Mean Change in ABPM Systolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-1.6 to 7.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 36-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0640
Comments P-value is for the Maximum Change in ABPM Systolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.6
Confidence Interval (2-Sided) 95%
-0.4 to 15.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 36-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0211
Comments P-value is for the Mean Change in ABPM Diastolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.6
Confidence Interval (2-Sided) 95%
0.5 to 6.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 36-mg LY2216684, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8719
Comments P-value is for the Maximum Change in ABPM Diastolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-5.7 to 6.8
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Maximum and Mean Change From Baseline in ABPM Heart Rate During Treatment With 18-mg LY2216684 or 36-mg LY2216684 on Day 4
Hide Description Heart rate was determined with ABPM. Mean pre-dose ABPM values from Day 1 in Period 1 were used as baseline. Changes in ABPM heart rate were determined from a 24-hour continuous ABPM monitoring for Day 4. LS mean changes from baseline were calculated with a mixed effects model including sequence, period, study day, treatment groups, and interaction between treatment groups and study day as fixed effects, and subject as random effect.
Time Frame Baseline through the 24-hour interval on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with a baseline observation and at least 1 post-baseline observation on Day 4 were included in the analyses.
Arm/Group Title 18-mg LY2216684 36-mg LY2216684
Hide Arm/Group Description:
Participants received a single, oral dose of 18-mg LY2216684 each day over 4 days.
Participants received a single, oral dose of 36-mg LY2216684 each day over 4 days.
Overall Number of Participants Analyzed 22 18
Least Squares Mean (90% Confidence Interval)
Unit of Measure: beats per minute (bpm)
Mean Change
16.6
(13.2 to 20.1)
15.8
(11.8 to 19.7)
Maximum Change
58.7
(52.1 to 65.4)
54.1
(45.4 to 62.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, 36-mg LY2216684
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7133
Comments P-value is for the Mean Change in ABPM heart rate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-5.3 to 3.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, 36-mg LY2216684
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4638
Comments P-value is for the Maximum Change in ABPM heart rate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.7
Confidence Interval (2-Sided) 95%
-17.2 to 7.9
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Maximum and Mean Change From Baseline in ABPM Systolic and Diastolic Blood Pressure During Treatment With 18-mg LY2216684 or 36-mg LY2216684 on Day 4
Hide Description BP was determined with ABPM. Mean pre-dose ABPM values from Day 1 in Period 1 were used as baseline. Changes in ABPM BP were determined from a 24-hour continuous ABPM monitoring for Day 4. LS mean changes from baseline were calculated with a mixed effects model including sequence, period, study day, treatment groups, and interaction between treatment groups and study day as fixed effects, and subject as random effect.
Time Frame Baseline through the 24-hour interval on Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with a baseline observation and at least 1 post-baseline observation on Day 4 were included in the analyses.
Arm/Group Title 18-mg LY2216684 36-mg LY2216684
Hide Arm/Group Description:
Participants received a single, oral dose of 18-mg LY2216684 each day over 4 days.
Participants received a single, oral dose of 36-mg LY2216684 each day over 4 days.
Overall Number of Participants Analyzed 22 18
Least Squares Mean (90% Confidence Interval)
Unit of Measure: millimeter of mercury (mm Hg)
Mean Change, Systolic BP
-0.3
(-3.4 to 2.8)
-0.4
(-4.2 to 3.4)
Maximum Change, Systolic BP
24.1
(19.9 to 28.4)
29.0
(23.2 to 34.7)
Mean Change, Diastolic BP
0.04
(-2.4 to 2.4)
-1.5
(-4.3 to 1.4)
Maximum Change, Diastolic BP
22.6
(19.3 to 26.0)
16.6
(12.1 to 21.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, 36-mg LY2216684
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9609
Comments P-value is for the Mean Change in ABPM Systolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-4.9 to 4.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, 36-mg LY2216684
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2731
Comments P-value is for the Maximum Change in ABPM Systolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.8
Confidence Interval (2-Sided) 95%
-3.9 to 13.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, 36-mg LY2216684
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3779
Comments P-value is for the Mean Change in ABPM Diastolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-4.8 to 1.8
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 18-mg LY2216684, 36-mg LY2216684
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0828
Comments P-value is for the Maximum Change in ABPM Diastolic BP.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.0
Confidence Interval (2-Sided) 95%
-12.8 to 0.8
Estimation Comments [Not Specified]
Time Frame Periods 1, 2, and 3 through 7-day follow-up
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 18-mg LY2216684 36-mg LY2216684 Placebo
Hide Arm/Group Description Participants received a single, oral dose of 18-mg LY2216684 each day over 4 days. Participants received a single, oral dose of 36-mg LY2216684 each day over 4 days. Participants received a single, oral dose of Placebo each day over 4 days.
All-Cause Mortality
18-mg LY2216684 36-mg LY2216684 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
18-mg LY2216684 36-mg LY2216684 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/24 (0.00%)      1/19 (5.26%)      0/24 (0.00%)    
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism  1  0/24 (0.00%)  0 1/19 (5.26%)  1 0/24 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
18-mg LY2216684 36-mg LY2216684 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/24 (83.33%)      12/19 (63.16%)      14/24 (58.33%)    
Eye disorders       
Dry eye  1  0/24 (0.00%)  0 1/19 (5.26%)  1 0/24 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain upper  1  0/24 (0.00%)  0 1/19 (5.26%)  1 0/24 (0.00%)  0
Constipation  1  2/24 (8.33%)  2 0/19 (0.00%)  0 1/24 (4.17%)  1
Dry mouth  1  0/24 (0.00%)  0 1/19 (5.26%)  1 1/24 (4.17%)  1
Nausea  1  3/24 (12.50%)  3 5/19 (26.32%)  5 0/24 (0.00%)  0
Vomiting  1  3/24 (12.50%)  3 0/19 (0.00%)  0 0/24 (0.00%)  0
General disorders       
Feeling cold  1  0/24 (0.00%)  0 1/19 (5.26%)  1 0/24 (0.00%)  0
Vessel puncture site pain  1  0/24 (0.00%)  0 0/19 (0.00%)  0 2/24 (8.33%)  2
Investigations       
Blood pressure increased  1  1/24 (4.17%)  1 1/19 (5.26%)  1 1/24 (4.17%)  1
Heart rate increased  1  9/24 (37.50%)  9 3/19 (15.79%)  3 1/24 (4.17%)  1
Metabolism and nutrition disorders       
Decreased appetite  1  0/24 (0.00%)  0 3/19 (15.79%)  3 0/24 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Back pain  1  0/24 (0.00%)  0 1/19 (5.26%)  1 0/24 (0.00%)  0
Nervous system disorders       
Dizziness  1  4/24 (16.67%)  5 2/19 (10.53%)  2 1/24 (4.17%)  1
Headache  1  2/24 (8.33%)  2 1/19 (5.26%)  1 3/24 (12.50%)  4
Paraesthesia  1  3/24 (12.50%)  3 1/19 (5.26%)  1 0/24 (0.00%)  0
Somnolence  1  0/24 (0.00%)  0 1/19 (5.26%)  1 0/24 (0.00%)  0
Psychiatric disorders       
Abnormal dreams  1  2/24 (8.33%)  2 1/19 (5.26%)  1 0/24 (0.00%)  0
Insomnia  1  1/24 (4.17%)  1 2/19 (10.53%)  2 3/24 (12.50%)  4
Renal and urinary disorders       
Dysuria  1  2/24 (8.33%)  2 1/19 (5.26%)  1 0/24 (0.00%)  0
Micturition urgency  1  0/24 (0.00%)  0 1/19 (5.26%)  1 0/24 (0.00%)  0
Urinary hesitation  1  2/24 (8.33%)  2 2/19 (10.53%)  2 0/24 (0.00%)  0
Reproductive system and breast disorders       
Menstrual disorder  1  1/15 (6.67%)  1 0/12 (0.00%)  0 0/15 (0.00%)  0
Metrorrhagia  1  0/15 (0.00%)  0 0/12 (0.00%)  0 1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders       
Cough  1  2/24 (8.33%)  2 0/19 (0.00%)  0 0/24 (0.00%)  0
Skin and subcutaneous tissue disorders       
Hyperhidrosis  1  0/24 (0.00%)  0 2/19 (10.53%)  2 1/24 (4.17%)  1
Vascular disorders       
Hot flush  1  3/24 (12.50%)  3 1/19 (5.26%)  1 2/24 (8.33%)  2
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
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01263223     History of Changes
Other Study ID Numbers: 12607
H9P-EW-LNCP ( 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 23, 2018
Last Update Posted: October 23, 2018