A Study of LY3015014 in Otherwise Healthy Participants With High Low-density Lipoprotein (LDL) Cholesterol
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01618916
Collaborator
(none)
51
2
6
8
25.5
3.2
Study Details
Study Description
Brief Summary
This is a phase 1 study in otherwise healthy participants with high LDL cholesterol. Following multiple doses of LY3015014, the safety and tolerability of the drug, how the body handles the drug, and the drug's effect on the body will be evaluated. Participants will participate in the study for approximately 3 months not including screening. Screening is required within 42 days prior to the start of the study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
51 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
A Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3015014 in Japanese and Non-Japanese Subjects With Elevated LDL-C
Study Start Date
:
Jun 1, 2012
Actual Primary Completion Date
:
Feb 1, 2013
Actual Study Completion Date
:
Feb 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1.0 milligrams per kilogram (mg/kg) LY3015014 Every 2 Weeks 1.0 mg/kg LY3015014 given subcutaneously (SC) once every 2 weeks for 29 days. |
Drug: LY3015014
Administered SC
|
| Experimental: 1.0 mg/kg LY3015014 Every 4 Weeks 1.0 mg/kg LY3015014 given SC once every 4 weeks for 29 days. |
Drug: LY3015014
Administered SC
|
| Experimental: 3.0 mg/kg LY3015014 Every 2 Weeks 3.0 mg/kg LY3015014 given SC once every 2 weeks for 29 days. |
Drug: LY3015014
Administered SC
|
| Experimental: 3.0 mg/kg LY3015014 Every 4 Weeks 3.0 mg/kg LY3015014 given SC once every 4 weeks for 29 days. |
Drug: LY3015014
Administered SC
|
| Placebo Comparator: Placebo Every 2 Weeks Saline injection (to match LY3015014) given SC once every 2 weeks for 29 days. |
Other: Placebo
Administered SC
|
| Placebo Comparator: Placebo Every 4 Weeks Saline injection (to match LY3015014) given SC once every 4 weeks for 29 days. |
Other: Placebo
Administered SC
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) [Baseline through study completion (up to Day 127)]
TEAEs were defined as SAEs and other non-serious AEs that occurred or worsened after study treatment. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events section of this report.
Secondary Outcome Measures
- Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 [First Dose (Day 1) and Last Dose (Day 29): Predose, 4 Hours and 24 Hours Postdose]
The Cmax following the first dose and last dose of LY3015014 is reported.
- PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) [First Dose (Day 1) and Last Dose (Day 29): Predose, 4 Hours and 24 Hours Postdose]
The AUC(0-tau) following the first dose and last dose of LY3015014 is reported.
- PK: Time of Maximum Concentration (Tmax) of LY3015014 [First Dose: Predose (Day 1) up to Week 4 postdose and Last Dose: predose (Day 29) up to Week 14 postdose]
The tmax following the first dose and last dose of LY3015014 is reported.
- Percent Change From Baseline to Days 43, 57, and 127 in LDL-C [Baseline, Day 43, Day 57, and Day 127]
Percent change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed effect model repeated measures (MMRM) analysis adjusted for baseline measurement, treatment, day after dosing, and treatment by day interaction.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Participants must be healthy males or females without childbearing potential as determined by medical history and physical examination, including first-generation Japanese participants
-
Have body mass indexes of 18 to 35 kilograms per meter square (kg/m^2), inclusive, at screening
-
Have screening low-density lipoprotein cholesterol (LDL-C) of between 100 and 180 milligrams per deciliter (mg/dL), inclusive
Exclusion Criteria:
-
Have known allergies to compounds related to LY3015014 or any components of the formulation or known clinically significant hypersensitivity to biologic agents
-
Have a history of atopy, significant allergies to humanized monoclonal antibodies, clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions [including but not limited to erythema multiforme major, linear immunoglobulin (Ig)A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis)
-
Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, of constituting a risk when taking the study medication, or of interfering with the interpretation of data
-
Have received any vaccine(s) within 1 month of LY3015014 dosing or intend to do so during the study
-
Have received treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) prior to dosing
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Honolulu | Hawaii | United States | 96814 |
| 2 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Dallas | Texas | United States | 75247 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri, 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01618916
Other Study ID Numbers:
- 14354
- I5S-EW-EFJB
First Posted:
Jun 13, 2012
Last Update Posted:
Mar 15, 2019
Last Verified:
Feb 1, 2019
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W | Placebo Q2W | Placebo Q4W |
|---|---|---|---|---|---|---|
| Arm/Group Description | LY3015014: 1.0 milligrams per kilogram (mg/kg) given as subcutaneous (SC) injection every 2 weeks (Q2W) on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 1.0 mg/kg given as SC injection every 4 weeks (Q4W) on Days 1 and 29 for a total of 2 doses. | LY3015014: 3.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 3.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | Placebo given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | Placebo given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. |
| Period Title: Overall Study | ||||||
| STARTED | 12 | 10 | 11 | 9 | 5 | 4 |
| Received At Least 1 Dose of Study Drug | 12 | 10 | 11 | 9 | 5 | 4 |
| COMPLETED | 10 | 9 | 10 | 7 | 4 | 4 |
| NOT COMPLETED | 2 | 1 | 1 | 2 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W | Placebo Q2W | Placebo Q4W | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | LY3015014: 1.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 1.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | LY3015014: 3.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 3.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | Placebo given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | Placebo given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | Total of all reporting groups |
| Overall Participants | 12 | 10 | 11 | 9 | 5 | 4 | 51 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
52.0
(8.0)
|
46.8
(10.3)
|
53.7
(11.6)
|
51.4
(13.6)
|
49.2
(13.2)
|
47.8
(15.2)
|
50.6
(11.1)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
6
50%
|
3
30%
|
9
81.8%
|
3
33.3%
|
2
40%
|
2
50%
|
25
49%
|
| Male |
6
50%
|
7
70%
|
2
18.2%
|
6
66.7%
|
3
60%
|
2
50%
|
26
51%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||
| Asian |
5
41.7%
|
4
40%
|
3
27.3%
|
3
33.3%
|
1
20%
|
0
0%
|
16
31.4%
|
| Black or African American |
4
33.3%
|
3
30%
|
3
27.3%
|
2
22.2%
|
3
60%
|
2
50%
|
17
33.3%
|
| White |
3
25%
|
3
30%
|
5
45.5%
|
4
44.4%
|
1
20%
|
1
25%
|
17
33.3%
|
| Multiple |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
1
2%
|
| Region of Enrollment (Count of Participants) | |||||||
| United States |
12
100%
|
10
100%
|
11
100%
|
9
100%
|
5
100%
|
4
100%
|
51
100%
|
| Baseline Low-Density Lipoprotein Cholesterol (LDL-C) (milligrams per deciliter (mg/dL)) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [milligrams per deciliter (mg/dL)] |
139.6
(26.1)
|
119.3
(48.1)
|
141.8
(20.2)
|
151.7
(30.6)
|
165.0
(28.9)
|
122.7
(36.0)
|
139.4
(33.8)
|
Outcome Measures
| Title | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) |
|---|---|
| Description | TEAEs were defined as SAEs and other non-serious AEs that occurred or worsened after study treatment. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events section of this report. |
| Time Frame | Baseline through study completion (up to Day 127) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least 1 dose of study drug (LY3015014 or placebo). |
| Arm/Group Title | 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W | Placebo Q2W Plus Placebo Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | LY3015014: 1.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 1.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | LY3015014: 3.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 3.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | Placebo given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses and Q4W on Days 1 and 29 for a total of 2 doses. |
| Measure Participants | 12 | 10 | 11 | 9 | 9 |
| 1 or More TEAEs Related to Study Drug |
4
33.3%
|
3
30%
|
5
45.5%
|
2
22.2%
|
3
60%
|
| Any SAEs |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 |
|---|---|
| Description | The Cmax following the first dose and last dose of LY3015014 is reported. |
| Time Frame | First Dose (Day 1) and Last Dose (Day 29): Predose, 4 Hours and 24 Hours Postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of LY3015014 and had evaluable Cmax data. |
| Arm/Group Title | 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W |
|---|---|---|---|---|
| Arm/Group Description | LY3015014: 1.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 1.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | LY3015014: 3.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 3.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. |
| Measure Participants | 12 | 10 | 10 | 9 |
| First Dose |
4.24
(59)
|
4.82
(53)
|
14.6
(48)
|
17.9
(61)
|
| Last Dose |
9.21
(38)
|
6.64
(31)
|
35.1
(24)
|
23.1
(51)
|
| Title | PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) |
|---|---|
| Description | The AUC(0-tau) following the first dose and last dose of LY3015014 is reported. |
| Time Frame | First Dose (Day 1) and Last Dose (Day 29): Predose, 4 Hours and 24 Hours Postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of LY3015014 and had evaluable AUC(0-tau) data. |
| Arm/Group Title | 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W |
|---|---|---|---|---|
| Arm/Group Description | LY3015014: 1.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 1.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | LY3015014: 3.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 3.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. |
| Measure Participants | 12 | 10 | 10 | 9 |
| First Dose |
1080
(51)
|
2110
(37)
|
3890
(47)
|
8230
(52)
|
| Last Dose |
2450
(35)
|
2810
(24)
|
9440
(17)
|
10900
(44)
|
| Title | PK: Time of Maximum Concentration (Tmax) of LY3015014 |
|---|---|
| Description | The tmax following the first dose and last dose of LY3015014 is reported. |
| Time Frame | First Dose: Predose (Day 1) up to Week 4 postdose and Last Dose: predose (Day 29) up to Week 14 postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of LY3015014 and had evaluable tmax data. |
| Arm/Group Title | 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W |
|---|---|---|---|---|
| Arm/Group Description | LY3015014: 1.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 1.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | LY3015014: 3.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 3.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. |
| Measure Participants | 12 | 10 | 10 | 9 |
| First Dose |
4
|
4
|
4
|
4
|
| Last Dose |
5
|
5
|
5
|
5
|
| Title | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C |
|---|---|
| Description | Percent change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed effect model repeated measures (MMRM) analysis adjusted for baseline measurement, treatment, day after dosing, and treatment by day interaction. |
| Time Frame | Baseline, Day 43, Day 57, and Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized participants who received at least 1 dose of study drug (LY3015014 or placebo) and had a baseline and at least 1 postbaseline measurement for LDL-C. |
| Arm/Group Title | 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W | Placebo Q2W Plus Placebo Q4W |
|---|---|---|---|---|---|
| Arm/Group Description | LY3015014: 1.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 1.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | LY3015014: 3.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 3.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | Placebo given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses and Q4W on Days 1 and 29 for a total of 2 doses. |
| Measure Participants | 10 | 9 | 10 | 7 | 9 |
| Day 43 |
-49.76
|
-47.56
|
-45.20
|
-46.64
|
0.16
|
| Day 57 |
-47.01
|
-44.41
|
-44.20
|
-56.80
|
-12.16
|
| Day 127 |
-7.52
|
-15.09
|
-23.39
|
-18.91
|
-0.99
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 1.0 mg/kg LY3015014 Q2W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effects Model Analysis | |
| Comments | P-value is for Day 43. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -49.92 | |
| Confidence Interval |
() 90% -63.84 to -35.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 1.0 mg/kg LY3015014 Q2W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effects Model Analysis | |
| Comments | P-value is for Day 57. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -34.85 | |
| Confidence Interval |
() 90% -48.78 to -20.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 1.0 mg/kg LY3015014 Q4W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effects Model Analysis | |
| Comments | P-value is for Day 43. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -47.72 | |
| Confidence Interval |
() 90% -62.10 to -33.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 1.0 mg/kg LY3015014 Q4W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effects Model Analysis | |
| Comments | P-value is for Day 57. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -32.26 | |
| Confidence Interval |
() 90% -46.69 to -17.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 3.0 mg/kg LY3015014 Q2W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effects Model Analysis | |
| Comments | P-value is for Day 43. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -45.36 | |
| Confidence Interval |
() 90% -60.07 to -30.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 3.0 mg/kg LY3015014 Q2W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effects Model Analysis | |
| Comments | P-value is for Day 57. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -32.04 | |
| Confidence Interval |
() 90% -46.76 to -17.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | 3.0 mg/kg LY3015014 Q4W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effects Model Analysis | |
| Comments | P-value is for Day 43. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -46.80 | |
| Confidence Interval |
() 90% -61.12 to -32.49 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | 3.0 mg/kg LY3015014 Q4W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effects Model Analysis | |
| Comments | P-value is for Day 57. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -44.64 | |
| Confidence Interval |
() 90% -58.95 to -30.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | 1.0 mg/kg LY3015014 Q2W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.440 |
| Comments | ||
| Method | Mixed Effect Model Analysis | |
| Comments | P-value is for Day 127 | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -6.53 | |
| Confidence Interval |
() 90% -20.51 to 7.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | 1.0 mg/kg LY3015014 Q4W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.108 |
| Comments | ||
| Method | Mixed Effect Model Analysis | |
| Comments | P-value is for Day 127. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -14.10 | |
| Confidence Interval |
() 90% -28.53 to 0.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | 3.0 mg/kg LY3015014 Q2W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.013 |
| Comments | ||
| Method | Mixed Effect Model Analysis | |
| Comments | P-value is for Day 127. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -22.41 | |
| Confidence Interval |
() 90% -37.13 to -7.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | 3.0 mg/kg LY3015014 Q4W, Placebo Q2W Plus Placebo Q4W |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.042 |
| Comments | ||
| Method | Mixed Effect Model Analysis | |
| Comments | P-value is for Day 127. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -17.93 | |
| Confidence Interval |
() 90% -32.42 to -3.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| Arm/Group Title | 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W | Placebo Q2W | Placebo Q4W | ||||||
| Arm/Group Description | LY3015014: 1.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 1.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | LY3015014: 3.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | LY3015014: 3.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | Placebo given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | Placebo given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | ||||||
All Cause Mortality |
||||||||||||
| 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W | Placebo Q2W | Placebo Q4W | |||||||
| 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 | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W | Placebo Q2W | Placebo Q4W | |||||||
| 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 | 0/12 (0%) | 0/10 (0%) | 0/11 (0%) | 0/9 (0%) | 0/5 (0%) | 0/4 (0%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W | Placebo Q2W | Placebo Q4W | |||||||
| 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 | 7/12 (58.3%) | 6/10 (60%) | 8/11 (72.7%) | 7/9 (77.8%) | 3/5 (60%) | 0/4 (0%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Lymphadenopathy | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Cardiac disorders | ||||||||||||
| Palpitations | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||
| Ear pain | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| Abdominal distension | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Abdominal pain | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 |
| Constipation | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 |
| Diarrhoea | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Dyspepsia | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Eructation | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Flatulence | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Gingival swelling | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Haemorrhoids | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 2 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Nausea | 1/12 (8.3%) | 1 | 1/10 (10%) | 1 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 |
| Toothache | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Vomiting | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| General disorders | ||||||||||||
| Application site irritation | 1/12 (8.3%) | 1 | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Fatigue | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Injection site erythema | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 4/11 (36.4%) | 4 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Injection site haemorrhage | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 |
| Injection site pain | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Injection site pruritus | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 3/11 (27.3%) | 3 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Injection site rash | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Injection site reaction | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Injection site swelling | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Oedema peripheral | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Pain | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Infections and infestations | ||||||||||||
| Gingival infection | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Upper respiratory tract infection | 1/12 (8.3%) | 1 | 2/10 (20%) | 2 | 1/11 (9.1%) | 1 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Urinary tract infection | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Viral upper respiratory tract infection | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 2/9 (22.2%) | 2 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||
| Animal bite | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Procedural dizziness | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Wrist fracture | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Back pain | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 1/11 (9.1%) | 1 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Muscle spasms | 0/12 (0%) | 0 | 2/10 (20%) | 2 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 1/5 (20%) | 1 | 0/4 (0%) | 0 |
| Muscle twitching | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/9 (11.1%) | 1 | 1/5 (20%) | 1 | 0/4 (0%) | 0 |
| Myopathy | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| Dizziness | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Headache | 2/12 (16.7%) | 2 | 1/10 (10%) | 1 | 3/11 (27.3%) | 3 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Presyncope | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||
| Dysmenorrhoea | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/3 (0%) | 0 | 0/2 (0%) | 0 | 0/2 (0%) | 0 |
| Menstruation delayed | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/9 (0%) | 0 | 0/3 (0%) | 0 | 0/2 (0%) | 0 | 0/2 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Rhinitis seasonal | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| Ecchymosis | 0/12 (0%) | 0 | 1/10 (10%) | 1 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Pruritus | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Pruritus generalised | 1/12 (8.3%) | 1 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 0/9 (0%) | 0 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
| Rash | 0/12 (0%) | 0 | 0/10 (0%) | 0 | 0/11 (0%) | 0 | 1/9 (11.1%) | 1 | 0/5 (0%) | 0 | 0/4 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
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:
NCT01618916
Other Study ID Numbers:
- 14354
- I5S-EW-EFJB
First Posted:
Jun 13, 2012
Last Update Posted:
Mar 15, 2019
Last Verified:
Feb 1, 2019