Trial Outcomes & Findings for A Study of LY3015014 in Healthy Participants With High Cholesterol (NCT NCT01671085)

NCT ID: NCT01671085

Last Updated: 2019-03-15

Results Overview

Events deemed to be SAEs by the Investigator as related to study drug administration were collected during the study and 30 days following study drug administration. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

13 participants

Primary outcome timeframe

Baseline through study completion (Day 127)

Results posted on

2019-03-15

Participant Flow

Participants who discontinued from the study prior to completion were permitted to be replaced.

Participant milestones

Participant milestones
Measure
1.0 mg/kg of LY3015014
LY3015014: 1.0 milligram per kilogram (mg/kg) of LY3015014 subcutaneously (SQ) on 2 dosing occasions occurring 4 weeks apart (Q4W) (Days 1 and 29).
Placebo
Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).
Overall Study
STARTED
11
2
Overall Study
Received at Least 1 Dose of Study Drug
11
2
Overall Study
COMPLETED
10
2
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
1.0 mg/kg of LY3015014
LY3015014: 1.0 milligram per kilogram (mg/kg) of LY3015014 subcutaneously (SQ) on 2 dosing occasions occurring 4 weeks apart (Q4W) (Days 1 and 29).
Placebo
Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).
Overall Study
Withdrawal by Subject
1
0

Baseline Characteristics

A Study of LY3015014 in Healthy Participants With High Cholesterol

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
1.0 mg/kg of LY3015014
n=11 Participants
LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions (Q4W) (Days 1 and 29).
Placebo
n=2 Participants
Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).
Total
n=13 Participants
Total of all reporting groups
Age, Continuous
55.0 years
STANDARD_DEVIATION 6.3 • n=5 Participants
52.0 years
STANDARD_DEVIATION 4.2 • n=7 Participants
54.5 years
STANDARD_DEVIATION 6.0 • n=5 Participants
Sex: Female, Male
Female
3 Participants
n=5 Participants
0 Participants
n=7 Participants
3 Participants
n=5 Participants
Sex: Female, Male
Male
8 Participants
n=5 Participants
2 Participants
n=7 Participants
10 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
10 Participants
n=5 Participants
2 Participants
n=7 Participants
12 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
Race (NIH/OMB)
White
9 Participants
n=5 Participants
2 Participants
n=7 Participants
11 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
11 Participants
n=5 Participants
2 Participants
n=7 Participants
13 Participants
n=5 Participants
Baseline Low Density Lipoprotein (LDL)-C
134.430 milligrams/deciliter (mg/dL)
STANDARD_DEVIATION 24.559 • n=5 Participants
161.060 milligrams/deciliter (mg/dL)
STANDARD_DEVIATION 1.372 • n=7 Participants
138.527 milligrams/deciliter (mg/dL)
STANDARD_DEVIATION 24.552 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline through study completion (Day 127)

Population: All enrolled participants.

Events deemed to be SAEs by the Investigator as related to study drug administration were collected during the study and 30 days following study drug administration. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Outcome measures
Measure
1.0 mg/kg of LY3015014
n=11 Participants
LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).
Placebo
n=2 Participants
Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).
Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs)
AEs
3 Participants
1 Participants
Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs)
SAEs
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Day 1 and 29: 4 hours (h) and 24 h postdose

Population: Full analysis set (FAS): Data from all randomized participants who received at least 1 dose of the study drug according to the treatment the participants actually received and had evaluable PK data for Cmax.

The Cmax was calculated after each dose of LY3015014.

Outcome measures

Outcome measures
Measure
1.0 mg/kg of LY3015014
n=11 Participants
LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).
Placebo
Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014
After Day 1 dosing
5.06 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 36
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014
After Day 29 dosing
5.57 micrograms per milliliter (µg/mL)
Geometric Coefficient of Variation 58

SECONDARY outcome

Timeframe: Day 1 and 29: 4 h and 24 h postdose

Population: FAS: Data from all randomized participants who received at least 1 dose of study drug according to the treatment the participants actually received and had evaluable PK data for AUCt.

The AUCt was calculated after each dose of LY3015014.

Outcome measures

Outcome measures
Measure
1.0 mg/kg of LY3015014
n=10 Participants
LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).
Placebo
Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).
PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014
After Day 1 dosing
1960 microgram*hour per milliliter (µg*h/mL)
Geometric Coefficient of Variation 37
PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014
After Day 29 dosing
2150 microgram*hour per milliliter (µg*h/mL)
Geometric Coefficient of Variation 46

SECONDARY outcome

Timeframe: Day 1 and 29: 4 h and 24 h postdose

Population: FAS: Data from all randomized participants who received at least 1 dose of study drug according to the treatment the participants actually received and had evaluable PK data for tmax.

tmax was calculated after each dosing of LY3015014 and is reported as the number of days for observed maximum concentration of LY3015014.

Outcome measures

Outcome measures
Measure
1.0 mg/kg of LY3015014
n=11 Participants
LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).
Placebo
Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).
PK: Time of Maximum Concentration (Tmax) of LY3015014
After Day 1 dosing
4 days
Interval 4.0 to 4.0
PK: Time of Maximum Concentration (Tmax) of LY3015014
After Day 29 dosing
5 days
Interval 5.0 to 5.0

SECONDARY outcome

Timeframe: Baseline, Day 43 and Day 57

Population: Pharmacodynamic analyses set: Participants who received at least 1 dose of investigational product according to the treatment actually received and had a baseline measurement and at least 1 post baseline measurement for LDL-C.

Percentage change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed model repeated measures (MMRM) analysis adjusted for baseline measurement. Treatment, day after dosing, and treatment-by-day interaction were included in the model.

Outcome measures

Outcome measures
Measure
1.0 mg/kg of LY3015014
n=11 Participants
LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).
Placebo
n=2 Participants
Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).
Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
Day 43
-49.10 µg/mL
Interval -57.34 to -40.87
1.38 µg/mL
Interval -17.51 to 20.27
Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
Day 57
-37.53 µg/mL
Interval -45.79 to -29.27
7.58 µg/mL
Interval -11.31 to 26.47

Adverse Events

1.0 mg/kg of LY3015014

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
1.0 mg/kg of LY3015014
n=11 participants at risk
LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions Q4W (Days 1 and 29).
Placebo
n=2 participants at risk
Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29).
Gastrointestinal disorders
Faeces discoloured
9.1%
1/11 • Number of events 1 • Baseline through Study Completion (Day 127)
0.00%
0/2 • Baseline through Study Completion (Day 127)
General disorders
Chills
9.1%
1/11 • Number of events 1 • Baseline through Study Completion (Day 127)
0.00%
0/2 • Baseline through Study Completion (Day 127)
General disorders
Fatigue
9.1%
1/11 • Number of events 1 • Baseline through Study Completion (Day 127)
0.00%
0/2 • Baseline through Study Completion (Day 127)
General disorders
Injection site inflammation
9.1%
1/11 • Number of events 1 • Baseline through Study Completion (Day 127)
0.00%
0/2 • Baseline through Study Completion (Day 127)
Infections and infestations
Fungal skin infection
9.1%
1/11 • Number of events 1 • Baseline through Study Completion (Day 127)
0.00%
0/2 • Baseline through Study Completion (Day 127)
Investigations
Blood creatine phosphokinase increased
9.1%
1/11 • Number of events 1 • Baseline through Study Completion (Day 127)
0.00%
0/2 • Baseline through Study Completion (Day 127)
Musculoskeletal and connective tissue disorders
Pain in extremity
9.1%
1/11 • Number of events 1 • Baseline through Study Completion (Day 127)
0.00%
0/2 • Baseline through Study Completion (Day 127)
Nervous system disorders
Headache
18.2%
2/11 • Number of events 2 • Baseline through Study Completion (Day 127)
50.0%
1/2 • Number of events 1 • Baseline through Study Completion (Day 127)
Renal and urinary disorders
Nephrolithiasis
9.1%
1/11 • Number of events 1 • Baseline through Study Completion (Day 127)
0.00%
0/2 • Baseline through Study Completion (Day 127)
Vascular disorders
Hot flush
9.1%
1/11 • Number of events 1 • Baseline through Study Completion (Day 127)
0.00%
0/2 • Baseline through Study Completion (Day 127)

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60