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Trial Outcomes & Findings for A Study of LY2969822 in Healthy Participants (NCT NCT02018887)

NCT ID: NCT02018887

Last Updated: 2019-02-21

Results Overview

A summary of other nonserious adverse events (AEs) and all SAEs, regardless of causality, is located in the Reported Adverse Events section.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

99 participants

Primary outcome timeframe

Baseline Through End of Study (up to Week 7)

Results posted on

2019-02-21

Participant Flow

This study had 3 parts. Part A-Single ascending dose, 3-period, crossover study (Cohorts 1-2). Part B-Multiple ascending dose, parallel study (Cohorts 3-7). Part C-Multiple dose, single dose level study (Cohort 8). Each participant enrolled in 1 cohort. Replacement participants received interventions intended for those that discontinued early.

Participant milestones

Participant milestones
Measure
Part A: Cohort 1
Participants were randomised to receive 2 single, oral doses of LY2969822 and 1 oral dose of placebo over the 3 study periods in a crossover fashion. For each study period, it was intended that 6 subjects would receive LY2969822 and 3 subjects would receive placebo. Placebo administered once, orally (PO) at all three periods. 2 milligrams (mg) LY2969822 administered once, PO during period 1. 20 mg LY2969822 administered once, PO during period 2. 40 mg LY2969822 administered once, PO during period 3.
Part A: Cohort 2
Participants were randomised to receive 2 single, oral doses of LY2969822 and 1 oral dose of placebo over the 3 study periods in a crossover fashion. For each study period, it was intended that 6 subjects would receive LY2969822 and 3 subjects would receive placebo. Placebo administered once, PO at all three periods. 6 mg LY2969822 administered once, PO during period 1. 60 mg LY2969822 administered once, PO during period 2. 20 mg LY2969822 administered once, PO during period 3.
Cohorts 3-7 - Placebo
Placebo administered once a day (QD) or twice a day (BID), PO, for 14 days.
Cohort 3 - 20 mg LY2969822 QD
20 mg LY2969822 administered QD, PO, for 14 days.
Cohort 4 - 40 mg LY2969822 QD Titrated
Up to 40 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 3 days, 20 mg QD for 2 days, and 40 mg QD for 9 days.
Cohort 5 - 80 mg LY2969822 QD Titrated
Up to 80 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 2 days, 20 mg QD for 2 days, 40 mg QD for 2 days and 80 mg QD for 8 days.
Cohort 6 - 80 mg LY2969822 BID Titrated
Up to 80 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.
Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, and 40 mg BID for 12 days.
Cohort 8 - Placebo BID
Placebo administered BID, PO, for 14 days.
Cohort 8A - 40 mg LY2969822 BID Titrated
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.)
Cohort 8B - 20 mg LY2969822 BID Titrated
Up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, and 20 mg BID for 10 days.
Part A: Cohorts 1-2: Period 1
STARTED
9
9
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 1
Received One Dose of Study Drug
9
9
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 1
COMPLETED
9
9
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 1
NOT COMPLETED
0
0
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 2
STARTED
9
9
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 2
Received One Dose of Study Drug
9
9
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 2
COMPLETED
9
9
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 2
NOT COMPLETED
0
0
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 3
STARTED
9
9
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 3
Received One Dose of Study Drug
8
9
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 3
COMPLETED
8
9
0
0
0
0
0
0
0
0
0
Part A: Cohorts 1-2: Period 3
NOT COMPLETED
1
0
0
0
0
0
0
0
0
0
0
Part B: Cohorts 3-7 Overall
STARTED
0
0
15
9
9
9
9
9
0
0
0
Part B: Cohorts 3-7 Overall
Received at Least One Dose of Study Drug
0
0
15
9
9
9
9
9
0
0
0
Part B: Cohorts 3-7 Overall
COMPLETED
0
0
15
9
8
9
8
5
0
0
0
Part B: Cohorts 3-7 Overall
NOT COMPLETED
0
0
0
0
1
0
1
4
0
0
0
Part C: Cohort 8 Overall
STARTED
0
0
0
0
0
0
0
0
10
4
7
Part C: Cohort 8 Overall
Received at Least One Dose of Study Drug
0
0
0
0
0
0
0
0
10
4
7
Part C: Cohort 8 Overall
COMPLETED
0
0
0
0
0
0
0
0
7
1
6
Part C: Cohort 8 Overall
NOT COMPLETED
0
0
0
0
0
0
0
0
3
3
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Part A: Cohort 1
Participants were randomised to receive 2 single, oral doses of LY2969822 and 1 oral dose of placebo over the 3 study periods in a crossover fashion. For each study period, it was intended that 6 subjects would receive LY2969822 and 3 subjects would receive placebo. Placebo administered once, orally (PO) at all three periods. 2 milligrams (mg) LY2969822 administered once, PO during period 1. 20 mg LY2969822 administered once, PO during period 2. 40 mg LY2969822 administered once, PO during period 3.
Part A: Cohort 2
Participants were randomised to receive 2 single, oral doses of LY2969822 and 1 oral dose of placebo over the 3 study periods in a crossover fashion. For each study period, it was intended that 6 subjects would receive LY2969822 and 3 subjects would receive placebo. Placebo administered once, PO at all three periods. 6 mg LY2969822 administered once, PO during period 1. 60 mg LY2969822 administered once, PO during period 2. 20 mg LY2969822 administered once, PO during period 3.
Cohorts 3-7 - Placebo
Placebo administered once a day (QD) or twice a day (BID), PO, for 14 days.
Cohort 3 - 20 mg LY2969822 QD
20 mg LY2969822 administered QD, PO, for 14 days.
Cohort 4 - 40 mg LY2969822 QD Titrated
Up to 40 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 3 days, 20 mg QD for 2 days, and 40 mg QD for 9 days.
Cohort 5 - 80 mg LY2969822 QD Titrated
Up to 80 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 2 days, 20 mg QD for 2 days, 40 mg QD for 2 days and 80 mg QD for 8 days.
Cohort 6 - 80 mg LY2969822 BID Titrated
Up to 80 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.
Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, and 40 mg BID for 12 days.
Cohort 8 - Placebo BID
Placebo administered BID, PO, for 14 days.
Cohort 8A - 40 mg LY2969822 BID Titrated
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.)
Cohort 8B - 20 mg LY2969822 BID Titrated
Up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, and 20 mg BID for 10 days.
Part A: Cohorts 1-2: Period 3
Adverse Event
1
0
0
0
0
0
0
0
0
0
0
Part B: Cohorts 3-7 Overall
Adverse Event
0
0
0
0
1
0
1
4
0
0
0
Part C: Cohort 8 Overall
Adverse Event
0
0
0
0
0
0
0
0
1
3
0
Part C: Cohort 8 Overall
Physician Decision
0
0
0
0
0
0
0
0
2
0
1

Baseline Characteristics

A Study of LY2969822 in Healthy Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Part A: Cohorts 1-2
n=18 Participants
Part A Single Ascending Dose (SAD): Cohort 1 received placebo, 2 mg, 20 mg, or 40 mg LY2969822 PO, once, in each of 3 study periods. Cohort 2 received placebo, 6 mg, 60 mg, or 20 mg LY2969822 PO, once, in each of 3 study periods. At least 5 days elapsed between doses of study drug.
Part B: Placebo
n=15 Participants
Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.)
Part B: Cohorts 3
n=9 Participants
Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.)
Part B: Cohorts 4
n=9 Participants
Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.)
Part B: Cohorts 5
n=9 Participants
Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.)
Part B: Cohorts 6
n=9 Participants
Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.)
Part B: Cohorts 7
n=9 Participants
Part B Multiple Ascending Dose (MAD): Participants were assigned to 1 of 5 dosing cohorts (Cohorts 3 - 7). Cohort 3 received either placebo or 20 mg LY2969822 QD, PO, for 14 days. Cohort 4 received either placebo or up to 40 mg LY2969822 QD, PO, for 14 days (Titration: 6 mg QD for 3 days; 20 mg QD for 2 days, and 40 mg QD for 9 days.) Cohort 5 received placebo or up to 80 mg LY2969822 QD, PO, for 14 days. (Titration: 6 mg QD for 2 days; 20 mg QD for 2 days; 40 mg QD for 2 days and 80 mg QD for 8 days.) Cohort 6 received either placebo or up to 80 mg LY2969822 BID, PO for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.) Cohort 7 received either placebo or up to 40 mg LY2969822 BID, PO for 14 days with rapid titration. (Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, 40 mg BID for 12 days.)
Part C: Cohort 8
n=21 Participants
Part C Multiple Dose, Single Dose Level: Cohort 8A received either placebo or up to 40 LY2969822 BID, PO, for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.) Cohort 8B received either placebo or up to 20 mg LY2969822 BID, PO, for 14 days. (Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, and 20 mg BID for 10 days.)
Total
n=99 Participants
Total of all reporting groups
Age, Continuous
Part A
35.1 years
STANDARD_DEVIATION 9.5 • n=5 Participants
NA years
STANDARD_DEVIATION NA • n=7 Participants
NA years
STANDARD_DEVIATION NA • n=5 Participants
NA years
STANDARD_DEVIATION NA • n=4 Participants
NA years
STANDARD_DEVIATION NA • n=21 Participants
NA years
STANDARD_DEVIATION NA • n=10 Participants
NA years
STANDARD_DEVIATION NA • n=115 Participants
NA years
STANDARD_DEVIATION NA • n=24 Participants
35.1 years
STANDARD_DEVIATION 9.5 • n=42 Participants
Age, Continuous
Part B
NA years
STANDARD_DEVIATION NA • n=5 Participants
32.6 years
STANDARD_DEVIATION 7.6 • n=7 Participants
32.7 years
STANDARD_DEVIATION 7.4 • n=5 Participants
34.6 years
STANDARD_DEVIATION 6.8 • n=4 Participants
32.2 years
STANDARD_DEVIATION 6.7 • n=21 Participants
31.6 years
STANDARD_DEVIATION 5.7 • n=10 Participants
35.1 years
STANDARD_DEVIATION 10.6 • n=115 Participants
NA years
STANDARD_DEVIATION NA • n=24 Participants
33.1 years
STANDARD_DEVIATION 7.4 • n=42 Participants
Age, Continuous
Part C
NA years
STANDARD_DEVIATION NA • n=5 Participants
NA years
STANDARD_DEVIATION NA • n=7 Participants
NA years
STANDARD_DEVIATION NA • n=5 Participants
NA years
STANDARD_DEVIATION NA • n=4 Participants
NA years
STANDARD_DEVIATION NA • n=21 Participants
NA years
STANDARD_DEVIATION NA • n=10 Participants
NA years
STANDARD_DEVIATION NA • n=115 Participants
40.3 years
STANDARD_DEVIATION 5.3 • n=24 Participants
40.3 years
STANDARD_DEVIATION 5.3 • n=42 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=10 Participants
0 Participants
n=115 Participants
0 Participants
n=24 Participants
0 Participants
n=42 Participants
Sex: Female, Male
Male
18 Participants
n=5 Participants
15 Participants
n=7 Participants
9 Participants
n=5 Participants
9 Participants
n=4 Participants
9 Participants
n=21 Participants
9 Participants
n=10 Participants
9 Participants
n=115 Participants
21 Participants
n=24 Participants
99 Participants
n=42 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=10 Participants
0 Participants
n=115 Participants
0 Participants
n=24 Participants
0 Participants
n=42 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
18 Participants
n=5 Participants
15 Participants
n=7 Participants
9 Participants
n=5 Participants
9 Participants
n=4 Participants
9 Participants
n=21 Participants
9 Participants
n=10 Participants
9 Participants
n=115 Participants
21 Participants
n=24 Participants
99 Participants
n=42 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=10 Participants
0 Participants
n=115 Participants
0 Participants
n=24 Participants
0 Participants
n=42 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=10 Participants
0 Participants
n=115 Participants
0 Participants
n=24 Participants
0 Participants
n=42 Participants
Race (NIH/OMB)
Asian
18 Participants
n=5 Participants
14 Participants
n=7 Participants
9 Participants
n=5 Participants
8 Participants
n=4 Participants
9 Participants
n=21 Participants
8 Participants
n=10 Participants
9 Participants
n=115 Participants
21 Participants
n=24 Participants
96 Participants
n=42 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
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=10 Participants
0 Participants
n=115 Participants
0 Participants
n=24 Participants
0 Participants
n=42 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=10 Participants
0 Participants
n=115 Participants
0 Participants
n=24 Participants
0 Participants
n=42 Participants
Race (NIH/OMB)
White
0 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
0 Participants
n=21 Participants
1 Participants
n=10 Participants
0 Participants
n=115 Participants
0 Participants
n=24 Participants
3 Participants
n=42 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=10 Participants
0 Participants
n=115 Participants
0 Participants
n=24 Participants
0 Participants
n=42 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=10 Participants
0 Participants
n=115 Participants
0 Participants
n=24 Participants
0 Participants
n=42 Participants
Region of Enrollment
Singapore
18 Participants
n=5 Participants
15 Participants
n=7 Participants
9 Participants
n=5 Participants
9 Participants
n=4 Participants
9 Participants
n=21 Participants
9 Participants
n=10 Participants
9 Participants
n=115 Participants
21 Participants
n=24 Participants
99 Participants
n=42 Participants

PRIMARY outcome

Timeframe: Baseline Through End of Study (up to Week 7)

Population: All participants who received at least one dose of study drug.

A summary of other nonserious adverse events (AEs) and all SAEs, regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure
Cohort 1 - Placebo
n=9 Participants
Placebo administered once, PO.
Cohort 1 - 2 mg LY2969822
n=6 Participants
20 mg LY2969822 administered once, PO.
Cohort 1 - 20 mg LY2969822
n=6 Participants
20 mg LY2969822 administered once, PO.
Cohort 1 - 40 mg LY2969822
n=5 Participants
40 mg LY2969822 administered once, PO.
Cohort 2 - Placebo
n=9 Participants
Placebo administered once, PO.
Cohort 2 - 6 mg LY2969822
n=6 Participants
6 mg LY2969822 administered once, PO.
Cohort 2 - 60 mg LY2969822
n=6 Participants
60 mg LY2969822 administered once, PO.
Cohort 2 - 20 mg LY2969822
n=6 Participants
20 mg LY2969822 administered once, PO.
Cohorts 3-7 - Placebo
n=15 Participants
Placebo administered QD or BID, PO, for 14 days.
Cohort 3 - 20 mg LY2969822 QD
n=9 Participants
20 mg LY2969822 administered QD, PO, for 14 days.
Cohort 4 - 40 mg LY2969822 QD Titrated
n=9 Participants
Up to 40 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 3 days, 20 mg QD for 2 days, and 40 mg QD for 9 days.
Cohort 5 - 80 mg LY2969822 QD Titrated
n=9 Participants
Up to 80 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 2 days, 20 mg QD for 2 days, 40 mg QD for 2 days and 80 mg QD for 8 days.
Cohort 6 - 80 mg LY2969822 BID Titrated
n=9 Participants
Up to 80 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.
Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated
n=9 Participants
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, and 40 mg BID for 12 days.
Cohort 8 - Placebo BID
n=10 Participants
Placebo administered BID, PO, for 14 days.
Cohort 8A - 40 mg LY2969822 BID Titrated
n=4 Participants
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.)
Cohort 8B - 20 mg LY2969822 BID Titrated
n=7 Participants
Up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, and 20 mg BID for 10 days.
Cohort 8A - 6 mg LY2969822 BID Day 1
6 mg up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.
Cohort 8A - 40 mg BID LY2969822 Day 14
6 mg up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.
Cohort 8B - 6 mg LY2969822 BID Day 1
6 mg up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 10 days.
Cohort 8B - 20 mg BID LY2969822 Day 14
6 mg up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 10 days.
Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
0 participants
—
—
—
—

SECONDARY outcome

Timeframe: All Cohorts: Day 1 - 0 Hours (H), 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohort 3: Day 10 - 0 H, 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohorts 3 - 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H

Population: All participants who received at least one dose of LY2969822 and had evaluable plasma values.

Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747

Outcome measures

Outcome measures
Measure
Cohort 1 - Placebo
n=6 Participants
Placebo administered once, PO.
Cohort 1 - 2 mg LY2969822
n=6 Participants
20 mg LY2969822 administered once, PO.
Cohort 1 - 20 mg LY2969822
n=5 Participants
20 mg LY2969822 administered once, PO.
Cohort 1 - 40 mg LY2969822
n=6 Participants
40 mg LY2969822 administered once, PO.
Cohort 2 - Placebo
n=6 Participants
Placebo administered once, PO.
Cohort 2 - 6 mg LY2969822
n=6 Participants
6 mg LY2969822 administered once, PO.
Cohort 2 - 60 mg LY2969822
n=9 Participants
60 mg LY2969822 administered once, PO.
Cohort 2 - 20 mg LY2969822
n=8 Participants
20 mg LY2969822 administered once, PO.
Cohorts 3-7 - Placebo
n=9 Participants
Placebo administered QD or BID, PO, for 14 days.
Cohort 3 - 20 mg LY2969822 QD
n=9 Participants
20 mg LY2969822 administered QD, PO, for 14 days.
Cohort 4 - 40 mg LY2969822 QD Titrated
n=8 Participants
Up to 40 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 3 days, 20 mg QD for 2 days, and 40 mg QD for 9 days.
Cohort 5 - 80 mg LY2969822 QD Titrated
n=9 Participants
Up to 80 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 2 days, 20 mg QD for 2 days, 40 mg QD for 2 days and 80 mg QD for 8 days.
Cohort 6 - 80 mg LY2969822 BID Titrated
n=8 Participants
Up to 80 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.
Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated
n=9 Participants
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, and 40 mg BID for 12 days.
Cohort 8 - Placebo BID
n=8 Participants
Placebo administered BID, PO, for 14 days.
Cohort 8A - 40 mg LY2969822 BID Titrated
n=9 Participants
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.)
Cohort 8B - 20 mg LY2969822 BID Titrated
n=5 Participants
Up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, and 20 mg BID for 10 days.
Cohort 8A - 6 mg LY2969822 BID Day 1
n=4 Participants
6 mg up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.
Cohort 8A - 40 mg BID LY2969822 Day 14
n=1 Participants
6 mg up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.
Cohort 8B - 6 mg LY2969822 BID Day 1
n=7 Participants
6 mg up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 10 days.
Cohort 8B - 20 mg BID LY2969822 Day 14
n=6 Participants
6 mg up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 10 days.
Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747
LY2969822
19.9 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 28
209 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 20
346 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 21
63.3 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 33
646 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 31
197 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 22
192 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 47
216 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 33
341 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 33
51.3 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 67
340 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 35
60.2 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 28
771 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 51
49.8 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 34
788 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 30
85.9 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 43
539 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 35
61.3 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 59
NA nanomoles per liter (nmol/L)
Geometric Coefficient of Variation NA
n=1. Individual value is 467.45 nmol/L.
44.9 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 35
216 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 32
Pharmacokinetics (PK): Maximum Plasma Concentration (Plasma Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747
LSN2934747
108 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 21
978 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 10
1700 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 19
289 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 43
2850 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 18
840 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 20
847 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 30
1200 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 18
1520 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 14
232 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 35
1600 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 20
332 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 31
4190 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 28
303 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 35
4130 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 14
461 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 50
2390 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 17
381 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 21
NA nanomoles per liter (nmol/L)
Geometric Coefficient of Variation NA
n=1. Individual value is 2777.08 nmol/L.
263 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 29
1150 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 14

SECONDARY outcome

Timeframe: Cohort 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H

Population: CSF samples were only collected in Cohort 8. All participants in Cohort 8 who received at least one dose of LY2969822 and had evaluable CSF values on Day 14.

PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747

Outcome measures

Outcome measures
Measure
Cohort 1 - Placebo
n=1 Participants
Placebo administered once, PO.
Cohort 1 - 2 mg LY2969822
n=6 Participants
20 mg LY2969822 administered once, PO.
Cohort 1 - 20 mg LY2969822
20 mg LY2969822 administered once, PO.
Cohort 1 - 40 mg LY2969822
40 mg LY2969822 administered once, PO.
Cohort 2 - Placebo
Placebo administered once, PO.
Cohort 2 - 6 mg LY2969822
6 mg LY2969822 administered once, PO.
Cohort 2 - 60 mg LY2969822
60 mg LY2969822 administered once, PO.
Cohort 2 - 20 mg LY2969822
20 mg LY2969822 administered once, PO.
Cohorts 3-7 - Placebo
Placebo administered QD or BID, PO, for 14 days.
Cohort 3 - 20 mg LY2969822 QD
20 mg LY2969822 administered QD, PO, for 14 days.
Cohort 4 - 40 mg LY2969822 QD Titrated
Up to 40 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 3 days, 20 mg QD for 2 days, and 40 mg QD for 9 days.
Cohort 5 - 80 mg LY2969822 QD Titrated
Up to 80 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 2 days, 20 mg QD for 2 days, 40 mg QD for 2 days and 80 mg QD for 8 days.
Cohort 6 - 80 mg LY2969822 BID Titrated
Up to 80 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.
Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, and 40 mg BID for 12 days.
Cohort 8 - Placebo BID
Placebo administered BID, PO, for 14 days.
Cohort 8A - 40 mg LY2969822 BID Titrated
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.)
Cohort 8B - 20 mg LY2969822 BID Titrated
Up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, and 20 mg BID for 10 days.
Cohort 8A - 6 mg LY2969822 BID Day 1
6 mg up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.
Cohort 8A - 40 mg BID LY2969822 Day 14
6 mg up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.
Cohort 8B - 6 mg LY2969822 BID Day 1
6 mg up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 10 days.
Cohort 8B - 20 mg BID LY2969822 Day 14
6 mg up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 10 days.
PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747
LY2969822
NA nmol/L
Geometric Coefficient of Variation NA
n=1. Individual value is 9.86 nmol/L.
8.42 nmol/L
Geometric Coefficient of Variation 106
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
PK: Maximum Cerebrospinal Fluid Concentrations (CSF Cmax) of Prodrug LY2969822 and Active Metabolite LSN2934747
LSN2934747
NA nmol/L
Geometric Coefficient of Variation NA
n=1. Individual value is 149 nmol/L.
93.0 nmol/L
Geometric Coefficient of Variation 59
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—

SECONDARY outcome

Timeframe: All Cohorts: Day 1 - 0 Hours (H), 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohort 3: Day 10 - 0 H, 0.5 H, 1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H; Cohorts 3 - 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H

Population: All participants who received at least one dose of LY2969822 and had evaluable plasma values.

For Cohorts 1-2, AUC is extrapolated from time zero to infinity (AUC\[0-inf\]). For Cohorts 3 - 8, AUC is reported during one dosing interval (AUC\[tau\]). AUC(tau) is 24 hours for Cohorts 3 - 5 and 12 hours for Cohorts 6 - 8.

Outcome measures

Outcome measures
Measure
Cohort 1 - Placebo
n=6 Participants
Placebo administered once, PO.
Cohort 1 - 2 mg LY2969822
n=6 Participants
20 mg LY2969822 administered once, PO.
Cohort 1 - 20 mg LY2969822
n=5 Participants
20 mg LY2969822 administered once, PO.
Cohort 1 - 40 mg LY2969822
n=6 Participants
40 mg LY2969822 administered once, PO.
Cohort 2 - Placebo
n=6 Participants
Placebo administered once, PO.
Cohort 2 - 6 mg LY2969822
n=6 Participants
6 mg LY2969822 administered once, PO.
Cohort 2 - 60 mg LY2969822
n=9 Participants
60 mg LY2969822 administered once, PO.
Cohort 2 - 20 mg LY2969822
n=8 Participants
20 mg LY2969822 administered once, PO.
Cohorts 3-7 - Placebo
n=9 Participants
Placebo administered QD or BID, PO, for 14 days.
Cohort 3 - 20 mg LY2969822 QD
n=9 Participants
20 mg LY2969822 administered QD, PO, for 14 days.
Cohort 4 - 40 mg LY2969822 QD Titrated
n=8 Participants
Up to 40 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 3 days, 20 mg QD for 2 days, and 40 mg QD for 9 days.
Cohort 5 - 80 mg LY2969822 QD Titrated
n=9 Participants
Up to 80 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 2 days, 20 mg QD for 2 days, 40 mg QD for 2 days and 80 mg QD for 8 days.
Cohort 6 - 80 mg LY2969822 BID Titrated
n=8 Participants
Up to 80 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.
Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated
n=9 Participants
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, and 40 mg BID for 12 days.
Cohort 8 - Placebo BID
n=8 Participants
Placebo administered BID, PO, for 14 days.
Cohort 8A - 40 mg LY2969822 BID Titrated
n=9 Participants
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.)
Cohort 8B - 20 mg LY2969822 BID Titrated
n=5 Participants
Up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, and 20 mg BID for 10 days.
Cohort 8A - 6 mg LY2969822 BID Day 1
n=4 Participants
6 mg up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.
Cohort 8A - 40 mg BID LY2969822 Day 14
n=1 Participants
6 mg up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.
Cohort 8B - 6 mg LY2969822 BID Day 1
n=7 Participants
6 mg up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 10 days.
Cohort 8B - 20 mg BID LY2969822 Day 14
n=6 Participants
6 mg up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 10 days.
PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747
LY2969822
88.5 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 22
843 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 19
1730 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 12
273 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 36
3700 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 26
1110 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 38
759 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 50
896 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 27
1160 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 25
231 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 51
1400 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 42
244 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 36
3430 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 55
203 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 42
2810 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 35
363 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 46
1820 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 40
306 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 65
NA nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation NA
n=1. Individual value is 1840 nmol∙h/L.
207 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 44
778 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 34
PK: Area Under the Drug Plasma Concentration Time Curve (Plasma AUC) of Prodrug LY2969822 and Active Metabolite LSN2934747
LSN2934747
805 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 18
7030 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 12
13500 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 25
2090 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 39
23600 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 17
6970 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 22
5830 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 36
8220 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 15
8660 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 12
1710 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 28
10600 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 28
2100 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 26
29000 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 30
1810 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 30
25300 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 18
3010 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 49
14400 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 19
2670 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 20
NA nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation NA
n=1. Individual value is 15800 nmol∙h/L.
1790 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 20
6920 nanomoles x hours per liter (nmol∙h/L)
Geometric Coefficient of Variation 18

SECONDARY outcome

Timeframe: Cohort 8: Day 14 - 0 H, 0.5 H,1 H, 2 H, 3 H, 4 H, 6 H, 9 H, 12 H, 16 H

Population: CSF samples were only collected in Cohort 8. All participants in Cohort 8 who received at least one dose of LY2969822 and had evaluable CSF values on Day 14.

AUC(tau) is 12 hours.

Outcome measures

Outcome measures
Measure
Cohort 1 - Placebo
n=1 Participants
Placebo administered once, PO.
Cohort 1 - 2 mg LY2969822
n=6 Participants
20 mg LY2969822 administered once, PO.
Cohort 1 - 20 mg LY2969822
20 mg LY2969822 administered once, PO.
Cohort 1 - 40 mg LY2969822
40 mg LY2969822 administered once, PO.
Cohort 2 - Placebo
Placebo administered once, PO.
Cohort 2 - 6 mg LY2969822
6 mg LY2969822 administered once, PO.
Cohort 2 - 60 mg LY2969822
60 mg LY2969822 administered once, PO.
Cohort 2 - 20 mg LY2969822
20 mg LY2969822 administered once, PO.
Cohorts 3-7 - Placebo
Placebo administered QD or BID, PO, for 14 days.
Cohort 3 - 20 mg LY2969822 QD
20 mg LY2969822 administered QD, PO, for 14 days.
Cohort 4 - 40 mg LY2969822 QD Titrated
Up to 40 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 3 days, 20 mg QD for 2 days, and 40 mg QD for 9 days.
Cohort 5 - 80 mg LY2969822 QD Titrated
Up to 80 mg LY2969822 administered QD, PO, for 14 days. Titration: 6 mg QD for 2 days, 20 mg QD for 2 days, 40 mg QD for 2 days and 80 mg QD for 8 days.
Cohort 6 - 80 mg LY2969822 BID Titrated
Up to 80 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, 40 mg BID for 2 days, and 80 mg BID for 6 days.
Cohort 7 - 40 mg LY2969822 BID Rapidly Titrated
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 10 mg BID for 1 day, 20 mg BID for 1 day, and 40 mg BID for 12 days.
Cohort 8 - Placebo BID
Placebo administered BID, PO, for 14 days.
Cohort 8A - 40 mg LY2969822 BID Titrated
Up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.)
Cohort 8B - 20 mg LY2969822 BID Titrated
Up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, and 20 mg BID for 10 days.
Cohort 8A - 6 mg LY2969822 BID Day 1
6 mg up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.
Cohort 8A - 40 mg BID LY2969822 Day 14
6 mg up to 40 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 2 days, and 40 mg BID for 8 days.
Cohort 8B - 6 mg LY2969822 BID Day 1
6 mg up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 10 days.
Cohort 8B - 20 mg BID LY2969822 Day 14
6 mg up to 20 mg LY2969822 administered BID, PO, for 14 days. Titration: 6 mg BID for 2 days, 10 mg BID for 2 days, 20 mg BID for 10 days.
PK: CSF AUC(Tau) of Prodrug LY2969822 and Active Metabolite LSN2934747
LY2969822
NA nmol∙h/L
Geometric Coefficient of Variation NA
n=1. Individual value is 1840 nmol∙h/L.
75.1 nmol∙h/L
Geometric Coefficient of Variation 85
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
PK: CSF AUC(Tau) of Prodrug LY2969822 and Active Metabolite LSN2934747
LSN2934747
NA nmol∙h/L
Geometric Coefficient of Variation NA
n=1. Individual value is 15800 nmol∙h/L.
831 nmol∙h/L
Geometric Coefficient of Variation 61
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—

Adverse Events

Part A: Placebo

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Part A: 2 mg LY2969822

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

Part A: 6 mg LY2969822

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Part A: 20 mg LY2969822

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Part A: 40 mg LY2969822

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Part A: 60 mg LY2969822

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

Part B: Placebo

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Part B: Placebo BID

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Part B: 6 mg LY2969822

Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths

Part B: 6 mg LY2969822 BID

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Part B: 10 mg LY2969822 BID

Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths

Part B: 20 mg LY2969822

Serious events: 0 serious events
Other events: 21 other events
Deaths: 0 deaths

Part B: 20 mg LY2969822 BID

Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths

Part B: 40 mg LY2969822

Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths

Part B: 40 mg LY2969822 BID

Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths

Part B: 80 mg LY2969822

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Part B: 80 mg LY2969822 BID

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Part C: Placebo BID

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

Part C: 6 mg LY2969822 BID

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

Part C: 10 mg LY2969822 BID

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

Part C: 20 mg LY2969822 BID

Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths

Part C: 40 mg LY2969822 BID

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Part A: Placebo
n=18 participants at risk
Placebo administered once, PO.
Part A: 2 mg LY2969822
n=6 participants at risk
2 mg LY2969822 administered once, PO.
Part A: 6 mg LY2969822
n=6 participants at risk
6 mg LY2969822 administered once, PO.
Part A: 20 mg LY2969822
n=12 participants at risk
20 mg LY2969822 administered once, PO.
Part A: 40 mg LY2969822
n=5 participants at risk
40 mg LY2969822 administered once, PO.
Part A: 60 mg LY2969822
n=6 participants at risk
60 mg LY2969822 administered once, PO.
Part B: Placebo
n=9 participants at risk
Placebo administered QD, PO, for 14 days.
Part B: Placebo BID
n=6 participants at risk
Placebo administered BID, PO, for 14 days.
Part B: 6 mg LY2969822
n=18 participants at risk
6 mg LY2969822 administered QD, PO, for 2 - 3 days
Part B: 6 mg LY2969822 BID
n=9 participants at risk
6 mg LY2969822 administered BID, PO, for 2 days.
Part B: 10 mg LY2969822 BID
n=18 participants at risk
10 mg LY2969822 administered BID, PO, for 1-2 days.
Part B: 20 mg LY2969822
n=27 participants at risk
20 mg LY2969822 administered QD, PO, for up to 14 days.
Part B: 20 mg LY2969822 BID
n=17 participants at risk
20 mg LY2969822 administered BID, PO, for 1-2 days.
Part B: 40 mg LY2969822
n=18 participants at risk
40 mg LY2969822 administered QD, PO, for up to 9 days.
Part B: 40 mg LY2969822 BID
n=16 participants at risk
40 mg LY2969822 administered BID, PO, for up to 12 days.
Part B: 80 mg LY2969822
n=9 participants at risk
80 mg LY2969822 administered QD, PO, for 8 days.
Part B: 80 mg LY2969822 BID
n=8 participants at risk
80 mg LY2969822 administered BID, PO, for 6 days.
Part C: Placebo BID
n=10 participants at risk
Placebo administered BID, PO, for 14 days.
Part C: 6 mg LY2969822 BID
n=11 participants at risk
6 mg LY2969822 administered BID, PO, for 2 days.
Part C: 10 mg LY2969822 BID
n=11 participants at risk
10 mg LY2969822 administered BID, PO, for 2 days.
Part C: 20 mg LY2969822 BID
n=11 participants at risk
20 mg LY2969822 administered BID, PO, for up to 10 days.
Part C: 40 mg LY2969822 BID
n=4 participants at risk
40 mg LY2969822 administered BID, PO, for up to 8 days.
Investigations
Alanine aminotransferase increased
0.00%
0/18
0.00%
0/6
0.00%
0/6
8.3%
1/12 • Number of events 1
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Investigations
Heart rate increased
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 2
0.00%
0/9
12.5%
1/8 • Number of events 1
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Investigations
Respiratory rate increased
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
5.9%
1/17 • Number of events 1
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Cardiac disorders
Palpitations
0.00%
0/18
0.00%
0/6
0.00%
0/6
8.3%
1/12 • Number of events 1
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
22.2%
2/9 • Number of events 2
25.0%
2/8 • Number of events 2
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Eye disorders
Eye pain
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Eye disorders
Eye pruritus
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Eye disorders
Lacrimation increased
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/4
Eye disorders
Vision blurred
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Abdominal discomfort
5.6%
1/18 • Number of events 1
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
7.4%
2/27 • Number of events 3
0.00%
0/17
0.00%
0/18
0.00%
0/16
11.1%
1/9 • Number of events 1
0.00%
0/8
10.0%
1/10 • Number of events 1
9.1%
1/11 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Abdominal distension
0.00%
0/18
0.00%
0/6
0.00%
0/6
8.3%
1/12 • Number of events 1
20.0%
1/5 • Number of events 1
16.7%
1/6 • Number of events 1
11.1%
1/9 • Number of events 2
0.00%
0/6
5.6%
1/18 • Number of events 1
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
12.5%
2/16 • Number of events 3
11.1%
1/9 • Number of events 2
12.5%
1/8 • Number of events 1
10.0%
1/10 • Number of events 1
9.1%
1/11 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Abdominal pain upper
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
20.0%
1/5 • Number of events 2
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
11.1%
3/27 • Number of events 5
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 2
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Abnormal faeces
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
5.6%
1/18 • Number of events 1
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
11.1%
1/9 • Number of events 1
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Diarrhoea
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
20.0%
1/5 • Number of events 1
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
7.4%
2/27 • Number of events 3
0.00%
0/17
5.6%
1/18 • Number of events 1
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Dyspepsia
5.6%
1/18 • Number of events 1
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
16.7%
1/6 • Number of events 1
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
5.6%
1/18 • Number of events 1
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
11.1%
1/9 • Number of events 1
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Faeces discoloured
5.6%
1/18 • Number of events 1
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
66.7%
4/6 • Number of events 36
11.1%
2/18 • Number of events 2
44.4%
4/9 • Number of events 5
33.3%
6/18 • Number of events 12
7.4%
2/27 • Number of events 2
41.2%
7/17 • Number of events 9
11.1%
2/18 • Number of events 2
37.5%
6/16 • Number of events 10
22.2%
2/9 • Number of events 2
62.5%
5/8 • Number of events 16
70.0%
7/10 • Number of events 23
45.5%
5/11 • Number of events 7
90.9%
10/11 • Number of events 13
72.7%
8/11 • Number of events 13
100.0%
4/4 • Number of events 8
Gastrointestinal disorders
Faeces hard
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 2
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Flatulence
5.6%
1/18 • Number of events 1
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
5.6%
1/18 • Number of events 1
0.00%
0/27
0.00%
0/17
11.1%
2/18 • Number of events 2
0.00%
0/16
11.1%
1/9 • Number of events 1
12.5%
1/8 • Number of events 1
10.0%
1/10 • Number of events 1
18.2%
2/11 • Number of events 2
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Haematochezia
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Mouth ulceration
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
5.6%
1/18 • Number of events 1
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Nausea
0.00%
0/18
0.00%
0/6
33.3%
2/6 • Number of events 2
33.3%
4/12 • Number of events 4
40.0%
2/5 • Number of events 2
66.7%
4/6 • Number of events 4
11.1%
1/9 • Number of events 3
16.7%
1/6 • Number of events 2
50.0%
9/18 • Number of events 16
44.4%
4/9 • Number of events 4
38.9%
7/18 • Number of events 8
33.3%
9/27 • Number of events 15
17.6%
3/17 • Number of events 5
33.3%
6/18 • Number of events 9
25.0%
4/16 • Number of events 5
33.3%
3/9 • Number of events 3
0.00%
0/8
20.0%
2/10 • Number of events 5
36.4%
4/11 • Number of events 4
0.00%
0/11
0.00%
0/11
25.0%
1/4 • Number of events 1
Gastrointestinal disorders
Parotid gland enlargement
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Gastrointestinal disorders
Vomiting
0.00%
0/18
0.00%
0/6
16.7%
1/6 • Number of events 1
16.7%
2/12 • Number of events 3
20.0%
1/5 • Number of events 1
100.0%
6/6 • Number of events 27
0.00%
0/9
0.00%
0/6
22.2%
4/18 • Number of events 12
22.2%
2/9 • Number of events 3
22.2%
4/18 • Number of events 20
29.6%
8/27 • Number of events 33
11.8%
2/17 • Number of events 5
27.8%
5/18 • Number of events 25
18.8%
3/16 • Number of events 12
33.3%
3/9 • Number of events 8
12.5%
1/8 • Number of events 4
20.0%
2/10 • Number of events 6
27.3%
3/11 • Number of events 5
0.00%
0/11
9.1%
1/11 • Number of events 3
25.0%
1/4 • Number of events 1
General disorders
Application site pruritus
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
16.7%
1/6 • Number of events 1
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Catheter site pain
5.6%
1/18 • Number of events 1
16.7%
1/6 • Number of events 1
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
22.2%
2/9 • Number of events 3
50.0%
3/6 • Number of events 4
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
5.9%
1/17 • Number of events 1
0.00%
0/18
12.5%
2/16 • Number of events 2
0.00%
0/9
12.5%
1/8 • Number of events 1
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
25.0%
1/4 • Number of events 1
General disorders
Catheter site related reaction
5.6%
1/18 • Number of events 1
33.3%
2/6 • Number of events 2
16.7%
1/6 • Number of events 1
0.00%
0/12
0.00%
0/5
0.00%
0/6
77.8%
7/9 • Number of events 11
50.0%
3/6 • Number of events 7
5.6%
1/18 • Number of events 1
0.00%
0/9
11.1%
2/18 • Number of events 3
3.7%
1/27 • Number of events 1
5.9%
1/17 • Number of events 1
22.2%
4/18 • Number of events 8
37.5%
6/16 • Number of events 9
11.1%
1/9 • Number of events 1
25.0%
2/8 • Number of events 2
30.0%
3/10 • Number of events 6
0.00%
0/11
18.2%
2/11 • Number of events 2
18.2%
2/11 • Number of events 2
50.0%
2/4 • Number of events 2
General disorders
Chest discomfort
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 2
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Facial pain
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Feeling abnormal
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
11.1%
1/9 • Number of events 1
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
7.4%
2/27 • Number of events 4
5.9%
1/17 • Number of events 1
11.1%
2/18 • Number of events 2
0.00%
0/16
11.1%
1/9 • Number of events 2
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Feeling cold
0.00%
0/18
0.00%
0/6
16.7%
1/6 • Number of events 1
8.3%
1/12 • Number of events 1
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
5.6%
1/18 • Number of events 1
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Feeling hot
0.00%
0/18
0.00%
0/6
0.00%
0/6
8.3%
1/12 • Number of events 1
20.0%
1/5 • Number of events 1
0.00%
0/6
0.00%
0/9
16.7%
1/6 • Number of events 1
0.00%
0/18
0.00%
0/9
0.00%
0/18
7.4%
2/27 • Number of events 2
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Gait disturbance
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
5.6%
1/18 • Number of events 1
18.5%
5/27 • Number of events 5
5.9%
1/17 • Number of events 1
16.7%
3/18 • Number of events 3
6.2%
1/16 • Number of events 1
33.3%
3/9 • Number of events 3
0.00%
0/8
0.00%
0/10
9.1%
1/11 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Hunger
5.6%
1/18 • Number of events 1
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
11.1%
1/9 • Number of events 1
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Injection site erythema
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
5.6%
1/18 • Number of events 1
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Non-cardiac chest pain
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
16.7%
1/6 • Number of events 1
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Puncture site pain
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/4
General disorders
Pyrexia
0.00%
0/18
0.00%
0/6
0.00%
0/6
8.3%
1/12 • Number of events 1
20.0%
1/5 • Number of events 1
16.7%
1/6 • Number of events 1
22.2%
2/9 • Number of events 2
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
7.4%
2/27 • Number of events 2
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
12.5%
1/8 • Number of events 1
0.00%
0/10
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
25.0%
1/4 • Number of events 1
General disorders
Vessel puncture site bruise
0.00%
0/18
16.7%
1/6 • Number of events 1
16.7%
1/6 • Number of events 1
25.0%
3/12 • Number of events 3
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/4
General disorders
Vessel puncture site pain
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Vessel puncture site reaction
0.00%
0/18
0.00%
0/6
0.00%
0/6
8.3%
1/12 • Number of events 1
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
General disorders
Vessel puncture site swelling
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Infections and infestations
Influenza
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
16.7%
1/6 • Number of events 1
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Injury, poisoning and procedural complications
Accident at work
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
20.0%
1/5 • Number of events 1
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Injury, poisoning and procedural complications
Arthropod sting
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Injury, poisoning and procedural complications
Contusion
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
25.0%
1/4 • Number of events 1
Injury, poisoning and procedural complications
Excoriation
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
25.0%
1/4 • Number of events 2
Injury, poisoning and procedural complications
Fall
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
12.5%
1/8 • Number of events 1
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Injury, poisoning and procedural complications
Injury
0.00%
0/18
0.00%
0/6
0.00%
0/6
8.3%
1/12 • Number of events 1
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Injury, poisoning and procedural complications
Muscle strain
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
5.6%
1/18 • Number of events 1
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Injury, poisoning and procedural complications
Procedural site reaction
5.6%
1/18 • Number of events 1
0.00%
0/6
16.7%
1/6 • Number of events 1
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
33.3%
2/6 • Number of events 2
0.00%
0/18
0.00%
0/9
5.6%
1/18 • Number of events 1
3.7%
1/27 • Number of events 1
0.00%
0/17
5.6%
1/18 • Number of events 1
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
18.2%
2/11 • Number of events 3
25.0%
1/4 • Number of events 4
Injury, poisoning and procedural complications
Scratch
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
5.6%
1/18 • Number of events 1
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Metabolism and nutrition disorders
Decreased appetite
0.00%
0/18
0.00%
0/6
16.7%
1/6 • Number of events 1
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
12.5%
1/8 • Number of events 1
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Musculoskeletal and connective tissue disorders
Arthralgia
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
3.7%
1/27 • Number of events 1
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
16.7%
1/6 • Number of events 2
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
30.0%
3/10 • Number of events 3
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/4
Musculoskeletal and connective tissue disorders
Muscle spasms
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Musculoskeletal and connective tissue disorders
Muscle tightness
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Musculoskeletal and connective tissue disorders
Muscle twitching
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
11.1%
1/9 • Number of events 1
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/4
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/4
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
5.9%
1/17 • Number of events 1
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
27.3%
3/11 • Number of events 3
0.00%
0/4
Musculoskeletal and connective tissue disorders
Neck pain
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/4
Musculoskeletal and connective tissue disorders
Pain in extremity
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Musculoskeletal and connective tissue disorders
Sensation of heaviness
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
5.9%
1/17 • Number of events 1
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Nervous system disorders
Amnesia
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
11.1%
2/18 • Number of events 3
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Nervous system disorders
Balance disorder
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
5.6%
1/18 • Number of events 1
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Nervous system disorders
Cognitive disorder
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
5.6%
1/18 • Number of events 1
0.00%
0/27
5.9%
1/17 • Number of events 1
5.6%
1/18 • Number of events 1
18.8%
3/16 • Number of events 3
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/11
0.00%
0/4
Nervous system disorders
Dizziness
0.00%
0/18
0.00%
0/6
0.00%
0/6
33.3%
4/12 • Number of events 5
80.0%
4/5 • Number of events 4
33.3%
2/6 • Number of events 2
11.1%
1/9 • Number of events 1
33.3%
2/6 • Number of events 3
22.2%
4/18 • Number of events 5
33.3%
3/9 • Number of events 4
33.3%
6/18 • Number of events 6
37.0%
10/27 • Number of events 20
29.4%
5/17 • Number of events 7
22.2%
4/18 • Number of events 6
50.0%
8/16 • Number of events 12
33.3%
3/9 • Number of events 5
25.0%
2/8 • Number of events 4
10.0%
1/10 • Number of events 1
18.2%
2/11 • Number of events 2
0.00%
0/11
18.2%
2/11 • Number of events 4
25.0%
1/4 • Number of events 1
Nervous system disorders
Dizziness postural
0.00%
0/18
0.00%
0/6
0.00%
0/6
8.3%
1/12 • Number of events 1
0.00%
0/5
50.0%
3/6 • Number of events 5
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
3.7%
1/27 • Number of events 2
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Nervous system disorders
Head discomfort
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
5.6%
1/18 • Number of events 1
0.00%
0/27
41.2%
7/17 • Number of events 7
0.00%
0/18
12.5%
2/16 • Number of events 3
11.1%
1/9 • Number of events 1
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Nervous system disorders
Headache
5.6%
1/18 • Number of events 1
0.00%
0/6
16.7%
1/6 • Number of events 1
8.3%
1/12 • Number of events 1
0.00%
0/5
0.00%
0/6
33.3%
3/9 • Number of events 11
16.7%
1/6 • Number of events 4
11.1%
2/18 • Number of events 3
11.1%
1/9 • Number of events 1
5.6%
1/18 • Number of events 1
25.9%
7/27 • Number of events 13
5.9%
1/17 • Number of events 2
27.8%
5/18 • Number of events 6
37.5%
6/16 • Number of events 11
22.2%
2/9 • Number of events 3
37.5%
3/8 • Number of events 3
50.0%
5/10 • Number of events 7
18.2%
2/11 • Number of events 2
0.00%
0/11
36.4%
4/11 • Number of events 7
50.0%
2/4 • Number of events 2
Nervous system disorders
Hypoaesthesia
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
11.1%
1/9 • Number of events 1
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Nervous system disorders
Lethargy
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
3.7%
1/27 • Number of events 1
0.00%
0/17
0.00%
0/18
0.00%
0/16
11.1%
1/9 • Number of events 1
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Nervous system disorders
Memory impairment
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
3.7%
1/27 • Number of events 1
5.9%
1/17 • Number of events 1
0.00%
0/18
12.5%
2/16 • Number of events 2
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Nervous system disorders
Movement disorder
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
5.6%
1/18 • Number of events 1
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Nervous system disorders
Sleep paralysis
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 2
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Nervous system disorders
Somnolence
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
11.1%
1/9 • Number of events 1
16.7%
1/6 • Number of events 1
0.00%
0/18
0.00%
0/9
0.00%
0/18
7.4%
2/27 • Number of events 2
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
12.5%
1/8 • Number of events 1
0.00%
0/10
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/11
25.0%
1/4 • Number of events 1
Nervous system disorders
Tension headache
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/4
Nervous system disorders
Tremor
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Psychiatric disorders
Emotional disorder
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
5.6%
1/18 • Number of events 1
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Psychiatric disorders
Euphoric mood
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
3.7%
1/27 • Number of events 1
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
18.2%
2/11 • Number of events 2
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/4
Psychiatric disorders
Insomnia
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
5.6%
1/18 • Number of events 2
6.2%
1/16 • Number of events 1
11.1%
1/9 • Number of events 1
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
25.0%
1/4 • Number of events 1
Psychiatric disorders
Panic attack
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Psychiatric disorders
Restlessness
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
3.7%
1/27 • Number of events 1
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Psychiatric disorders
Sleep disorder
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
11.1%
1/9 • Number of events 1
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Renal and urinary disorders
Chromaturia
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
9.1%
1/11 • Number of events 1
0.00%
0/11
0.00%
0/4
Renal and urinary disorders
Urinary hesitation
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Cough
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
22.2%
2/9 • Number of events 2
16.7%
1/6 • Number of events 1
0.00%
0/18
0.00%
0/9
0.00%
0/18
7.4%
2/27 • Number of events 2
0.00%
0/17
5.6%
1/18 • Number of events 1
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
30.0%
3/10 • Number of events 3
0.00%
0/11
0.00%
0/11
18.2%
2/11 • Number of events 3
25.0%
1/4 • Number of events 2
Respiratory, thoracic and mediastinal disorders
Dry throat
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
20.0%
1/5 • Number of events 1
0.00%
0/6
11.1%
1/9 • Number of events 4
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
7.4%
2/27 • Number of events 3
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
5.9%
1/17 • Number of events 1
0.00%
0/18
12.5%
2/16 • Number of events 3
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Hyperventilation
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
5.9%
1/17 • Number of events 1
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Increased upper airway secretion
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
7.4%
2/27 • Number of events 2
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
9.1%
1/11 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Nasal congestion
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
11.1%
1/9 • Number of events 4
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
7.4%
2/27 • Number of events 2
5.9%
1/17 • Number of events 1
0.00%
0/18
6.2%
1/16 • Number of events 1
11.1%
1/9 • Number of events 1
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
27.3%
3/11 • Number of events 3
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
5.6%
1/18 • Number of events 1
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
11.1%
1/9 • Number of events 1
16.7%
1/6 • Number of events 1
0.00%
0/18
0.00%
0/9
0.00%
0/18
3.7%
1/27 • Number of events 1
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
20.0%
2/10 • Number of events 2
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Productive cough
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
11.1%
1/9 • Number of events 1
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
3.7%
1/27 • Number of events 1
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
20.0%
1/5 • Number of events 1
0.00%
0/6
11.1%
1/9 • Number of events 1
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
11.1%
3/27 • Number of events 3
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Skin and subcutaneous tissue disorders
Acne
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
3.7%
1/27 • Number of events 1
0.00%
0/17
5.6%
1/18 • Number of events 1
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Skin and subcutaneous tissue disorders
Cold sweat
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
16.7%
1/6 • Number of events 1
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Skin and subcutaneous tissue disorders
Dermatitis contact
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
10.0%
1/10 • Number of events 1
0.00%
0/11
0.00%
0/11
27.3%
3/11 • Number of events 4
25.0%
1/4 • Number of events 1
Skin and subcutaneous tissue disorders
Erythema
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
16.7%
1/6 • Number of events 2
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
25.0%
1/4 • Number of events 1
Skin and subcutaneous tissue disorders
Hyperhidrosis
0.00%
0/18
0.00%
0/6
0.00%
0/6
8.3%
1/12 • Number of events 1
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
5.6%
1/18 • Number of events 1
0.00%
0/27
0.00%
0/17
0.00%
0/18
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Skin and subcutaneous tissue disorders
Pruritus
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
5.6%
1/18 • Number of events 1
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
25.0%
1/4 • Number of events 1
Skin and subcutaneous tissue disorders
Rash
0.00%
0/18
0.00%
0/6
0.00%
0/6
8.3%
1/12 • Number of events 1
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
3.7%
1/27 • Number of events 2
0.00%
0/17
5.6%
1/18 • Number of events 1
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Vascular disorders
Flushing
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
5.6%
1/18 • Number of events 1
0.00%
0/16
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
0.00%
0/11
0.00%
0/4
Vascular disorders
Hypertension
0.00%
0/18
0.00%
0/6
0.00%
0/6
0.00%
0/12
0.00%
0/5
0.00%
0/6
0.00%
0/9
0.00%
0/6
0.00%
0/18
0.00%
0/9
0.00%
0/18
0.00%
0/27
0.00%
0/17
0.00%
0/18
6.2%
1/16 • Number of events 1
0.00%
0/9
0.00%
0/8
0.00%
0/10
0.00%
0/11
0.00%
0/11
9.1%
1/11 • Number of events 1
50.0%
2/4 • Number of events 2

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