Trial Outcomes & Findings for A Multiple-ascending-dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics (PK) of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus (NCT NCT02548585)

Last Updated: 2019-04-05

Results Overview

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hours (hrs) after consumption of the standardized meal (with no additional food intake during this time).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

113 participants

Primary outcome timeframe

0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post standardized meal intake (SMI) on Baseline (Day -1) and EOT (Day 41)

Results posted on

2019-04-05

Participant Flow

The study was conducted from 09 Dec 2015 to 24 Feb 2017 in Germany.

A total of 422 participants were screened, of which 113 participants were randomized in the study.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo (matched to either 100 micrograms \[mcg\], or 150 mcg or 200 mcg or 300 mcg of MEDI0382) subcutaneously (SC) once daily from Day 1 to Day 7 (Cohort 1); or Day 1 to Day 11 (Cohort 2); or Day 1 to Day 15 (Cohort 3); or Day 1 to Day 41 (Cohort 4); or Day 1 to Day 22 (Cohort 5); or Day 1 to Day 17 (Cohort 6).	Cohort 1: MEDI0382 100 mcg Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.	Cohort 2: MEDI0382 150 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: MEDI0382 200 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 4: MEDI0382 200 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Study STARTED	45	6	6	7	25	12	12
Overall Study Treated	45	6	6	7	25	11	12
Overall Study COMPLETED	43	6	6	5	22	10	11
Overall Study NOT COMPLETED	2	0	0	2	3	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo (matched to either 100 micrograms \[mcg\], or 150 mcg or 200 mcg or 300 mcg of MEDI0382) subcutaneously (SC) once daily from Day 1 to Day 7 (Cohort 1); or Day 1 to Day 11 (Cohort 2); or Day 1 to Day 15 (Cohort 3); or Day 1 to Day 41 (Cohort 4); or Day 1 to Day 22 (Cohort 5); or Day 1 to Day 17 (Cohort 6).	Cohort 3: MEDI0382 200 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 4: MEDI0382 200 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Study Withdrawal by Subject	0	0	0	1	0
Overall Study Lost to Follow-up	1	0	0	0	0
Overall Study Other	1	2	3	0	1
Overall Study Randomized but not treated	0	0	0	1	0

Baseline Characteristics

A Multiple-ascending-dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics (PK) of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=45 Participants Participants received placebo (matched to either 100 micrograms \[mcg\], or 150 mcg or 200 mcg or 300 mcg of MEDI0382) subcutaneously (SC) once daily from Day 1 to Day 7 (Cohort 1); or Day 1 to Day 11 (Cohort 2); or Day 1 to Day 15 (Cohort 3); or Day 1 to Day 41 (Cohort 4); or Day 1 to Day 22 (Cohort 5); or Day 1 to Day 17 (Cohort 6).	Cohort 1: MEDI0382 100 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 4: MEDI0382 200 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 5: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	TOTAL n=112 Participants Total of all reporting groups
Age, Continuous	57.2 Years STANDARD_DEVIATION 6.0 • n=5 Participants	62.5 Years STANDARD_DEVIATION 2.9 • n=7 Participants	60.2 Years STANDARD_DEVIATION 4.2 • n=5 Participants	57.0 Years STANDARD_DEVIATION 4.9 • n=4 Participants	56.0 Years STANDARD_DEVIATION 7.2 • n=21 Participants	54.8 Years STANDARD_DEVIATION 6.8 • n=8 Participants	54.6 Years STANDARD_DEVIATION 6.5 • n=8 Participants	56.9 Years STANDARD_DEVIATION 6.3 • n=24 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	12 Participants n=21 Participants	4 Participants n=8 Participants	3 Participants n=8 Participants	44 Participants n=24 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	13 Participants n=21 Participants	7 Participants n=8 Participants	9 Participants n=8 Participants	68 Participants n=24 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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	25 Participants n=21 Participants	11 Participants n=8 Participants	12 Participants n=8 Participants	112 Participants n=24 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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Asian	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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Black or African American	1 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=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	25 Participants n=21 Participants	11 Participants n=8 Participants	12 Participants n=8 Participants	111 Participants n=24 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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants

PRIMARY outcome

Timeframe: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post standardized meal intake (SMI) on Baseline (Day -1) and EOT (Day 41)

Population: Pharmacodynamic (PD) population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Percent Change From Baseline in Mixed-meal Test (MMT) Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours to the End of Treatment (EOT) (Cohort 4)	-9.24 Percent change Standard Deviation 12.30	-33.81 Percent change Standard Deviation 18.62	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and EOT (Day 42)

Population: Intent-to-treat (ITT) population included all participants who were randomized and received any study drug and analyzed according to the initial randomization.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Change From Baseline in Body Weight to the EOT (Cohort 4)	-1.71 Kilograms (Kg) Standard Deviation 2.10	-3.83 Kilograms (Kg) Standard Deviation 2.09	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 22 for Cohort 5; and Day 17 for Cohort 6)

Population: PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6)	-14.60 Percent change Standard Deviation 5.56	-41.80 Percent change Standard Deviation 11.07	-15.07 Percent change Standard Deviation 13.46	-36.73 Percent change Standard Deviation 10.09	-0.47 Percent change Standard Deviation 15.16	-39.58 Percent change Standard Deviation 5.27	-14.52 Percent change Standard Deviation 8.12	-41.66 Percent change Standard Deviation 9.97	-4.80 Percent change Standard Deviation 3.45	-38.19 Percent change Standard Deviation 12.51	—	—

SECONDARY outcome

Timeframe: Cohort 1: Baseline (Day 1) to EOT (Day 8); Cohort 2: Baseline (Day 1) to EOT (Day 12); Cohort 3: Baseline (Day 1) to EOT (Day 16); Cohort 5: Baseline (Day 1) to EOT (Day 22); Cohort 6: Baseline (Day 1) to EOT (Day 17)

Population: ITT population included all participants who were randomized and received any study drug and analyzed according to the initial randomization. Participants who did not complete the treatment were not included in this analysis.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6)	-1.20 Kg Standard Deviation 0.44	-2.32 Kg Standard Deviation 1.29	-1.00 Kg Standard Deviation 1.13	-1.52 Kg Standard Deviation 0.57	-2.90 Kg Standard Deviation 1.05	-4.63 Kg Standard Deviation 1.98	-0.98 Kg Standard Deviation 2.12	-3.26 Kg Standard Deviation 1.99	-0.94 Kg Standard Deviation 3.09	-2.04 Kg Standard Deviation 1.52	—	—

SECONDARY outcome

Timeframe: Cohort 4: Baseline (Day -2) to EOT (Day 42); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17)

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6)	-0.58 Percent change Standard Deviation 0.30	-0.92 Percent change Standard Deviation 0.41	-0.10 Percent change Standard Deviation 0.29	-0.55 Percent change Standard Deviation 0.35	-0.18 Percent change Standard Deviation 0.19	-0.42 Percent change Standard Deviation 0.27	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cohort 4: Baseline (Day -2) to EOT (Day 41); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17)

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6)	-33.7 micromol/L Standard Deviation 44.6	-67.9 micromol/L Standard Deviation 44.4	-27.8 micromol/L Standard Deviation 25.8	-47.4 micromol/L Standard Deviation 15.7	-48.8 micromol/L Standard Deviation 43.7	-47.5 micromol/L Standard Deviation 55.3	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cohort 1: Baseline (Day-1) to EOT (Day7); Cohort 2: Baseline (Day-1) to EOT (Day11); Cohort 3: Baseline (Day-1) to EOT (Day15); Cohort 4: Baseline (Day-1) to EOT (Day41); Cohort 5: Baseline (Day-1) to EOT (Day22); Cohort 6: Baseline (Day-1) to EOT (Day17)

Population: PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)	-32.44 mg/dL Standard Deviation 17.19	-74.48 mg/dL Standard Deviation 24.59	-49.86 mg/dL Standard Deviation 23.24	-54.06 mg/dL Standard Deviation 19.51	-4.20 mg/dL Standard Deviation 33.73	-63.67 mg/dL Standard Deviation 11.93	-18.52 mg/dL Standard Deviation 18.88	-50.62 mg/dL Standard Deviation 33.61	-32.08 mg/dL Standard Deviation 17.49	-54.42 mg/dL Standard Deviation 19.75	-16.58 mg/dL Standard Deviation 12.45	-55.21 mg/dL Standard Deviation 31.13

SECONDARY outcome

Timeframe: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, 240 minutes, and 24 hrs post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6)

Population: PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Percent Change From Baseline in Glucose Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h) After MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)	-21.80 Percent change Standard Deviation 1.41	-28.34 Percent change Standard Deviation 13.52	0.80 Percent change Standard Deviation 39.55	-29.32 Percent change Standard Deviation 17.24	-13.80 Percent change Standard Deviation 15.95	-27.07 Percent change Standard Deviation 10.82	-1.06 Percent change Standard Deviation 11.47	-13.50 Percent change Standard Deviation 18.19	-4.20 Percent change Standard Deviation 28.58	-34.51 Percent change Standard Deviation 11.25	-10.10 Percent change Standard Deviation 14.69	-26.95 Percent change Standard Deviation 9.45

SECONDARY outcome

Timeframe: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])

Population: As-treated Population (ATP) included all participants who received any study drug and analyzed according to the treatment they actually received.

An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. Serious adverse events (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days).

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TEAEs	2 Participants	6 Participants	3 Participants	5 Participants	3 Participants	7 Participants	23 Participants	22 Participants	4 Participants	10 Participants	2 Participants	10 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TESAEs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])

Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.

TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to vital signs and physical examination abnormalities were reported.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs Blood Pressure increased	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs Blood pressure systolic increased	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs Blood pressure diastolic increased	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs Physical Examinations	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: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])

Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Supraventricular tachycardia	1 Participants	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Tachycardia	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Arrhythmia	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Atrial fibrillation	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Atrioventricular block first degree	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Atrioventricular block second degree	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Electrocardiogram ST segment depression	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Extrasystoles	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Sinus tachycardia	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Supraventricular extrasystoles	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Ventricular extrasystoles	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs Ventricular tachycardia	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])

Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs Chromaturia	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs Lipase increased	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs Hypokalemia	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs C-reactive protein increased	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs Hypoglycemia	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days)

Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.

The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behaviour of participants. Yes/No responses are mapped to C-SSRS to assess whether participant experienced suicidal behaviour and suicidal ideation. Suicidal behaviour questions includes preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation questions includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act (without specific plan), and active suicidal ideation with specific plan and intent. Participants with yes response to any category for suicidal ideation were reported below.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) Day -1	1 Participants	4 Participants	0 Participants	2 Participants	0 Participants	2 Participants	—	—	—	—	—	—
Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) Day 13	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) Day 20	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) Day 27	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) Day 34	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) Day 40	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6) Days 7-14 post last dose of MEDI0382	—	—	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—	—	—	—

SECONDARY outcome

Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) Day -1	2 Participants	2 Participants	0 Participants	1 Participants	0 Participants	1 Participants	—	—	—	—	—	—
Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) Day 13	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) Day 20	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) Day 27	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) Day 34	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) Day 40	0 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—
Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6) Days 7-14 post last dose of MEDI0382	—	—	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cohort (C) 1 (Day [D] 1 and [&] D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose

Population: Pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.

Terminal elimination half Life is the time measured for the plasma concentration of MEDI0382 to decrease by one half.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=6 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=7 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) Day 1	8.5 hr 95% confidence interval (CI) was not reported as only one participant was evaluable for the specified time point.	—	—	—	—	—	—	—	—	—	—	—
Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) Day 5	—	10.3 hr Interval 7.8 to 13.5	—	—	—	—	—	—	—	—	—	—
Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) Day 7	11.7 hr Interval 5.5 to 25.1	—	—	—	—	—	—	—	—	—	—	—
Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) Day 9	—	—	8.3 hr 95% CI was not reported as only one participant was evaluable for the specified time point.	—	—	—	—	—	—	—	—	—
Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) Day 11	—	11.3 hr Interval 5.9 to 21.7	—	—	—	—	—	—	—	—	—	—
Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3) Day 15	—	—	11.3 hr Interval 8.2 to 15.5	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose

Population: PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.

Accumulation ratio was calculated as, Rac obtained from area under the curve from time zero to end of dosing interval (AUC\[0-tau\]) of Nth day divided by AUC(0-tau) of Day 1.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=6 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=7 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) Day 1	NA Ratio Data is not applicable since accumulation ratio, as described by the formula could not be derived for Cohort 1 Day 1.	—	—	—	—	—	—	—	—	—	—	—
Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) Day 5	—	NA Ratio Data is not applicable since accumulation ratio, as described by the formula could not be derived for Cohort 2 Day 5.	—	—	—	—	—	—	—	—	—	—
Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) Day 7	1.3 Ratio Interval 1.1 to 1.5	—	—	—	—	—	—	—	—	—	—	—
Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) Day 9	—	—	NA Ratio Data is not applicable since accumulation ratio, as described by the formula could not be derived for Cohort 3 Day 9.	—	—	—	—	—	—	—	—	—
Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) Day 11	—	1.1 Ratio Interval 0.9 to 1.8	—	—	—	—	—	—	—	—	—	—
Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3) Day 15	—	—	1.3 Ratio Interval 1.1 to 1.5	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose

Population: PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=6 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=7 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=11 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 1	82.21 ng*hr/mL Interval 44.56 to 151.69	—	—	—	—	—	—	—	—	—	—	—
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 5	—	174.58 ng*hr/mL Interval 87.41 to 348.67	—	—	—	—	—	—	—	—	—	—
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 7	107.01 ng*hr/mL Interval 54.1 to 211.64	—	—	—	—	—	—	—	—	—	—	—
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 9	—	—	194.78 ng*hr/mL Interval 146.17 to 259.56	164.05 ng*hr/mL Interval 42.67 to 630.76	—	—	—	—	—	—	—	—
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 11	—	157.31 ng*hr/mL Interval 82.45 to 421.12	—	—	—	275.29 ng*hr/mL Interval 169.33 to 447.48	—	—	—	—	—	—
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 15	—	—	195.40 ng*hr/mL Interval 89.8 to 425.17	—	—	—	—	—	—	—	—	—
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 16	—	—	—	—	261.90 ng*hr/mL Interval 166.58 to 411.74	—	—	—	—	—	—	—
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 17	—	—	—	—	—	246.06 ng*hr/mL Interval 130.34 to 464.51	—	—	—	—	—	—
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 22	—	—	—	—	254.35 ng*hr/mL Interval 196.1 to 329.9	—	—	—	—	—	—	—
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 41	—	—	—	199.10 ng*hr/mL Interval 84.57 to 468.75	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose

Population: PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=6 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=7 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=11 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 1	103.46 ng*hr/mL 95% CI data not applicable as only one participant was evaluable for this time point.	—	—	—	—	—	—	—	—	—	—	—
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 5	—	207.15 ng*hr/mL Interval 11.98 to 3580.41	—	—	—	—	—	—	—	—	—	—
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 7	184.68 ng*hr/mL Interval 107.76 to 316.51	—	—	—	—	—	—	—	—	—	—	—
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 9	—	—	242.60 ng*hr/mL 95% CI data not applicable as only one participant was evaluable for this time point.	238.22 ng*hr/mL Interval 80.99 to 700.67	—	—	—	—	—	—	—	—
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 11	—	215.80 ng*hr/mL Interval 112.9 to 412.47	—	—	—	—	—	—	—	—	—	—
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 15	—	—	271.84 ng*hr/mL Interval 119.33 to 619.24	—	—	—	—	—	—	—	—	—
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 16	—	—	—	—	317.93 ng*hr/mL Interval 182.24 to 554.64	—	—	—	—	—	—	—
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 17	—	—	—	—	—	327.28 ng*hr/mL Interval 249.98 to 428.49	—	—	—	—	—	—
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 22	—	—	—	—	294.60 ng*hr/mL Interval 172.52 to 503.05	—	—	—	—	—	—	—
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 41	—	—	—	262.17 ng*hr/mL Interval 99.79 to 688.77	—	—	—	—	—	—	—	—

SECONDARY outcome

Population: PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=6 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=7 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=11 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 1	4.97 ng/mL Interval 0.33 to 7.41	—	—	—	—	—	—	—	—	—	—	—
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 5	—	9.66 ng/mL Interval 4.68 to 19.95	—	—	—	—	—	—	—	—	—	—
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 7	6.26 ng/mL Interval 3.36 to 11.67	—	—	—	—	—	—	—	—	—	—	—
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 9	—	—	10.57 ng/mL Interval 6.33 to 17.66	11.64 ng/mL Interval 3.16 to 42.94	—	—	—	—	—	—	—	—
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 11	—	9.57 ng/mL Interval 4.63 to 19.79	—	—	—	13.69 ng/mL Interval 5.73 to 32.71	—	—	—	—	—	—
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 15	—	—	10.97 ng/mL Interval 4.62 to 26.06	—	—	—	—	—	—	—	—	—
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 16	—	—	—	—	17.65 ng/mL Interval 8.82 to 35.29	—	—	—	—	—	—	—
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 17	—	—	—	—	—	15.55 ng/mL Interval 7.55 to 32.01	—	—	—	—	—	—
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 22	—	—	—	—	15.77 ng/mL Interval 10.02 to 24.8	—	—	—	—	—	—	—
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 41	—	—	—	13.42 ng/mL Interval 4.77 to 37.75	—	—	—	—	—	—	—	—

SECONDARY outcome

Population: PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=6 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=7 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=11 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 1	0.705 ng/mL Interval 0.33 to 1.49	—	—	—	—	—	—	—	—	—	—	—
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 5	—	2.685 ng/mL Interval 1.06 to 6.79	—	—	—	—	—	—	—	—	—	—
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 7	2.372 ng/mL Interval 1.18 to 4.78	—	—	—	—	—	—	—	—	—	—	—
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 9	—	—	3.521 ng/mL Interval 2.16 to 5.75	2.635 ng/mL Interval 0.79 to 8.83	—	—	—	—	—	—	—	—
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 11	—	3.59 ng/mL Interval 1.62 to 7.94	—	—	—	3.586 ng/mL Interval 1.45 to 8.88	—	—	—	—	—	—
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 15	—	—	4.973 ng/mL Interval 2.24 to 11.05	—	—	—	—	—	—	—	—	—
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 16	—	—	—	—	4.062 ng/mL Interval 1.68 to 9.84	—	—	—	—	—	—	—
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 17	—	—	—	—	—	4.766 ng/mL Interval 2.74 to 8.3	—	—	—	—	—	—
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 22	—	—	—	—	5.21 ng/mL Interval 1.97 to 13.81	—	—	—	—	—	—	—
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 41	—	—	—	3.38 ng/mL Interval 1.03 to 11.04	—	—	—	—	—	—	—	—

SECONDARY outcome

Population: PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=6 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=7 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=11 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 1	8 hr Interval 6.0 to 8.0	—	—	—	—	—	—	—	—	—	—	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 5	—	6 hr Interval 4.0 to 8.0	—	—	—	—	—	—	—	—	—	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 7	6 hr Interval 4.0 to 6.0	—	—	—	—	—	—	—	—	—	—	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 9	—	—	6 hr Interval 6.0 to 8.0	4 hr Interval 1.0 to 6.0	—	—	—	—	—	—	—	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 11	—	6 hr Interval 4.0 to 6.0	—	—	—	6 hr Interval 4.0 to 12.0	—	—	—	—	—	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 15	—	—	6 hr Interval 4.0 to 8.0	—	—	—	—	—	—	—	—	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 16	—	—	—	—	4 hr Interval 2.0 to 8.0	—	—	—	—	—	—	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 17	—	—	—	—	—	4 hr Interval 2.0 to 6.0	—	—	—	—	—	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 22	—	—	—	—	4 hr Interval 4.0 to 8.0	—	—	—	—	—	—	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6) Day 41	—	—	—	4 hr Interval 4.0 to 8.0	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 up to 7-14 days post-last dose of MEDI0382 for all cohorts (Approximately 60 days)

Population: ATP included all participants who received any study drug and analyzed according to the treatment they actually received.

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6)

Population: PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=11 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo n=5 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6)	10.83 Percent change Standard Deviation 21.33	-9.37 Percent change Standard Deviation 29.17	-3.67 Percent change Standard Deviation 13.76	36.32 Percent change Standard Deviation 35.21	-20.43 Percent change Standard Deviation 68.82	-17.47 Percent change Standard Deviation 38.84	-8.63 Percent change Standard Deviation 32.33	-1.17 Percent change Standard Deviation 44.20	-17.70 Percent change Standard Deviation 16.47	1.01 Percent change Standard Deviation 31.00	-8.18 Percent change Standard Deviation 28.34	-7.72 Percent change Standard Deviation 37.03

SECONDARY outcome

Population: PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)	-3.27 Percent change Standard Deviation 38.92	-52.10 Percent change Standard Deviation 36.29	-33.13 Percent change Standard Deviation 40.07	-36.77 Percent change Standard Deviation 19.62	81.27 Percent change Standard Deviation 77.21	-54.13 Percent change Standard Deviation 26.40	-29.72 Percent change Standard Deviation 31.13	-47.93 Percent change Standard Deviation 22.12	—	—	—	—

SECONDARY outcome

Population: PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)	10.17 Percent change Standard Deviation 5.05	-3.82 Percent change Standard Deviation 21.29	-1.43 Percent change Standard Deviation 6.02	39.78 Percent change Standard Deviation 32.88	79.37 Percent change Standard Deviation 91.56	-9.07 Percent change Standard Deviation 27.27	8.08 Percent change Standard Deviation 32.12	15.66 Percent change Standard Deviation 42.35	—	—	—	—

SECONDARY outcome

Population: PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.

Mixes-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). Incretins included glucagon-like peptide-1 (GLP-1; active and inactive both), glucagon, and gastric inhibitory peptide (GIP).

Outcome measures

Outcome measures
Measure	Cohort 4: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 2: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 Participants Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 Participants Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).	Cohort 5: Placebo n=26 Participants Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=25 Participants Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: Placebo Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) GLP-1, Active: Change at EOT	8.30 Percent change Standard Deviation 13.15	-33.67 Percent change Standard Deviation 16.84	-10.40 Percent change Standard Deviation 10.47	-50.45 Percent change Standard Deviation 12.30	-2.87 Percent change Standard Deviation 20.32	-40.36 Percent change Standard Deviation 26.90	1.63 Percent change Standard Deviation 26.43	-49.73 Percent change Standard Deviation 22.88	—	—	—	—
Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) GLP-1, Inactive: Change at EOT	-20.30 Percent change Standard Deviation NA Standard deviation (SD) data not applicable as only one participant was evaluable for the specified parameter.	0.70 Percent change Standard Deviation NA SD data not applicable as only one participant was evaluable for the specified parameter.	-22.90 Percent change Standard Deviation NA SD data not applicable as only one participant was evaluable for the specified parameter.	-10.93 Percent change Standard Deviation 22.36	1.75 Percent change Standard Deviation 29.20	-8.07 Percent change Standard Deviation 11.30	3.99 Percent change Standard Deviation 29.59	-28.85 Percent change Standard Deviation 16.73	—	—	—	—
Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) Glucagon: Change at EOT	-13.85 Percent change Standard Deviation 18.60	-20.25 Percent change Standard Deviation 25.45	-17.53 Percent change Standard Deviation 19.46	-38.12 Percent change Standard Deviation 16.33	-18.73 Percent change Standard Deviation 21.59	-3.05 Percent change Standard Deviation 36.56	-1.76 Percent change Standard Deviation 21.47	-30.17 Percent change Standard Deviation 25.56	—	—	—	—
Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4) GIP: Change at EOT	18.00 Percent change Standard Deviation 2.83	-46.50 Percent change Standard Deviation 14.85	4.10 Percent change Standard Deviation 24.61	-27.08 Percent change Standard Deviation 25.03	-6.30 Percent change Standard Deviation 7.35	-21.34 Percent change Standard Deviation 39.48	-6.60 Percent change Standard Deviation 19.43	-37.38 Percent change Standard Deviation 23.14	—	—	—	—

Adverse Events

Cohort 1: Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 1: MEDI0382 100 mcg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Cohort 2: Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 2: MEDI0382 150 mcg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort 3: Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Cohort 3: MEDI0382 200 mcg

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Cohort 4: Placebo

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Cohort 4: MEDI0382 200 mcg

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Cohort 5: Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Cohort 5: MEDI0382 300 mcg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Cohort 6: Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 6: MEDI0382 300 mcg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: Placebo n=3 participants at risk Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.	Cohort 1: MEDI0382 100 mcg n=6 participants at risk Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.	Cohort 2: Placebo n=3 participants at risk Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 participants at risk Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 participants at risk Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 participants at risk Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). )	Cohort 4: Placebo n=26 participants at risk Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=25 participants at risk Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 5: Placebo n=5 participants at risk Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=11 participants at risk Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 participants at risk Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 participants at risk Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Eye disorders Diplopia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Infections and infestations Pneumonia mycoplasmal	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])

Other adverse events

Other adverse events
Measure	Cohort 1: Placebo n=3 participants at risk Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.	Cohort 1: MEDI0382 100 mcg n=6 participants at risk Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.	Cohort 2: Placebo n=3 participants at risk Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).	Cohort 2: MEDI0382 150 mcg n=6 participants at risk Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).	Cohort 3: Placebo n=3 participants at risk Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).	Cohort 3: MEDI0382 200 mcg n=7 participants at risk Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). )	Cohort 4: Placebo n=26 participants at risk Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).	Cohort 4: MEDI0382 200 mcg n=25 participants at risk Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).	Cohort 5: Placebo n=5 participants at risk Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).	Cohort 5: MEDI0382 300 mcg n=11 participants at risk Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).	Cohort 6: Placebo n=5 participants at risk Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).	Cohort 6: MEDI0382 300 mcg n=12 participants at risk Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Cardiac disorders Extrasystoles	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Palpitations	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Sinus tachycardia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Supraventricular extrasystoles	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Supraventricular tachycardia	33.3% 1/3 • Number of events 7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Tachycardia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Ventricular extrasystoles	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Ventricular tachycardia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Angina pectoris	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Atrial fibrillation	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Atrioventricular block first degree	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Atrioventricular block second degree	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Eye disorders Abnormal sensation in eye	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Eye disorders Vision blurred	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	28.6% 2/7 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Eye disorders Visual acuity reduced	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Abdominal discomfort	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	12.0% 3/25 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Cardiac disorders Arrhythmia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Ear and labyrinth disorders Vertigo positional	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	50.0% 3/6 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	24.0% 6/25 • Number of events 9 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	18.2% 2/11 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	28.6% 2/7 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Abdominal pain lower	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Constipation	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 2/6 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	11.5% 3/26 • Number of events 5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	24.0% 6/25 • Number of events 7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 8 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	11.5% 3/26 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.0% 4/25 • Number of events 6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 2/12 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Dry mouth	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	42.9% 3/7 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	28.0% 7/25 • Number of events 7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	36.4% 4/11 • Number of events 7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 2/12 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Eructation	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.0% 4/25 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	27.3% 3/11 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Faeces discoloured	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	18.2% 2/11 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Faeces hard	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Faeces soft	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	7.7% 2/26 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.0% 2/25 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Flatulence	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Infrequent bowel movements	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Intra-abdominal haematoma	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Nausea	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	50.0% 3/6 • Number of events 7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	42.9% 3/7 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	19.2% 5/26 • Number of events 7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	52.0% 13/25 • Number of events 39 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	27.3% 3/11 • Number of events 6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	41.7% 5/12 • Number of events 7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Pancreatolithiasis	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Regurgitation	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Salivary hypersecretion	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Gastrointestinal disorders Vomiting	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 2/6 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	42.9% 3/7 • Number of events 8 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	32.0% 8/25 • Number of events 40 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	27.3% 3/11 • Number of events 9 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Asthenia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Early satiety	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	18.2% 2/11 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Fatigue	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 5/25 • Number of events 5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	18.2% 2/11 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Feeling hot	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Injection site discolouration	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Injection site erythema	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	12.0% 3/25 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Injection site haematoma	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Injection site haemorrhage	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	7.7% 2/26 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Injection site pain	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.0% 2/25 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	18.2% 2/11 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Injection site pruritus	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Injection site reaction	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Malaise	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Medical device site erosion	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Medical device site erythema	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	7.7% 2/26 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	12.0% 3/25 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Medical device site injury	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Medical device site irritation	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	11.5% 3/26 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	12.0% 3/25 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Medical device site pain	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Medical device site pruritus	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	7.7% 2/26 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	12.0% 3/25 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Medical device site rash	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Medical device site reaction	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
General disorders Oedema peripheral	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Immune system disorders Allergic oedema	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Infections and infestations Bronchitis	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Infections and infestations Cellulitis	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Infections and infestations Escherichia urinary tract infection	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Infections and infestations Gastrointestinal infection	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Infections and infestations Influenza	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Infections and infestations Nasopharyngitis	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	23.1% 6/26 • Number of events 7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.0% 4/25 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	18.2% 2/11 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	25.0% 3/12 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Infections and infestations Tonsillitis	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Injury, poisoning and procedural complications Burns second degree	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Investigations Alanine aminotransferase increased	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Investigations Blood pressure diastolic increased	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Investigations Blood pressure increased	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	7.7% 2/26 • Number of events 6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Investigations Blood pressure systolic increased	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Investigations Body temperature increased	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Investigations C-reactive protein increased	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Investigations Electrocardiogram st segment depression	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Investigations Heart rate increased	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Investigations Lipase increased	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	18.2% 2/11 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 2/6 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	85.7% 6/7 • Number of events 6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 5/25 • Number of events 5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	36.4% 4/11 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	25.0% 3/12 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Metabolism and nutrition disorders Increased appetite	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Musculoskeletal and connective tissue disorders Ankle deformity	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	28.6% 2/7 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.0% 2/25 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	28.6% 2/7 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Nervous system disorders Dizziness	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	19.2% 5/26 • Number of events 6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.0% 4/25 • Number of events 6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 2/12 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Nervous system disorders Dizziness postural	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Nervous system disorders Dysgeusia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.0% 2/25 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Nervous system disorders Headache	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	33.3% 1/3 • Number of events 6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	57.1% 4/7 • Number of events 6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	7.7% 2/26 • Number of events 6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	36.0% 9/25 • Number of events 10 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	27.3% 3/11 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Nervous system disorders Paraesthesia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Nervous system disorders Presyncope	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Nervous system disorders Sciatica	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Nervous system disorders Somnolence	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Psychiatric disorders Restlessness	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Renal and urinary disorders Chromaturia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Renal and urinary disorders Micturition urgency	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 2/12 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.3% 1/12 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	14.3% 1/7 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Respiratory, thoracic and mediastinal disorders Nasal mucosal ulcer	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	8.0% 2/25 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	20.0% 1/5 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	25.0% 3/12 • Number of events 4 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	4.0% 1/25 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	9.1% 1/11 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 2/12 • Number of events 2 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Skin and subcutaneous tissue disorders Rash	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	12.0% 3/25 • Number of events 3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Skin and subcutaneous tissue disorders Skin reaction	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Vascular disorders Haemorrhage	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Vascular disorders Hypotension	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Vascular disorders Phlebitis	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	3.8% 1/26 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Vascular disorders Thrombophlebitis	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	16.7% 1/6 • Number of events 1 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/6 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/3 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/7 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/26 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/25 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/11 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/5 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])	0.00% 0/12 • From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])

Additional Information

Philip Ambery

MedImmune, LLC

Phone: +44 (0) 1223 895997

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on-going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
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