Trial Outcomes & Findings for A Study to Evaluate the Safety and Tolerability of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus (NCT NCT03745937)

Results Overview

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Baseline (Day -1) through Day 56 (end of Up-titration period)

Results posted on

2020-06-05

Participant Flow

The study was conducted in Germany between 07Jan2019 and 28May2019.

A total of 20 participants were randomized to the study.

Participant milestones

Participant milestones
Measure	Placebo Cohort 1 Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Overall Study STARTED	2	6	3	9
Overall Study COMPLETED	2	5	3	7
Overall Study NOT COMPLETED	0	1	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Cohort 1 Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Overall Study Withdrawal by Subject	0	0	0	1
Overall Study Not-specifed	0	1	0	1

Baseline Characteristics

A Study to Evaluate the Safety and Tolerability of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Total n=20 Participants Total of all reporting groups
Age, Continuous	68.5 Years STANDARD_DEVIATION 3.5 • n=99 Participants	65.3 Years STANDARD_DEVIATION 6.2 • n=107 Participants	62.3 Years STANDARD_DEVIATION 3.5 • n=206 Participants	67.1 Years STANDARD_DEVIATION 5.3 • n=7 Participants	66.0 Years STANDARD_DEVIATION 5.2 • n=31 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	2 Participants n=7 Participants	5 Participants n=31 Participants
Sex: Female, Male Male	2 Participants n=99 Participants	5 Participants n=107 Participants	1 Participants n=206 Participants	7 Participants n=7 Participants	15 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=99 Participants	6 Participants n=107 Participants	3 Participants n=206 Participants	9 Participants n=7 Participants	20 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) White	2 Participants n=99 Participants	6 Participants n=107 Participants	3 Participants n=206 Participants	9 Participants n=7 Participants	20 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1) through Day 56 (end of Up-titration period)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period TEAEs	2 Participants	6 Participants	3 Participants	8 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period TESAEs	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period TEAEs	2 Participants	6 Participants	3 Participants	8 Participants
Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period TESAEs	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1) through Day 56 (end of Up-titration period)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period Supraventricular extrasystoles	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period Ventricular extrasystoles	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period Ventricular tachycardia	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period Atrial fibrillation	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period Atrial fibrillation	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period Supraventricular extrasystoles	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period Ventricular tachycardia	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period Ventricular extrasystoles	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1) through Day 56 (end of Up-titration period)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1) through Day 56 (end of Up-titration period)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examinations findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and, endocrine.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period	0 Participants	3 Participants	0 Participants	4 Participants

PRIMARY outcome

Timeframe: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examination findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and endocrine.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period	0 Participants	3 Participants	0 Participants	4 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1) through Day 56 (end of Up-titration period)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

Population: Pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug and had at least one measurable concentration time point of MEDI0382. Here, only the participants with available data were analyzed for the specified time points.

Area under the plasma concentration time curve over a dosing duration (AUCτ) of MEDI0382 is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=15 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 Day 1	20.9 ng.hr/mL Interval 15.9 to 29.0	—	—	—
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 Day 7	23.7 ng.hr/mL Interval 17.2 to 41.3	—	—	—
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 Day 14	59.9 ng.hr/mL Interval 35.8 to 101.0	—	—	—
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 Day 35	276 ng.hr/mL Interval 183.0 to 694.0	—	—	—
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 Day 42	332 ng.hr/mL Interval 247.0 to 735.0	—	—	—
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 Day 49	434 ng.hr/mL Interval 308.0 to 752.0	—	—	—
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 Day 56	611 ng.hr/mL Interval 343.0 to 2840.0	—	—	—
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 Day 84	661 ng.hr/mL Interval 372.0 to 4740.0	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

Population: The PK population included all participants who received at least 1 dose of study drug and had at least one measurable concentration time point of MEDI0382. Here, only the participants with available data were analyzed for the specified time points.

Maximum observed serum concentration (Cmax) of MEDI0382 is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=15 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 1	1.02 ng/mL Interval 0.447 to 1.84	—	—	—
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 7	1.35 ng/mL Interval 0.934 to 2.51	—	—	—
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 14	3.43 ng/mL Interval 2.02 to 6.37	—	—	—
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 35	15.3 ng/mL Interval 9.74 to 36.1	—	—	—
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 42	17.8 ng/mL Interval 12.7 to 37.8	—	—	—
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 49	24.9 ng/mL Interval 15.2 to 39.0	—	—	—
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 56	32.8 ng/mL Interval 17.7 to 137.0	—	—	—
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 84	35.3 ng/mL Interval 19.7 to 202.0	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

Population: The PK population included all participants who received at least 1 dose of study drug and had at least one measurable concentration time point of MEDI0382. Here, only the participants with available data were analyzed for the specified time points.

Time to observed maximum serum concentration (Tmax) of MEDI0382 is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=15 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 Day 1	6.02 hours Interval 4.0 to 8.0	—	—	—
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 Day 7	6.00 hours Interval 4.0 to 8.0	—	—	—
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 Day 14	6.00 hours Interval 4.0 to 8.0	—	—	—
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 Day 35	6.00 hours Interval 4.0 to 8.0	—	—	—
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 Day 42	6.00 hours Interval 2.0 to 8.0	—	—	—
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 Day 49	6.00 hours Interval 4.0 to 8.0	—	—	—
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 Day 56	6.00 hours Interval 4.0 to 8.0	—	—	—
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 Day 84	6.00 hours Interval 0.0 to 8.0	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

Population: The PK population included all participants who received at least 1 dose of study drug and had at least one measurable concentration time point of MEDI0382. Here, only the participants with available data were analyzed for the specified time points.

Trough concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration (Ctrough) of MEDI0382 is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=15 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Trough Plasma Concentration (Ctrough) of MEDI0382 Day 7	0.551 ng/mL Interval 0.401 to 0.775	—	—	—
Trough Plasma Concentration (Ctrough) of MEDI0382 Day 14	1.46 ng/mL Interval 0.617 to 2.56	—	—	—
Trough Plasma Concentration (Ctrough) of MEDI0382 Day 22	2.01 ng/mL Interval 1.09 to 3.27	—	—	—
Trough Plasma Concentration (Ctrough) of MEDI0382 Day 29	4.65 ng/mL Interval 2.1 to 27.0	—	—	—
Trough Plasma Concentration (Ctrough) of MEDI0382 Day 35	6.92 ng/mL Interval 3.85 to 23.2	—	—	—
Trough Plasma Concentration (Ctrough) of MEDI0382 Day 42	8.85 ng/mL Interval 5.09 to 26.4	—	—	—
Trough Plasma Concentration (Ctrough) of MEDI0382 Day 49	11.0 ng/mL Interval 5.86 to 23.7	—	—	—
Trough Plasma Concentration (Ctrough) of MEDI0382 Day 56	16.3 ng/mL Interval 9.7 to 131.0	—	—	—
Trough Plasma Concentration (Ctrough) of MEDI0382 Day 70	13.6 ng/mL Interval 8.22 to 29.5	—	—	—
Trough Plasma Concentration (Ctrough) of MEDI0382 Day 84	18.8 ng/mL Interval 7.99 to 178.0	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

Population: The PK population included all participants who received at least 1 dose of study drug and had at least one measurable concentration time point of MEDI0382. Here, only the participants with available data were analyzed for the specified time points.

The Ro was calculated using the AUC method which account for the overall exposure measured using the Day 1 and specified time point (Day I). Ro = AUCtrough \[Day I\]/AUCtrough \[Day 1\]; where I is the specified day.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=15 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC Day 1	NA Ratio The data cannot be calculated; as for the specified time, Day I and Day 1 are same, so Ro could not be calculated.	—	—	—
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC Day 7	1.25 Ratio Interval 1.09 to 1.65	—	—	—
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC Day 14	1.40 Ratio Interval 1.22 to 1.72	—	—	—
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC Day 35	1.01 Ratio Interval 0.761 to 1.81	—	—	—
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC Day 42	0.857 Ratio Interval 0.503 to 1.44	—	—	—
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC Day 49	0.904 Ratio Interval 0.603 to 1.18	—	—	—
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC Day 56	1.16 Ratio Interval 0.691 to 5.32	—	—	—
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC Day 84	1.30 Ratio Interval 0.526 to 8.89	—	—	—

SECONDARY outcome

Timeframe: Pre-dose (Day -2), Days 7, 14, 35, 42, 56; Day 21 of 3 week treatment extension, and 28 days post last dose (approximately 5 months)

Population: Immunogenicity population included all participants who received any dose of study drug, and had at least one serum sample for immunogenicity testing.

Number of participants with positive ADA to MEDI0382 are reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment Positive at baseline; not detected post-baseline	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment Positive at baseline	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment Positive post-baseline	0 Participants	3 Participants	0 Participants	4 Participants
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment Positive at baseline and post-baseline	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment Not detected at baseline; positive post-baseline	0 Participants	3 Participants	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline (Day -1) through Day 56 (end of the up-titration period), Day 77 (end of the treatment extension period) and Day 91 (end of the follow-up period)

Population: Intent-to-treat (ITT) population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. During 14 days follow-up (Day 91), last observation carried forward (LOCF) approach was used to calculate the value.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM) Day 77	-10.41 mg/dL Standard Deviation 0.17	-49.24 mg/dL Standard Deviation 25.81	-32.54 mg/dL Standard Deviation 26.78	-39.70 mg/dL Standard Deviation 21.85
Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM) Day 91	-1.80 mg/dL Standard Deviation 25.06	-5.71 mg/dL Standard Deviation 29.28	20.28 mg/dL Standard Deviation 33.40	-13.03 mg/dL Standard Deviation 24.54
Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM) Day 56	-14.96 mg/dL Standard Deviation 16.06	-52.04 mg/dL Standard Deviation 21.73	-22.51 mg/dL Standard Deviation 22.41	-34.25 mg/dL Standard Deviation 14.69

SECONDARY outcome

Timeframe: Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM Days 15-21	13.83 mg/dL Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-44.84 mg/dL Standard Deviation 22.06	-13.72 mg/dL Standard Deviation 18.47	-38.10 mg/dL Standard Deviation 16.50
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM Days 29-35	16.11 mg/dL Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-63.28 mg/dL Standard Deviation 22.23	0.32 mg/dL Standard Deviation 13.60	-40.83 mg/dL Standard Deviation 20.31
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM Days 36-42	22.29 mg/dL Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-47.97 mg/dL Standard Deviation 24.65	-20.03 mg/dL Standard Deviation 7.97	-35.45 mg/dL Standard Deviation 26.96
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM Days 43-49	5.69 mg/dL Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-48.06 mg/dL Standard Deviation 19.98	-19.88 mg/dL Standard Deviation 29.62	-46.84 mg/dL Standard Deviation 20.92
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM Days 50-56	2.02 mg/dL Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-55.21 mg/dL Standard Deviation 22.32	-19.59 mg/dL Standard Deviation 21.63	-37.89 mg/dL Standard Deviation 18.28
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM Days 1-7	37.53 mg/dL Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-34.64 mg/dL Standard Deviation 15.48	-3.96 mg/dL Standard Deviation 3.30	-26.06 mg/dL Standard Deviation 9.47
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM Days 8-14	22.73 mg/dL Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-52.07 mg/dL Standard Deviation 19.14	-14.44 mg/dL Standard Deviation 9.33	-39.86 mg/dL Standard Deviation 10.44
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM Days 22-28	12.54 mg/dL Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-53.38 mg/dL Standard Deviation 29.90	5.88 mg/dL Standard Deviation 7.54	-25.10 mg/dL Standard Deviation 33.72
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM Days 71-77	21.50 mg/dL Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-62.66 mg/dL Standard Deviation 28.88	-19.06 mg/dL Standard Deviation 23.43	-40.20 mg/dL Standard Deviation 31.70

SECONDARY outcome

Timeframe: Baseline (Day -1) through Day 7 (end of Week 1), Day 56 (end of the up-titration period), and Day 77 (end of the treatment extension period)

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Change from baseline in percentage of glucose AUC4Hrs during a standardized breakfast, lunch, and evening meal over time is reported. Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM Day 7 - Breakfast	-3.72 Percent change in Glucose AUC4Hrs Standard Deviation 5.73	-27.90 Percent change in Glucose AUC4Hrs Standard Deviation 2.98	-8.66 Percent change in Glucose AUC4Hrs Standard Deviation 6.75	-25.85 Percent change in Glucose AUC4Hrs Standard Deviation 7.33
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM Day 56 - Breakfast	-21.96 Percent change in Glucose AUC4Hrs Standard Deviation 13.09	-42.22 Percent change in Glucose AUC4Hrs Standard Deviation 10.32	-10.18 Percent change in Glucose AUC4Hrs Standard Deviation 9.18	-32.82 Percent change in Glucose AUC4Hrs Standard Deviation 10.82
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM Day 77 - Breakfast	-10.54 Percent change in Glucose AUC4Hrs Standard Deviation 6.18	-41.52 Percent change in Glucose AUC4Hrs Standard Deviation 9.97	-19.21 Percent change in Glucose AUC4Hrs Standard Deviation 7.20	-32.48 Percent change in Glucose AUC4Hrs Standard Deviation 12.18
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM Day 7 - Evening Meal	-7.81 Percent change in Glucose AUC4Hrs Standard Deviation 17.77	-16.14 Percent change in Glucose AUC4Hrs Standard Deviation 15.55	-10.37 Percent change in Glucose AUC4Hrs Standard Deviation 11.55	-22.58 Percent change in Glucose AUC4Hrs Standard Deviation 8.20
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM Day 7 - Lunch	-3.06 Percent change in Glucose AUC4Hrs Standard Deviation 23.08	-32.55 Percent change in Glucose AUC4Hrs Standard Deviation 10.32	0.32 Percent change in Glucose AUC4Hrs Standard Deviation 9.00	-15.68 Percent change in Glucose AUC4Hrs Standard Deviation 17.75
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM Day 56 - Lunch	-7.35 Percent change in Glucose AUC4Hrs Standard Deviation 11.46	-33.67 Percent change in Glucose AUC4Hrs Standard Deviation 22.60	-24.06 Percent change in Glucose AUC4Hrs Standard Deviation 10.65	-18.30 Percent change in Glucose AUC4Hrs Standard Deviation 13.96
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM Day 77 - Lunch	-7.76 Percent change in Glucose AUC4Hrs Standard Deviation 20.13	-31.10 Percent change in Glucose AUC4Hrs Standard Deviation 32.74	-28.75 Percent change in Glucose AUC4Hrs Standard Deviation 15.12	-21.58 Percent change in Glucose AUC4Hrs Standard Deviation 15.09
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM Day 56 - Evening Meal	-11.07 Percent change in Glucose AUC4Hrs Standard Deviation 1.26	-35.39 Percent change in Glucose AUC4Hrs Standard Deviation 22.14	-22.08 Percent change in Glucose AUC4Hrs Standard Deviation 13.93	-31.44 Percent change in Glucose AUC4Hrs Standard Deviation 10.51
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM Day 77 - Evening Meal	-12.12 Percent change in Glucose AUC4Hrs Standard Deviation 4.61	-26.09 Percent change in Glucose AUC4Hrs Standard Deviation 21.61	-22.06 Percent change in Glucose AUC4Hrs Standard Deviation 14.63	-34.18 Percent change in Glucose AUC4Hrs Standard Deviation 15.11

SECONDARY outcome

Timeframe: Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Change from baseline in coefficient of variation in glucose over 7 days is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM Days 1 - 7	-4.48 Percent of CV Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-0.96 Percent of CV Standard Deviation 4.99	1.51 Percent of CV Standard Deviation 3.84	-2.41 Percent of CV Standard Deviation 3.60
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM Days 29 - 35	-7.92 Percent of CV Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-5.84 Percent of CV Standard Deviation 5.42	-3.24 Percent of CV Standard Deviation 1.68	-2.52 Percent of CV Standard Deviation 5.57
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM Days 8 - 14	-3.67 Percent of CV Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-2.97 Percent of CV Standard Deviation 4.34	2.26 Percent of CV Standard Deviation 3.54	-0.95 Percent of CV Standard Deviation 5.62
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM Days 15 - 21	-8.86 Percent of CV Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-2.65 Percent of CV Standard Deviation 5.40	-1.54 Percent of CV Standard Deviation 1.05	-4.44 Percent of CV Standard Deviation 2.77
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM Days 22 - 28	-4.79 Percent of CV Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-3.70 Percent of CV Standard Deviation 6.86	-2.49 Percent of CV Standard Deviation 2.41	-1.56 Percent of CV Standard Deviation 5.23
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM Days 36 - 42	0.93 Percent of CV Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-4.96 Percent of CV Standard Deviation 6.54	1.39 Percent of CV Standard Deviation 1.69	-1.38 Percent of CV Standard Deviation 4.68
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM Days 43 - 49	-3.96 Percent of CV Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-3.68 Percent of CV Standard Deviation 5.42	2.18 Percent of CV Standard Deviation 5.40	-1.98 Percent of CV Standard Deviation 3.48
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM Days 50 - 56	-2.97 Percent of CV Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-2.94 Percent of CV Standard Deviation 4.61	4.10 Percent of CV Standard Deviation 2.60	-2.36 Percent of CV Standard Deviation 3.23
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM Days 71 - 77	-4.91 Percent of CV Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-2.15 Percent of CV Standard Deviation 4.88	2.60 Percent of CV Standard Deviation 2.21	-0.82 Percent of CV Standard Deviation 3.73

SECONDARY outcome

Timeframe: Baseline (Day -1), Days 7, 14, 21, 28, 35, 42, 49, 56 of the up-titration period, and Day77 (end of the treatment extension period)

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Hyperglycemia (\> 140 mg/dL), normoglycemia (70 -140 mg/dL), and clinically significant hypoglycemia (\< 54 mg/dL).

Outcome measures

SECONDARY outcome

Timeframe: Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Hyperglycemia (\> 140 mg/dL), normoglycemia (70 -140 mg/dL), and clinically significant hypoglycemia (\< 54 mg/dL).

Outcome measures

SECONDARY outcome

Timeframe: Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Change from baseline in estimated HbA1c based on 7-day glucose over time is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time Days 1 - 7	1.31 Percent of HbA1C Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-1.21 Percent of HbA1C Standard Deviation 0.54	-0.14 Percent of HbA1C Standard Deviation 0.12	-0.91 Percent of HbA1C Standard Deviation 0.33
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time Days 8 - 14	0.79 Percent of HbA1C Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-1.81 Percent of HbA1C Standard Deviation 0.67	-0.50 Percent of HbA1C Standard Deviation 0.33	-1.39 Percent of HbA1C Standard Deviation 0.36
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time Days 15 - 21	0.48 Percent of HbA1C Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-1.56 Percent of HbA1C Standard Deviation 0.77	-0.48 Percent of HbA1C Standard Deviation 0.64	-1.33 Percent of HbA1C Standard Deviation 0.58
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time Days 22 - 28	0.44 Percent of HbA1C Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-1.86 Percent of HbA1C Standard Deviation 1.04	0.21 Percent of HbA1C Standard Deviation 0.26	-0.88 Percent of HbA1C Standard Deviation 1.18
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time Days 29 - 35	0.56 Percent of HbA1C Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-2.21 Percent of HbA1C Standard Deviation 0.78	0.01 Percent of HbA1C Standard Deviation 0.47	-1.42 Percent of HbA1C Standard Deviation 0.71
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time Days 36 - 42	0.78 Percent of HbA1C Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-1.67 Percent of HbA1C Standard Deviation 0.86	-0.70 Percent of HbA1C Standard Deviation 0.28	-1.24 Percent of HbA1C Standard Deviation 0.94
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time Days 43 - 49	0.20 Percent of HbA1C Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-1.68 Percent of HbA1C Standard Deviation 0.70	-0.69 Percent of HbA1C Standard Deviation 1.03	-1.63 Percent of HbA1C Standard Deviation 0.73
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time Days 50 - 56	0.07 Percent of HbA1C Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-1.92 Percent of HbA1C Standard Deviation 0.78	-0.68 Percent of HbA1C Standard Deviation 0.75	-1.32 Percent of HbA1C Standard Deviation 0.64
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time Days 71 - 77	0.75 Percent of HbA1C Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-2.18 Percent of HbA1C Standard Deviation 1.01	-0.66 Percent of HbA1C Standard Deviation 0.82	-1.40 Percent of HbA1C Standard Deviation 1.10

SECONDARY outcome

Timeframe: Baseline (Day -1), Days 7, 14, 21, 28, 35, 42, 49, 56 of the up-titration period, and Day77 (end of the treatment extension period)

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Change from baseline in fasting plasma glucose over time is reported. During the Day 21, and Day 28, LOCF approach was used to calculate the value.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Change From Baseline in Fasting Plasma Glucose Over Time Day 7	9.0 mg/dL Standard Deviation 48.1	-32.0 mg/dL Standard Deviation 17.7	13.7 mg/dL Standard Deviation 7.5	-27.1 mg/dL Standard Deviation 12.6
Change From Baseline in Fasting Plasma Glucose Over Time Day 14	-17.5 mg/dL Standard Deviation 31.8	-48.0 mg/dL Standard Deviation 19.2	-3.3 mg/dL Standard Deviation 23.9	-33.9 mg/dL Standard Deviation 19.1
Change From Baseline in Fasting Plasma Glucose Over Time Day 21	-17.5 mg/dL Standard Deviation 31.8	-48.0 mg/dL Standard Deviation 19.2	-3.3 mg/dL Standard Deviation 23.9	-33.9 mg/dL Standard Deviation 19.1
Change From Baseline in Fasting Plasma Glucose Over Time Day 28	-17.5 mg/dL Standard Deviation 31.8	-48.0 mg/dL Standard Deviation 19.2	-3.3 mg/dL Standard Deviation 23.9	-33.9 mg/dL Standard Deviation 19.1
Change From Baseline in Fasting Plasma Glucose Over Time Day 35	28.5 mg/dL Standard Deviation 16.3	-46.8 mg/dL Standard Deviation 25.8	5.7 mg/dL Standard Deviation 29.2	-44.4 mg/dL Standard Deviation 15.8
Change From Baseline in Fasting Plasma Glucose Over Time Day 49	23.5 mg/dL Standard Deviation 20.5	-45.6 mg/dL Standard Deviation 23.0	-0.3 mg/dL Standard Deviation 35.6	-38.1 mg/dL Standard Deviation 23.7
Change From Baseline in Fasting Plasma Glucose Over Time Day 42	9.0 mg/dL Standard Deviation 14.1	-42.6 mg/dL Standard Deviation 24.5	2.0 mg/dL Standard Deviation 27.9	-35.1 mg/dL Standard Deviation 24.6
Change From Baseline in Fasting Plasma Glucose Over Time Day 56	-7.5 mg/dL Standard Deviation 37.5	-52.8 mg/dL Standard Deviation 24.4	-9.7 mg/dL Standard Deviation 26.4	-31.3 mg/dL Standard Deviation 24.6
Change From Baseline in Fasting Plasma Glucose Over Time Day 77	1.0 mg/dL Standard Deviation 21.2	-47.6 mg/dL Standard Deviation 34.2	-9.7 mg/dL Standard Deviation 32.9	-28.6 mg/dL Standard Deviation 20.5

SECONDARY outcome

Timeframe: Baseline (Day -1) through Day 77 (end of the treatment extension period)

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group.

Change from baseline in HbA1c is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Change From Baseline in HbA1c	0.10 Percent of HbA1C Standard Deviation 0.00	-1.44 Percent of HbA1C Standard Deviation 0.52	-0.40 Percent of HbA1C Standard Deviation 0.35	-0.59 Percent of HbA1C Standard Deviation 0.74

SECONDARY outcome

Timeframe: Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP)

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Absolute change from baseline in body weight is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Absolute Change From Baseline in Body Weight Day 56	-0.30 Kg Standard Deviation 0.00	-5.27 Kg Standard Deviation 3.92	-1.70 Kg Standard Deviation 1.80	-2.89 Kg Standard Deviation 4.15
Absolute Change From Baseline in Body Weight Day 77	-1.25 Kg Standard Deviation 0.64	-6.96 Kg Standard Deviation 4.66	-1.50 Kg Standard Deviation 1.56	-4.56 Kg Standard Deviation 4.41

SECONDARY outcome

Timeframe: Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP)

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Percentage change from baseline in body weight is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Percentage Change From Baseline in Body Weight Day 56	-0.33 Percentage change in body weight Standard Deviation 0.01	-5.06 Percentage change in body weight Standard Deviation 3.16	-1.96 Percentage change in body weight Standard Deviation 2.09	-3.20 Percentage change in body weight Standard Deviation 4.78
Percentage Change From Baseline in Body Weight Day 77	-1.38 Percentage change in body weight Standard Deviation 0.74	-6.88 Percentage change in body weight Standard Deviation 3.81	-1.76 Percentage change in body weight Standard Deviation 1.79	-5.08 Percentage change in body weight Standard Deviation 5.00

SECONDARY outcome

Timeframe: Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Absolute change from baseline in body weight to the end of each week of the up-titration period is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 7	-2.05 Kg Standard Deviation 1.06	-1.78 Kg Standard Deviation 0.86	-0.70 Kg Standard Deviation 1.64	0.49 Kg Standard Deviation 4.87
Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 14	-1.95 Kg Standard Deviation 0.35	-2.72 Kg Standard Deviation 0.68	-0.73 Kg Standard Deviation 1.10	0.08 Kg Standard Deviation 4.19
Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 35	-0.60 Kg Standard Deviation 0.99	-3.86 Kg Standard Deviation 3.24	-0.27 Kg Standard Deviation 1.25	-1.70 Kg Standard Deviation 4.37
Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 42	-0.10 Kg Standard Deviation 0.14	-4.40 Kg Standard Deviation 3.22	-1.57 Kg Standard Deviation 1.50	-2.00 Kg Standard Deviation 4.56
Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 49	0.10 Kg Standard Deviation 0.14	-4.94 Kg Standard Deviation 3.63	-1.57 Kg Standard Deviation 1.19	-3.30 Kg Standard Deviation 5.08
Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 56	-0.30 Kg Standard Deviation 0.00	-5.27 Kg Standard Deviation 3.92	-1.70 Kg Standard Deviation 1.80	-2.89 Kg Standard Deviation 4.15

SECONDARY outcome

Timeframe: Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Percentage change from baseline in body weight to the end of each week of the up-titration period is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 35	-0.64 Percentage change in body weight Standard Deviation 1.06	-3.89 Percentage change in body weight Standard Deviation 2.99	-0.27 Percentage change in body weight Standard Deviation 1.50	-1.78 Percentage change in body weight Standard Deviation 4.95
Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 42	-0.11 Percentage change in body weight Standard Deviation 0.15	-4.43 Percentage change in body weight Standard Deviation 2.93	-1.81 Percentage change in body weight Standard Deviation 1.74	-2.09 Percentage change in body weight Standard Deviation 5.16
Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 49	0.11 Percentage change in body weight Standard Deviation 0.16	-4.95 Percentage change in body weight Standard Deviation 3.32	-1.82 Percentage change in body weight Standard Deviation 1.37	-3.52 Percentage change in body weight Standard Deviation 5.67
Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 56	-0.33 Percentage change in body weight Standard Deviation 0.01	-5.06 Percentage change in body weight Standard Deviation 3.16	-1.96 Percentage change in body weight Standard Deviation 2.09	-3.20 Percentage change in body weight Standard Deviation 4.78
Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 7	-2.22 Percentage change in body weight Standard Deviation 1.09	-1.83 Percentage change in body weight Standard Deviation 0.95	-0.77 Percentage change in body weight Standard Deviation 1.96	0.67 Percentage change in body weight Standard Deviation 5.69
Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period Day 14	-2.13 Percentage change in body weight Standard Deviation 0.32	-2.76 Percentage change in body weight Standard Deviation 0.62	-0.83 Percentage change in body weight Standard Deviation 1.30	0.22 Percentage change in body weight Standard Deviation 4.85

SECONDARY outcome

Timeframe: Baseline (Day -1) through Day 77 (end of the treatment extension period)

Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points.

Percentage of participants achieving greater than 5% body weight loss from baseline is reported.

Outcome measures

Outcome measures
Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period Day 14	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period Day 35	0 Percentage of participants	40 Percentage of participants	0 Percentage of participants	25 Percentage of participants
Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period Day 42	0 Percentage of participants	40 Percentage of participants	0 Percentage of participants	25 Percentage of participants
Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period Day 7	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period Day 49	0 Percentage of participants	60 Percentage of participants	0 Percentage of participants	50 Percentage of participants
Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period Day 56	0 Percentage of participants	50 Percentage of participants	0 Percentage of participants	28.6 Percentage of participants
Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period Day 77	0 Percentage of participants	80 Percentage of participants	0 Percentage of participants	71.4 Percentage of participants

Adverse Events

Placebo Cohort 1

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

MEDI0382 Cohort 1

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo Cohort 2

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

MEDI0382 Cohort 2

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Lars Hansen

MedImmune, LLC

Phone: +1 301 398 4563

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 ongoing 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 21 - Hyperglycemia	-3.65 Percentage of time spent Standard Deviation 8.10	-38.50 Percentage of time spent Standard Deviation 13.38	10.42 Percentage of time spent Standard Deviation 16.04	-22.92 Percentage of time spent Standard Deviation 30.64
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 42 - Hyperglycemia	-19.80 Percentage of time spent Standard Deviation 7.37	-38.33 Percentage of time spent Standard Deviation 28.49	-20.49 Percentage of time spent Standard Deviation 32.81	-36.85 Percentage of time spent Standard Deviation 27.44
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 49 - Hyperglycemia	9.90 Percentage of time spent Standard Deviation 19.89	-49.79 Percentage of time spent Standard Deviation 5.58	-16.32 Percentage of time spent Standard Deviation 41.07	-42.71 Percentage of time spent Standard Deviation 27.02
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 77 - Hyperglycemia	-21.35 Percentage of time spent Standard Deviation 14.00	-46.04 Percentage of time spent Standard Deviation 20.90	-26.74 Percentage of time spent Standard Deviation 30.09	-35.27 Percentage of time spent Standard Deviation 32.58
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 7 - Normoglycemia	19.27 Percentage of time spent Standard Deviation 31.67	39.58 Percentage of time spent Standard Deviation 13.79	7.64 Percentage of time spent Standard Deviation 15.36	22.66 Percentage of time spent Standard Deviation 18.04
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 14 - Normoglycemia	5.21 Percentage of time spent Standard Deviation 11.79	41.25 Percentage of time spent Standard Deviation 10.25	13.89 Percentage of time spent Standard Deviation 29.47	25.78 Percentage of time spent Standard Deviation 24.35
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 42 - Normoglycemia	19.79 Percentage of time spent Standard Deviation 7.37	34.58 Percentage of time spent Standard Deviation 26.78	16.67 Percentage of time spent Standard Deviation 37.80	36.72 Percentage of time spent Standard Deviation 27.45
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 49 - Normoglycemia	-10.42 Percentage of time spent Standard Deviation 20.62	47.92 Percentage of time spent Standard Deviation 5.46	4.86 Percentage of time spent Standard Deviation 37.81	41.82 Percentage of time spent Standard Deviation 28.31
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 56 - Normoglycemia	19.79 Percentage of time spent Standard Deviation 4.42	40.42 Percentage of time spent Standard Deviation 24.78	17.31 Percentage of time spent Standard Deviation 27.47	30.51 Percentage of time spent Standard Deviation 29.37
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 77 - Normoglycemia	18.75 Percentage of time spent Standard Deviation 14.73	43.13 Percentage of time spent Standard Deviation 19.72	21.88 Percentage of time spent Standard Deviation 29.04	27.73 Percentage of time spent Standard Deviation 36.31
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 7 - Hypoglycemia	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 14 - Hypoglycemia	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 21 - Hypoglycemia	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 42 - Hypoglycemia	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 77 - Hypoglycemia	0.00 Percentage of time spent Standard Deviation 0.00	0.83 Percentage of time spent Standard Deviation 1.86	0.00 Percentage of time spent Standard Deviation 0.00	1.73 Percentage of time spent Standard Deviation 3.73
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 7 - Hyperglycemia	-19.79 Percentage of time spent Standard Deviation 32.41	-39.06 Percentage of time spent Standard Deviation 15.18	-7.29 Percentage of time spent Standard Deviation 14.77	-22.66 Percentage of time spent Standard Deviation 18.06
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 14 - Hyperglycemia	-5.73 Percentage of time spent Standard Deviation 12.52	-41.67 Percentage of time spent Standard Deviation 12.17	-15.63 Percentage of time spent Standard Deviation 27.14	-25.91 Percentage of time spent Standard Deviation 24.31
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 28 - Hyperglycemia	-9.90 Percentage of time spent Standard Deviation 18.41	-33.54 Percentage of time spent Standard Deviation 28.12	13.19 Percentage of time spent Standard Deviation 33.09	-21.88 Percentage of time spent Standard Deviation 25.20
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 35 - Hyperglycemia	-6.01 Percentage of time spent Standard Deviation 6.84	-51.24 Percentage of time spent Standard Deviation 8.80	2.49 Percentage of time spent Standard Deviation 25.74	-32.30 Percentage of time spent Standard Deviation 27.21
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 56 - Hyperglycemia	-20.31 Percentage of time spent Standard Deviation 3.68	-50.21 Percentage of time spent Standard Deviation 18.51	-16.96 Percentage of time spent Standard Deviation 26.89	-31.40 Percentage of time spent Standard Deviation 28.11
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 21 - Normoglycemia	3.13 Percentage of time spent Standard Deviation 8.84	39.06 Percentage of time spent Standard Deviation 14.23	-11.11 Percentage of time spent Standard Deviation 16.84	19.53 Percentage of time spent Standard Deviation 30.77
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 28 - Normoglycemia	9.90 Percentage of time spent Standard Deviation 18.41	20.21 Percentage of time spent Standard Deviation 18.69	-13.54 Percentage of time spent Standard Deviation 34.34	21.13 Percentage of time spent Standard Deviation 25.07
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 35 - Normoglycemia	5.48 Percentage of time spent Standard Deviation 7.60	39.35 Percentage of time spent Standard Deviation 10.46	-2.14 Percentage of time spent Standard Deviation 26.29	27.81 Percentage of time spent Standard Deviation 27.30
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 28 - Hypoglycemia	0.00 Percentage of time spent Standard Deviation 0.00	1.04 Percentage of time spent Standard Deviation 2.33	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 35 - Hypoglycemia	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 49 - Hypoglycemia	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM Day 56 - Hypoglycemia	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00

Measure	Placebo Cohort 1 n=2 Participants Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 Participants Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 Participants Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 8 - 14 (Hyperglycemia)	17.22 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-46.85 Percentage of time spent Standard Deviation 16.11	-17.00 Percentage of time spent Standard Deviation 10.30	-35.82 Percentage of time spent Standard Deviation 20.15
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 15 - 21 (Hyperglycemia)	19.80 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-40.52 Percentage of time spent Standard Deviation 19.30	-9.16 Percentage of time spent Standard Deviation 14.98	-33.74 Percentage of time spent Standard Deviation 26.94
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 36 - 42 (Hyperglycemia)	11.77 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-42.48 Percentage of time spent Standard Deviation 25.55	-17.21 Percentage of time spent Standard Deviation 7.69	-37.81 Percentage of time spent Standard Deviation 30.52
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 43 - 49 (Hyperglycemia)	9.08 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-41.92 Percentage of time spent Standard Deviation 19.10	-16.46 Percentage of time spent Standard Deviation 21.74	-44.62 Percentage of time spent Standard Deviation 30.95
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 15 - 21 (Normoglycemia)	-19.20 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	40.36 Percentage of time spent Standard Deviation 19.14	9.30 Percentage of time spent Standard Deviation 15.08	31.82 Percentage of time spent Standard Deviation 27.12
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 22 - 28 (Normoglycemia)	-12.10 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	32.09 Percentage of time spent Standard Deviation 24.74	-6.27 Percentage of time spent Standard Deviation 12.58	22.44 Percentage of time spent Standard Deviation 26.08
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 29 - 35 (Normoglycemia)	-19.49 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	42.95 Percentage of time spent Standard Deviation 16.13	-3.71 Percentage of time spent Standard Deviation 15.81	36.13 Percentage of time spent Standard Deviation 30.86
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 36 - 42 (Normoglycemia)	-11.31 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	40.62 Percentage of time spent Standard Deviation 24.51	17.15 Percentage of time spent Standard Deviation 8.75	37.45 Percentage of time spent Standard Deviation 29.72
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 71 - 77 (Normoglycemia)	-18.27 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	46.39 Percentage of time spent Standard Deviation 29.99	15.08 Percentage of time spent Standard Deviation 17.47	37.93 Percentage of time spent Standard Deviation 38.28
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 1 - 7 (Hypoglycemia)	0.00 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 8 - 14 (Hypoglycemia)	0.00 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	1.20 Percentage of time spent Standard Deviation 1.68	0.00 Percentage of time spent Standard Deviation 0.00	0.28 Percentage of time spent Standard Deviation 0.68
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 36 - 42 (Hypoglycemia)	0.00 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 71 - 77 (Hypoglycemia)	0.00 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	2.16 Percentage of time spent Standard Deviation 3.23	0.15 Percentage of time spent Standard Deviation 0.26	0.44 Percentage of time spent Standard Deviation 0.59
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 1 - 7 (Normoglycemia)	-19.94 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	32.58 Percentage of time spent Standard Deviation 11.48	9.10 Percentage of time spent Standard Deviation 5.99	23.34 Percentage of time spent Standard Deviation 15.55
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 8 - 14 Normoglycemia)	-16.47 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	43.41 Percentage of time spent Standard Deviation 11.65	17.07 Percentage of time spent Standard Deviation 10.85	33.32 Percentage of time spent Standard Deviation 20.61
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 1 - 7 (Hyperglycemia)	20.70 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-32.73 Percentage of time spent Standard Deviation 12.03	-8.87 Percentage of time spent Standard Deviation 5.08	-23.38 Percentage of time spent Standard Deviation 15.92
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 22 - 28 (Hyperglycemia)	12.25 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-40.92 Percentage of time spent Standard Deviation 29.12	6.55 Percentage of time spent Standard Deviation 12.31	-26.31 Percentage of time spent Standard Deviation 25.76
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 29 - 35 (Hyperglycemia)	20.10 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-51.69 Percentage of time spent Standard Deviation 17.49	4.03 Percentage of time spent Standard Deviation 15.26	-38.19 Percentage of time spent Standard Deviation 31.32
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 50 - 56 (Hyperglycemia)	6.82 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-47.70 Percentage of time spent Standard Deviation 21.30	-18.70 Percentage of time spent Standard Deviation 16.86	-34.90 Percentage of time spent Standard Deviation 27.76
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 71 - 77 (Hyperglycemia)	18.57 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	-53.98 Percentage of time spent Standard Deviation 27.16	-16.06 Percentage of time spent Standard Deviation 17.53	-40.21 Percentage of time spent Standard Deviation 37.99
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 43 - 49 (Normoglycemia)	-8.63 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	40.85 Percentage of time spent Standard Deviation 17.93	14.07 Percentage of time spent Standard Deviation 19.02	42.81 Percentage of time spent Standard Deviation 30.11
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 50 - 56 (Normoglycemia)	-6.37 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	44.10 Percentage of time spent Standard Deviation 19.74	18.10 Percentage of time spent Standard Deviation 14.94	33.61 Percentage of time spent Standard Deviation 27.62
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 15 - 21 (Hypoglycemia)	0.00 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00	0.20 Percentage of time spent Standard Deviation 0.49
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 22 - 28 Hypoglycemia)	0.00 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	1.09 Percentage of time spent Standard Deviation 2.28	0.00 Percentage of time spent Standard Deviation 0.00	0.79 Percentage of time spent Standard Deviation 1.76
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 29 - 35 (Hypoglycemia)	0.00 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	0.27 Percentage of time spent Standard Deviation 0.61	0.00 Percentage of time spent Standard Deviation 0.00	0.00 Percentage of time spent Standard Deviation 0.00
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 43 - 49 (Hypoglycemia)	0.00 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	0.09 Percentage of time spent Standard Deviation 0.20	0.40 Percentage of time spent Standard Deviation 0.70	0.15 Percentage of time spent Standard Deviation 0.37
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM Days 50 - 56 (Hypoglycemia)	0.00 Percentage of time spent Standard Deviation NA Standard deviation is not reported as only one participant was evaluable for the specified arm.	0.06 Percentage of time spent Standard Deviation 0.14	0.20 Percentage of time spent Standard Deviation 0.35	0.15 Percentage of time spent Standard Deviation 0.37

Measure	Placebo Cohort 1 n=2 participants at risk Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP).	MEDI0382 Cohort 1 n=6 participants at risk Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.	Placebo Cohort 2 n=3 participants at risk Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.	MEDI0382 Cohort 2 n=9 participants at risk Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Cardiac disorders Atrial fibrillation	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Cardiac disorders Supraventricular extrasystoles	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Cardiac disorders Ventricular extrasystoles	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Cardiac disorders Ventricular tachycardia	50.0% 1/2 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Ear and labyrinth disorders Vertigo	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	16.7% 1/6 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Abdominal distension	50.0% 1/2 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	16.7% 1/6 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 1/3 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	22.2% 2/9 • Number of events 3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Abdominal pain	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	22.2% 2/9 • Number of events 4 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 1/3 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Constipation	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	66.7% 4/6 • Number of events 4 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 1/3 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	22.2% 2/9 • Number of events 3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 2/6 • Number of events 2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 3/9 • Number of events 8 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Dyspepsia	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 1/3 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	44.4% 4/9 • Number of events 4 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Eructation	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Intra-abdominal haematoma	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 1/3 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Nausea	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 2/6 • Number of events 3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 4 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Gastrointestinal disorders Vomiting	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
General disorders Early satiety	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	44.4% 4/9 • Number of events 4 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
General disorders Fatigue	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	22.2% 2/9 • Number of events 2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
General disorders Injection site erythema	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 2/6 • Number of events 3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
General disorders Injection site reaction	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 2/6 • Number of events 4 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	44.4% 4/9 • Number of events 15 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Infections and infestations Herpes zoster	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	16.7% 1/6 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Infections and infestations Nasopharyngitis	50.0% 1/2 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	33.3% 2/6 • Number of events 2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	66.7% 2/3 • Number of events 4 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Investigations Blood pressure diastolic increased	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	16.7% 1/6 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Metabolism and nutrition disorders Appetite disorder	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	66.7% 4/6 • Number of events 4 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	16.7% 1/6 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	16.7% 1/6 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	16.7% 1/6 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Nervous system disorders Dizziness	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	16.7% 1/6 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Nervous system disorders Lethargy	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Nervous system disorders Presyncope	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	16.7% 1/6 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	16.7% 1/6 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/9 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/2 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/6 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	0.00% 0/3 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)	11.1% 1/9 • Number of events 1 • Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)