Study of MEDI0382 in Combination With Dapagliflozin and M... | NCT03444584

ID	Type	Description	Link
2017-002817-78	EudraCT Number

Label	Type	Description	Intervention Names
MEDI0382	Experimental	Participants will receive subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	Drug: MEDI0382 Drug: Dapaglifozin Drug: Metformin
Placebo	Placebo Comparator	Participants will receive subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period	Drug: Placebo Drug: Dapaglifozin Drug: Metformin

Name	Type	Description	Arm Group Labels	Other Names
MEDI0382	Drug	Subcutaneous dose of MEDI0382 (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days).	MEDI0382

Measure	Description	Time Frame
Change From Baseline to Day 28 in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4hrs) as Measured by Mixed-meal Tolerance Test (MMTT)	The MMTT test involved the consumption of a standardised liquid meal (nutritional supplement of fat, carbohydrate, and protein) within 5 minutes. On Day -1 and on Day 28, following a minimum 10 hour fast, serial of blood samples were obtained prior and through 240 minutes after consumption of standardized meal for the measurement of glucose metabolism (with no additional food intake during this time).	Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -1 (Baseline) and Day 28
Percent Change From Baseline to Day 28 in Plasma Glucose AUC0-4hrs as Measured by MMTT	The MMTT test involved the consumption of a standardised liquid meal (nutritional supplement of fat, carbohydrate, and protein)within 5 minutes. On Day -1 and on Day 28, following a minimum 10-hour fast, serial of blood samples were obtained prior and through 240 minutes after consumption of standardized meal for the measurement of glucose metabolism (with no additional food intake during this time).	Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -1 (Baseline) and Day 28

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female participants aged >= 18 years at screening.
Provision of signed and dated informed consent form (ICF) prior to any study specific procedures.
Body mass index between 25 kg/m^2 and 40 kg/m^2 (inclusive) at screening.
Hemoglobin A1c range between 7.0% and 10.0% (inclusive) at the time of screening.
Diagnosed with T2DM and treated with of metformin monotherapy (MTD > 1 g) at least 8 weeks prior to screening or treated with stable, oral doses of dapagliflozin 10 mg and metformin (MTD > 1 g) for at least 3 months prior screening.
Participants prescribed oral dual therapy with sulphonylurea, glitinide, or dipeptidyl peptidase-4 inhibitor (in addition to metformin) may be eligible to enter the study following a washout period of these medications totaling at least 28 days before initial screening evaluations have been completed.
Participants treated with stable doses of metformin (MTD > 1 g) with canagliflozin (maximum dose of 300 mg/day), or metformin (MTD > 1 g) with empaglifozin (maximum dose of 25mg/day) for at least 3 months prior to screening may be eligible to enter the study after switching to dapagliflozin.
Female participants of childbearing potential must have a negative pregnancy test at screening and randomization and must not be lactating.
Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from screening and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female participant to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

Exclusion Criteria:

History of, or any existing condition that in the opinion of the investigator would interfere with evaluation of the investigational product, put the participant at risk, influence the participant's ability to participate, or affect the interpretation of the results of the study and/or any participant unable or unwilling to follow study procedures.
Any participant who has received another investigational product not included in the protocol as part of a clinical trial or a glucagon-like peptide-1 (GLP-1) analogue or sodium-glucose cotransporter-2 (SGLT2)-containing preparation (excluding dapagliflozin, canagliflozin, empagliflozin) within the last 30 days or 5 half-lives of the drug (whichever is longest) at the time of screening.
Any participant who has received any of the following medications prior to the start of the screening period (Visit 1) or prior to the study start period (Visit 4):
- Concurrent use of any medicinal products, or herbal or over-the-counter (OTC) preparations licensed for control of body weight or appetite at the time of screening (Visit 1)
- Concurrent or previous use of drugs approved for weight loss (eg, orlistat, bupropion-naltrexone, phentermine-topiramate, phentermine, lorcaserin) within the last 30 days or 5 half-lives of the drug (whichever is longest) at the time of screening (Visit 1)
- Concurrent use of aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily and within the last 72 hours prior to the start of the study (Visit 4)
- Concurrent use of paracetamol (acetaminophen) or paracetamol-containing preparations at a total daily dose of greater than 3000 mg and within the last 72 hours prior to the start of the study (Visit 4)
- Concurrent use of ascorbic acid (vitamin C) supplements at a total daily dose greater than 1000 mg and within the last 72 hours prior to the start of the study (Visit 4)
- Concurrent use of opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying and within the last 72 hours prior to the start of the study (Visit 4)
Concurrent participation in another study of any kind and repeat randomization in this study is prohibited.
Severe allergy/hypersensitivity to any of the proposed study treatments or excipients.
Diagnosis of type 1 diabetes mellitus, maturity-onset diabetes of the young, or latent autoimmune diabetes of adulthood or presence of anti-glutamic acid decarboxylase, anti-islet cell, or anti-insulin antibodies.
Symptoms of acutely decompensate blood glucose control (eg, thirst, polyuria, weight loss) at screening or randomization, a history of diabetes ketoacidosis (DKA), or hyperosmolar nonketotic coma or treatment with daily subcutaneous insulin within 90 days prior to screening.
Fasting hyperglycemia (> 250 mg/dL/ > 13.9 mmol/L) prior to randomization.
C-peptide level < lower limit of normal (LLN).
History of acute or chronic pancreatitis or pancreatectomy.
Hypertriglyceridemia (> 400 mg/dL) at screening.
Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper gastrointestinal (GI) tract (including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data.
Significant hepatic disease (except for nonalcoholic steatohepatitis or nonalcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results at screening:
- Aspartate transaminase (AST) >= 3 × upper limit of normal (ULN)
- Alanine transaminase (ALT) >= 3 × ULN
- Total bilirubin (TBL) >= 2 × ULN
Impaired renal function defined as estimated glomerular filtration rate (eGFR) <= 60 mL/minute/1.73m^2 at screening (eGFR according to Modification of Diet in Renal Disease [MDRD] using the isotope dilution mass spectrometry-traceable MDRD Study Equation (SI units).
Use of loop diuretics within 1 month prior to screening.
Poorly controlled hypertension as defined below:
- Systolic blood pressure (BP) > 160 mm Hg
- Diastolic BP or >= 100 mm Hg After 10 minutes of supine rest and confirmed by repeated measurement at screening (Visit 1 for all participants).
Unstable angina pectoris, myocardial infarction, transient ischemic attack, or stroke within 3 months prior to screening, or participants who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening.
Severe congestive heart failure (New York Heart Association Class III and IV)
Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia.
Hemoglobinopathy, hemolytic anemia, or chronic anemia (hemoglobin concentration < 11.5 g/dL [115 g/L] for males and < 10.5 g/dL [105 g/L] for females) at screening or any other condition known to interfere with interpretation of HbA1c measurement.
History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer.
Any positive results for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus antibody.
Recent viral infection or illness requiring the use of antibiotics in the month prior to screening (Visit 1) for participants on dual therapy or prior to run-in period (Visit 2) for participants on monotherapy.
History of recurrent (at least 2) urinary tract and/or genital tract infections (including mycotic infections such as thrush) within 6 months prior to screening.
Substance dependence likely to impact participant safety or compliance with study procedures.
Involvement of any AstraZeneca, MedImmune, contract research organization, or study site employees and their close relatives.

Name	Affiliation	Role
Stephen Bain, MD	Joint Clinical Research Facility	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Magdeburg		39120	Germany
Research Site

Label	URL
D5670C00007-Clinical-Protocol draft Redacted	View source
D5670C00007 Statistical Analysis Plan Redacted	View source

ID	Title	Description
FG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
FG001	MEDI0382

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 19, 2017	Dec 5, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to Day 28 in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4hrs) as Measured by Mixed-meal Tolerance Test (MMTT)

The MMTT test involved the consumption of a standardised liquid meal (nutritional supplement of fat, carbohydrate, and protein) within 5 minutes. On Day -1 and on Day 28, following a minimum 10 hour fast, serial of blood samples were obtained prior and through 240 minutes after consumption of standardized meal for the measurement of glucose metabolism (with no additional food intake during this time).

Intent-to-treat (ITT) population included all participants who received any dose of study drugs analyzed according to their randomized treatment group. Here, number of participants analyzed "N" signifies participants who were analyzed for the specified outcome measure.

Posted

Least Squares Mean

95% Confidence Interval

hr·mg/dL

Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -1 (Baseline) and Day 28

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants	OG00022 OG00124

Title

Denominators

Categories

Title	Measurements
	OG000-11.28(-51.05 to 28.50) OG001-154.37(-192.45 to -116.29)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		<0.0001		LS mean difference	-143.09			2-Sided	95	-198.20	-87.98					Superiority

Primary

Percent Change From Baseline to Day 28 in Plasma Glucose AUC0-4hrs as Measured by MMTT

The MMTT test involved the consumption of a standardised liquid meal (nutritional supplement of fat, carbohydrate, and protein)within 5 minutes. On Day -1 and on Day 28, following a minimum 10-hour fast, serial of blood samples were obtained prior and through 240 minutes after consumption of standardized meal for the measurement of glucose metabolism (with no additional food intake during this time).

An ITT population included all participants who received any dose of study drugs and analyzed according to their randomized treatment group. Here, number of participants analyzed "N" signifies participants who were analyzed for the specified outcome measure.

Posted

Least Squares Mean

95% Confidence Interval

Percent change in Glucose AUC0-4hrs

Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -1 (Baseline) and Day 28

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Secondary

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

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.

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

Posted

Count of Participants

Participants

Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Secondary

Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Reported as TEAEs

Number of participants with abnormal 12-lead ECG reported as TEAEs are reported.

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

Posted

Count of Participants

Participants

Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Vital Signs Reported as TEAEs

Number of participants with abnormal vital signs reported as TEAEs are reported.

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

Posted

Count of Participants

Participants

Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Physical Examinations Reported as TEAEs

Number of participants with abnormal physical examinations reported as TEAEs are reported.

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

Posted

Count of Participants

Participants

Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.

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

Posted

Count of Participants

Participants

Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants

Secondary

Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of MEDI0382

Area under the plasma concentration time curve from time zero to infinity (AUC [0-∞]) of MEDI0382 is reported.

MEDI0382 pharmacokinetic (PK) population included all participants who received at least 1 dose of MEDI0382 and had at least 1 MEDI0382 PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Posted

Geometric Mean

Full Range

ng.hr/mL

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

ID	Title	Description
OG000	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of Dapagliflozin

Area under the plasma concentration time curve from time zero to infinity (AUC [0-∞]) of Dapagliflozin is reported.

Dapagliflozin PK population included all participants who received at least 1 dose of dapagliflozin and had at least 1 dapagliflozin PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Posted

Geometric Mean

Full Range

ng.hr/mL

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts

Secondary

Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of MEDI0382

Area under the plasma concentration-time curve during the dosing period (AUCtau) of MEDI0382 is reported.

MEDI0382 PK population included all participants who received at least 1 dose of MEDI0382 and had at least 1 MEDI0382 PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Posted

Geometric Mean

Full Range

ng.hr/mL

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

ID	Title	Description
OG000	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants	OG000

Secondary

Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of Dapagliflozin

Area under the plasma Concentration-time curve during the dosing period (AUCtau) of Dapagliflozin is reported.

Posted

Geometric Mean

Full Range

ng.hr/mL

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts

Secondary

Maximum Observed Serum Concentration (Cmax) of MEDI0382

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

Posted

Geometric Mean

Full Range

ng/mL

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

ID	Title	Description
OG000	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants	OG000

Secondary

Maximum Observed Serum Concentration (Cmax) of Dapagliflozin

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

Posted

Geometric Mean

Full Range

ng/mL

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants

Secondary

Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI0382

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

Posted

Median

Full Range

Hours

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

ID	Title	Description
OG000	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants	OG000

Secondary

Time to Reach Maximum Observed Serum Concentration (Tmax) of Dapagliflozin

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

Posted

Median

Full Range

Hours

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants

Secondary

Terminal Elimination Half-life (t½) of MEDI0382

Terminal half-life is the time required for the plasma concentration to fall by 50% during the terminal phase. The t½ of MEDI0382 is reported.

Posted

Geometric Mean

Full Range

Hours

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

ID	Title	Description
OG000	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants	OG000

Secondary

Terminal Elimination Half-life (t½) of Dapagliflozin

Terminal half-life is the time required for the plasma concentration to fall by 50% during the terminal phase. The t½ of Dapagliflozin is reported.

Posted

Geometric Mean

Full Range

Hours

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts

Secondary

Apparent Clearance (CL/F) of MEDI0382

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The CL/F of MEDI0382 is reported.

Posted

Geometric Mean

Full Range

L/hr

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

ID	Title	Description
OG000	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts
Participants	OG000

Secondary

Apparent Clearance (CL/F) of Dapagliflozin

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The CL/F of Dapagliflozin is reported.

Posted

Geometric Mean

Full Range

L/Hr

Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts

Secondary

Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI0382

Number of participants with positive Anti-drug antibodies (ADA) titer to MEDI0382 are reported.

Immunogenicity population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to the treatment they actually received and had at least one serum sample for immunogenicity testing. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Posted

Count of Participants

Participants

Day 1 (pre-dose), on Day 29 , and 28 days post last dose (end of study visit; approximately 8 weeks)

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Units	Counts

Secondary

Change From Baseline in Plasma Glucose AUC24-hrs to the End of Each Dosing Level as Measured by Continuous Glucose Monitoring (CGM)

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. Continuous glucose monitoring measures glucose excursions during different meals and at different times of the day. End of dosing: Day 7 for MEDI0382 100 μg; Day 14 for MEDI0382 200 μg; and Day 28 for MEDI0382 300 μg.

An ITT population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to their randomized treatment group. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Posted

Mean

Standard Deviation

hr.mg/dL

Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Secondary

Change From Baseline in Mean 24-hrs Plasma Glucose to the End of Each Dosing Level as Measured by CGM

Posted

Mean

Standard Deviation

mg/dL

Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Secondary

Change From Baseline in Standard Deviation of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM

Posted

Mean

Standard Deviation

mg/dL

Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Secondary

Change From Baseline in Coefficient of Variation of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM

Posted

Mean

Standard Deviation

Percent of coefficient of variation

Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Secondary

Change From Baseline in Mean Amplitude of Glucose Excursions (MAGE) of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM

Posted

Mean

Standard Deviation

mg/dL

Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Secondary

Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Euglycemic Range to the End of Each Dosing as Measured by CGM

Posted

Mean

Standard Deviation

Percent of Euglycemic Range

Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Secondary

Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Hyperglycemic Range to the End of Each Dosing as Measured by CGM

Posted

Mean

Standard Deviation

Percent of hyperglycemic range

Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Secondary

Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Hypoglycemic Range to the End of Each Dosing as Measured by CGM

Posted

Mean

Standard Deviation

Percent of hypoglycemic range

Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Secondary

Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within Clinically Significant Hypoglycemic Range to the End of Each Dosing as Measured by CGM

Posted

Mean

Standard Deviation

Percent of hypoglycemic range

Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

ID	Title	Description
OG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
OG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Tachycardia	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected24 at risk EG0013 events1 affected25 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0015 events3 affected25 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0013 events3 affected25 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected24 at risk EG0011 events1 affected25 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0004 events2 affected24 at risk EG0017 events5 affected25 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0016 events5 affected25 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected24 at risk EG0013 events3 affected25 at risk
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0015 events5 affected25 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected24 at risk EG0010 events0 affected25 at risk
Palpitations	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0013 events1 affected25 at risk
Tachycardia paroxysmal	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk
Ear discomfort	Ear and labyrinth disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0012 events1 affected25 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0011 events1 affected25 at risk
Injection site erythema	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk
Bronchitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk
Gastroenteritis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk
Genital infection fungal	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk
Oral herpes	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk
Otitis media	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected24 at risk EG0010 events0 affected25 at risk
Procedural nausea	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0011 events1 affected25 at risk
Food craving	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected24 at risk EG0010 events0 affected25 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0011 events1 affected25 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk
Dizziness	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0013 events2 affected25 at risk
Balanoposthitis	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk
Pruritus genital	Reproductive system and breast disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected24 at risk EG0011 events1 affected25 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected24 at risk EG0010 events0 affected25 at risk

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals

ID	Title	Description
BG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
BG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
BG002	TOTAL	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	0	24	0	24	14	24
EG001	MEDI0382	Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	0	25	0	25	13	25