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A Phase 2 study with two cohorts of differing doses designed to evaluate the efficacy, safety and pharmacokinetics (PK) of MEDI0382 in patients with Type 2 Diabetes Mellitus (T2DM). Approximately 63 subjects will be enrolled across two cohorts.
This is a randomised, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics of different doses of MEDI0382 administered as multiple SC doses to subjects with T2DM. Approximately 63 subjects will be enrolled across two cohorts.
For cohort 1, sufficient subjects will be invited to participate in the study such that a maximum of 39 subjects will complete dosing. Subjects in cohort 1 will be randomised using a ratio of 2:1 to one of 2 treatment arms to receive either MEDI0382 or placebo. A maximum of 26 will complete dosing in the active arm and 13 will complete dosing in the placebo arm.
For cohort 2, sufficient subjects will be invited to participate in the study such that a maximum of 24 subjects will complete dosing. Subjects in cohort 2 will be randomised using a ratio of 3:1 to receive either MEDI0382 or placebo. A maximum of 18 will complete dosing in the active arm and 6 will complete dosing in the placebo arm.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo Cohort 1 | Placebo Comparator | Participants will receive placebo matching with MEDI0382 subcutaneously once daily for 49 days. |
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| MEDI0382 Cohort 1 | Experimental | Participants will receive subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days |
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| PLacebo Cohort 2 | Placebo Comparator | Participants will receive placebo matching with MEDI0382 subcutaneously once daily for 49 days. |
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| MEDI0382 Cohort 2 | Experimental | Participants will receive subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MEDI0382 | Drug | MEDI0382 will be administered subcutaneously once daily for 49 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cohort 1: Percent Change From Baseline in Plasma Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours (AUC0-4h) by Mixed-meal Tolerance Test (MMTT) to Day 49 | The MMTT test involved the consumption of a standardised liquid meal within 5 minutes and timed serial blood samples obtained for the measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardised meal (with no additional food intake during this time). The percent change in the MMTT plasma glucose AUC 0-4h from the baseline (Day -1) to Day 49 is reported. | Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal |
| Cohort 1: Percent Change From Baseline in Body Weight to Day 50 | The percent change in body weight from baseline to Day 50 is reported. | Day 1 through Day 50 |
| Measure | Description | Time Frame |
|---|---|---|
| Cohort 1: Change From Baseline in Glycated Haemoglobin (HbA1c) to Day 49 | The change from baseline in Glycated haemoglobin (HbA1c) to Day 49 is reported. | Baseline (Day -1) through Day 49 |
| Cohort 1: Change From Baseline in Fasting Plasma Glucose to Day 49 |
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Inclusion Criteria:
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 subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures
Concurrent participation in another study of any kind and repeat randomisation in this study is prohibited
Severe allergy/hypersensitivity to any of the proposed study treatments
Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the subject has been treated with daily SC insulin within 90 days prior to screening
Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper 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 non-alcoholic steatohepatitis or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening:
Impaired renal function defined as estimated glomerular filtration rate (GFR) < 60 mL/minute/1.73 m2 at screening (GFR estimated according to Modification of Diet in Renal Disease [MDRD] using the isotope dilution mass spectrometry [IDMS] traceable MDRD Study Equation [SI units])
Poorly controlled hypertension defined as:
Unstable angina pectoris, myocardial infarction, transient ischemic attack or stroke within 3 months prior to screening, or subjects 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 or IV)
Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia
Haemoglobinopathy, haemolytic anemia, or chronic anaemia (haemoglobin concentration < 11.5 g/dL [115 g/L] for males, < 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, squamous cell skin cancer, or in situ cervical cancer
Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody
History of substance dependence, alcohol abuse, or excessive alcohol intake (defined as an average weekly intake of > 21 alcoholic drinks for men or > 10 alcoholic drinks for women) within 3 years prior to screening, and/or a positive screen for drugs of abuse or alcohol at screening or on admission to the study unit. Subjects who use tricyclic antidepressants or benzodiazepines for an established clinical indication may be permitted to enter the study based upon the judgement of the investigator.
Involvement of any AstraZeneca, MedImmune, contract research organization, or study site employee or their close relatives
History of acute or chronic pancreatitis or other diseases of the pancreas
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| Name | Affiliation | Role |
|---|---|---|
| Tim Heise, MD | Profil Institut für Stoffwechselforschung GmbH | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Berlin | 10117 | Germany | |||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40665896 | Derived | Bosch R, Petrone M, Arends R, Sijbrands EJG, Hoefman S, Snelder N. From In Vitro Efficacy to Long-Term HbA1c Response for GLP-1R/GlucagonR Agonism Using the 4GI-HbA1c Systems Model. CPT Pharmacometrics Syst Pharmacol. 2025 Sep;14(9):1515-1525. doi: 10.1002/psp4.70074. Epub 2025 Jul 16. | |
| 31608926 | Derived | Parker VER, Robertson D, Wang T, Hornigold DC, Petrone M, Cooper AT, Posch MG, Heise T, Plum-Moerschel L, Schlichthaar H, Klaus B, Ambery PD, Meier JJ, Hirshberg B. Efficacy, Safety, and Mechanistic Insights of Cotadutide, a Dual Receptor Glucagon-Like Peptide-1 and Glucagon Agonist. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgz047. doi: 10.1210/clinem/dgz047. |
| Label | URL |
|---|---|
| D5670C00011\_protocol\_amendment\_2\_ct | View source |
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A total of 120 participants consented to participate in the study. Of which 55 were screen failures; 65 participants were randomised (46 to MEDI0382 and 19 to placebo).
The study was conducted across 5 sites in Germany between 04Sep2017 and 23Jan2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo Cohort 1 | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. |
| FG001 | MEDI0382 Cohort 1 | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| FG002 | Placebo Cohort 2 | Participants received placebo matching with MEDI0382 SC once daily for 49 days. |
| FG003 | MEDI0382 Cohort 2 | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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As-treated population included all participants who received any study drug and were analyzed according to the treatment they received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo Cohort 1 | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. |
| BG001 | MEDI0382 Cohort 1 | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Cohort 1: Percent Change From Baseline in Plasma Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours (AUC0-4h) by Mixed-meal Tolerance Test (MMTT) to Day 49 | The MMTT test involved the consumption of a standardised liquid meal within 5 minutes and timed serial blood samples obtained for the measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardised meal (with no additional food intake during this time). The percent change in the MMTT plasma glucose AUC 0-4h from the baseline (Day -1) to Day 49 is reported. | Pharmacodynamic (PD) population included all participants who received at least one dose of study drug and had at least one post-baseline MMTT PD sample or PD evaluation. | Posted | Least Squares Mean | 95% Confidence Interval | Percent change | Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal |
|
From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo Cohort 1 | Participants received placebo matching with MEDI0382 subcutaneously (SC) once daily for 49 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Victoria Parker | MedImmune Limited | +44 747 1357152 | information.center@astrazeneca.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 17, 2017 | Jan 22, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 8, 2017 | Jan 22, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C000624433 | cotadutide |
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| Placebo | Drug | Placebo will be administered subcutaneously once daily for 49 days. |
|
The changes in the fasting plasma glucose level during the study period from baseline to Day 49 is reported. |
| Baseline (Day -1) through Day 49 |
| Cohort 1: Change From Baseline in Body Weight to Day 50 | The changes in the body weight during the study period from baseline to Day 50 is reported. | Day 1 through Day 50 |
| Cohort 1: Percentage of Participants Achieving Greater Than or Equal to 5% Body Weight Loss From Baseline to Day 50 | Participants achieving greater than or equal to 5% body weight loss from baseline to Day 50 is reported. | Day 1 through Day 50 |
| Cohort 1 and Cohort 2: Percent Change From Baseline in MMTT Plasma Glucose AUC 0-4h to Day 7 | The MMTT test involved the consumption of a standardised liquid meal within 5 minutes and timed serial blood samples obtained for the measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardised meal (with no additional food intake during this time). The percent change in the MMTT plasma glucose AUC 0-4h from the baseline (Day -1) evaluation to Day 7 is reported. | Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal |
| Cohort 1 and Cohort 2: 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. An 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. Treatment-emergent are the events between first doses of study drug through 7 to 14 days after the last dose of study drug (approximately 64 days). | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
| Cohort 1 and Cohort 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs | Treatment-emergent adverse events observed in participants with clinically significant vital signs abnormalities are reported. Vital sign parameters included blood pressure, heart rate, body temperature, and respiration rate. | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
| Cohort 1 and Cohort 2: Number of Participants With Abnormal Electrocardiogram Reported as TEAEs | Treatment-emergent adverse events observed in participants with clinically significant ECG abnormalities are reported. | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
| Cohort 1 and Cohort 2: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator as medically significant was reported as an AE. Laboratory evaluations included haematology, serum chemistry, and urinalysis. | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
| Cohort 1 and Cohort 2: Number of Participants With Injection Site Erythema | The injection site reactions observed during study visits were reported. Injection site reactions included (but are not limited to) local erythema, pain, tenderness, induration, swelling, pruritus, ulceration, and pigmentation. | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
| Cohort 1: Area Under the Concentration-time Curve During the Dosing Interval (AUCt) of MEDI0382 | The area under the concentration-time curve during the dosing interval of MEDI0382 is reported. | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
| Cohort 2: Area Under the Concentration-time Curve During the Dosing Interval (AUCt) of MEDI0382 | The area under the concentration-time curve during the dosing interval of MEDI0382 is reported. | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
| Cohort 1: Maximum Observed Concentration (Cmax) of MEDI0382 | The maximum observed concentration of MEDI0382 is reported. | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
| Cohort 2: Maximum Observed Concentration (Cmax) of MEDI0382 | The maximum observed concentration of MEDI0382 is reported. | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
| Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of MEDI0382 | The time to reach the maximum observed concentration of MEDI0382 is reported. | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
| Cohort 2: Time to Reach Maximum Observed Concentration (Tmax) of MEDI0382 | The time to reach the maximum observed concentration of MEDI0382 is reported. | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
| Cohort 1: Terminal Half Life (t1/2) of MEDI0382 | The t1/2 is the time measured for the concentration to decrease by one half after the dose of MEDI0382. | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
| Cohort 2: Terminal Half Life (t1/2) of MEDI0382 | The t1/2 is the time measured for the concentration to decrease by one half after the dose of MEDI0382. | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
| Cohort 1: Accumulation Ratio (Racc) of MEDI0382 | The Racc was calculated using the AUC method which account for the overall exposure measured using the specified time points on Day 22 and Day 49. Racc was calculated using the formula, Racc of Day 49 = AUCt of Day 49/AUCt of Day 22. | Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
| Cohort 2: Accumulation Ratio of MEDI0382 | The Racc was calculated using the AUC method which account for the overall exposure measured using the specified time points on Day 1, Day 7 and Day 14. Racc was calculated using the formulas: Racc of Day 7 = AUCt of Day 7/AUCt of Day 1; Racc of Day 14 = AUCt of Day 14/AUCt of Day 1. | Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
| Cohort 1: Trough Plasma Concentration (Ctrough) of MEDI0382 | Trough plasma concentration is the measured concentration from the plasma concentration-time data at the end of a dosing interval at steady state. | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
| Cohort 2: Trough Plasma Concentration (Ctrough) of MEDI0382 | Trough plasma concentration is the measured concentration from the plasma concentration time data at the end of a dosing interval at steady state. | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
| Cohort 1 and Cohort 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 | Participants with positive serum antibodies to MEDI0382 are reported. | Baseline (Day 1), Day 29, Day 50, and Follow-up Visit 2 (28 days after the last dose [approximately 64 days]) |
| Magdeburg |
| 39120 |
| Germany |
| Research Site | Mainz | 55116 | Germany |
| Research Site | Neu-Ulm | 89231 | Germany |
| Research Site | Neuss | 41460 | Germany |
| D5670C00011\_Statistical\_Analysis\_Plan | View source |
| Withdrew treatment |
|
| BG002 | Placebo Cohort 2 | Participants received placebo matching with MEDI0382 SC once daily for 49 days. |
| BG003 | MEDI0382 Cohort 2 | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. |
| BG004 | TOTAL | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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Participants received placebo matching with MEDI0382 SC once daily for 49 days. |
| OG001 | MEDI0382 Cohort 1 | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. |
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| Primary | Cohort 1: Percent Change From Baseline in Body Weight to Day 50 | The percent change in body weight from baseline to Day 50 is reported. | Intent-to-treat (ITT) population included all participants who received any study drug and were analyzed according to their randomized treatment group. | Posted | Least Squares Mean | 95% Confidence Interval | Percent change | Day 1 through Day 50 |
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| Secondary | Cohort 1: Change From Baseline in Glycated Haemoglobin (HbA1c) to Day 49 | The change from baseline in Glycated haemoglobin (HbA1c) to Day 49 is reported. | The ITT population included all participants who received any study drug and were analyzed according to their randomized treatment group. | Posted | Least Squares Mean | 90% Confidence Interval | Percentage change | Baseline (Day -1) through Day 49 |
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| Secondary | Cohort 1: Change From Baseline in Fasting Plasma Glucose to Day 49 | The changes in the fasting plasma glucose level during the study period from baseline to Day 49 is reported. | The ITT population included all participants who received any study drug and were analyzed according to their randomized treatment group. | Posted | Least Squares Mean | 90% Confidence Interval | mg/dL | Baseline (Day -1) through Day 49 |
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| Secondary | Cohort 1: Change From Baseline in Body Weight to Day 50 | The changes in the body weight during the study period from baseline to Day 50 is reported. | The ITT population included all participants who received any study drug and were analyzed according to their randomized treatment group. | Posted | Least Squares Mean | 90% Confidence Interval | Kilogram | Day 1 through Day 50 |
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| Secondary | Cohort 1: Percentage of Participants Achieving Greater Than or Equal to 5% Body Weight Loss From Baseline to Day 50 | Participants achieving greater than or equal to 5% body weight loss from baseline to Day 50 is reported. | The ITT population included all participants who received any study drug and were analyzed according to their randomized treatment group. | Posted | Number | Percentage of Participants | Day 1 through Day 50 |
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| Secondary | Cohort 1 and Cohort 2: Percent Change From Baseline in MMTT Plasma Glucose AUC 0-4h to Day 7 | The MMTT test involved the consumption of a standardised liquid meal within 5 minutes and timed serial blood samples obtained for the measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardised meal (with no additional food intake during this time). The percent change in the MMTT plasma glucose AUC 0-4h from the baseline (Day -1) evaluation to Day 7 is reported. | The PD population included all participants who received at least one dose of study drug and had at least one post-baseline MMTT PD sample or PD evaluation. The number of participants analyzed at the specified time point for this outcome measure are reported. | Posted | Mean | Standard Deviation | Percent change | Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal |
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| Secondary | Cohort 1 and Cohort 2: 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. An 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. Treatment-emergent are the events between first doses of study drug through 7 to 14 days after the last dose of study drug (approximately 64 days). | As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. | Posted | Count of Participants | Participants | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
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| Secondary | Cohort 1 and Cohort 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs | Treatment-emergent adverse events observed in participants with clinically significant vital signs abnormalities are reported. Vital sign parameters included blood pressure, heart rate, body temperature, and respiration rate. | As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. | Posted | Count of Participants | Participants | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
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| Secondary | Cohort 1 and Cohort 2: Number of Participants With Abnormal Electrocardiogram Reported as TEAEs | Treatment-emergent adverse events observed in participants with clinically significant ECG abnormalities are reported. | As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. | Posted | Count of Participants | Participants | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
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| Secondary | Cohort 1 and Cohort 2: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs | An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator as medically significant was reported as an AE. Laboratory evaluations included haematology, serum chemistry, and urinalysis. | As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. | Posted | Count of Participants | Participants | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
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| Secondary | Cohort 1 and Cohort 2: Number of Participants With Injection Site Erythema | The injection site reactions observed during study visits were reported. Injection site reactions included (but are not limited to) local erythema, pain, tenderness, induration, swelling, pruritus, ulceration, and pigmentation. | As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. | Posted | Count of Participants | Participants | From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days) |
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| Secondary | Cohort 1: Area Under the Concentration-time Curve During the Dosing Interval (AUCt) of MEDI0382 | The area under the concentration-time curve during the dosing interval of MEDI0382 is reported. | Pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Geometric Mean | Full Range | ng*hr/mL | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
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| Secondary | Cohort 2: Area Under the Concentration-time Curve During the Dosing Interval (AUCt) of MEDI0382 | The area under the concentration-time curve during the dosing interval of MEDI0382 is reported. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Geometric Mean | Full Range | ng*hr/mL | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
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| Secondary | Cohort 1: Maximum Observed Concentration (Cmax) of MEDI0382 | The maximum observed concentration of MEDI0382 is reported. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Geometric Mean | Full Range | ng/mL | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
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| Secondary | Cohort 2: Maximum Observed Concentration (Cmax) of MEDI0382 | The maximum observed concentration of MEDI0382 is reported. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Geometric Mean | Full Range | ng/mL | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
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| Secondary | Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of MEDI0382 | The time to reach the maximum observed concentration of MEDI0382 is reported. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Median | Full Range | Hours | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
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| Secondary | Cohort 2: Time to Reach Maximum Observed Concentration (Tmax) of MEDI0382 | The time to reach the maximum observed concentration of MEDI0382 is reported. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Median | Full Range | Hours | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
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| Secondary | Cohort 1: Terminal Half Life (t1/2) of MEDI0382 | The t1/2 is the time measured for the concentration to decrease by one half after the dose of MEDI0382. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Geometric Mean | Full Range | Hours | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
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| Secondary | Cohort 2: Terminal Half Life (t1/2) of MEDI0382 | The t1/2 is the time measured for the concentration to decrease by one half after the dose of MEDI0382. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Geometric Mean | Full Range | Hours | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
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| Secondary | Cohort 1: Accumulation Ratio (Racc) of MEDI0382 | The Racc was calculated using the AUC method which account for the overall exposure measured using the specified time points on Day 22 and Day 49. Racc was calculated using the formula, Racc of Day 49 = AUCt of Day 49/AUCt of Day 22. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Geometric Mean | Full Range | Ratio | Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
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| Secondary | Cohort 2: Accumulation Ratio of MEDI0382 | The Racc was calculated using the AUC method which account for the overall exposure measured using the specified time points on Day 1, Day 7 and Day 14. Racc was calculated using the formulas: Racc of Day 7 = AUCt of Day 7/AUCt of Day 1; Racc of Day 14 = AUCt of Day 14/AUCt of Day 1. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Geometric Mean | Full Range | Ratio | Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
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| Secondary | Cohort 1: Trough Plasma Concentration (Ctrough) of MEDI0382 | Trough plasma concentration is the measured concentration from the plasma concentration-time data at the end of a dosing interval at steady state. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Geometric Mean | Full Range | ng/mL | Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49 |
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| Secondary | Cohort 2: Trough Plasma Concentration (Ctrough) of MEDI0382 | Trough plasma concentration is the measured concentration from the plasma concentration time data at the end of a dosing interval at steady state. | The PK population included all participants who received at least 1 dose of study drug and had at least 1 post-baseline PK sample with a value above lower limit of quantification. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Geometric Mean | Full Range | ng/mL | Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14 |
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| Secondary | Cohort 1 and Cohort 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 | Participants with positive serum antibodies to MEDI0382 are reported. | As-treated population included all participants who received any study drug and were analyzed according to the treatment they received. The "Number Analyzed" denotes the number of participants analyzed at the specified time point for this outcome measure. | Posted | Count of Participants | Participants | Baseline (Day 1), Day 29, Day 50, and Follow-up Visit 2 (28 days after the last dose [approximately 64 days]) |
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| 0 |
| 13 |
| 0 |
| 13 |
| 6 |
| 13 |
| EG001 | MEDI0382 Cohort 1 | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days. | 0 | 26 | 0 | 26 | 22 | 26 |
| EG002 | Placebo Cohort 2 | Participants received placebo matching with MEDI0382 SC once daily for 49 days. | 0 | 6 | 0 | 6 | 3 | 6 |
| EG003 | MEDI0382 Cohort 2 | Participants received subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days. | 0 | 20 | 0 | 20 | 15 | 20 |
| Tachycardia | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
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| Visual impairment | Eye disorders | MedDRA 20.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Abdominal wall haematoma | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Eructation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Parotid gland enlargement | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Regurgitation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Tongue discomfort | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Face oedema | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Induration | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Injection site haematoma | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Malaise | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Medical device site pain | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Medical device site swelling | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Vessel puncture site haematoma | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Nasal herpes | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
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| Procedural nausea | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Gout | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Loss of libido | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
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| Nocturia | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
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| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA 20.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Nasal obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Skin reaction | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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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.
| D004700 | Endocrine System Diseases |
| TESAEs |
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| Hypoglycaemia |
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| Day 14 |
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| Day 14 |
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| Day 14 |
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| Day 14 |
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| Day 14 |
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| Day 29 (ADA positive) |
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| Day 50 (ADA positive) |
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| Follow-up Visit 2 (ADA positive) |
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