Back to resultsA Study to Evaluate the Safety and Tolerability of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
MEDI0382
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring MEDI0382, diabetes, obesity, overweight, type 2 diabetes mellitus
Eligibility Criteria
Inclusion Criteria:
- Participants aged 18 to 74 years (inclusive) at screening.
- Provision of signed and dated written informed consent (with the exception of consent for genetic and non-genetic research) prior to any study specific procedures.
- Body mass index (BMI) between 27 and 35 kg/m^2 (inclusive) at screening.
- Hemoglobin A1c (HbA1c) range of 6.5% to 8.5% (inclusive) at screening (Note: Participants may be re-tested for the HbA1c entry criterion only once.).
- Willing and able to self-inject study drug for the duration of the study.
- Diagnosed with type 2 diabetes mellitus with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease >= 500 mg/day) has occurred in the three months prior to screening.
- Female participants must have a negative pregnancy test at screening and randomization, and must not be lactating.
- Female participants of childbearing potential who are sexually active with a male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose of study drug.
Exclusion Criteria:
- History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the study drug, 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 during the run-in period.
- Any participant who has received another study drug as part of a clinical study or a glucagon-like peptide-1 (GLP-1) analogue containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening.
- Concurrent participation in another study of any kind and repeat randomization in this study is prohibited.
Any participant who has received any of the following medications prior to the start of the study:
- Herbal preparations or drugs licensed for control of body weight or appetite
- Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying
- Antimicrobials within the quinolone, macrolide or azole class
- Any change in antihypertensive medication
- Aspirin (acetylsalicylic acid)
- Paracetamol (acetaminophen) or paracetamol-containing preparations
- Ascorbic acid (vitamin C) supplements
- Severe allergy/hypersensitivity to any of the proposed study treatments, standardized meals, or excipients.
- 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 participant has been treated with daily SC insulin within 90 days prior to screening.
- Acute pancreatitis, pancreatic amylase, and/or pancreatic lipase > 3 × upper limit of normal range (ULN); history of chronic pancreatitis; or serum triglyceride levels > 11 mmol/L (1000 mg/dL) at screening.
- Significant inflammatory bowel disease, gastroparesis or other severe disease or surgery affecting the upper gastrointestinal 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 (NASH) or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results at screening:
- Aspartate transaminase (AST) >= 3 × ULN
- Alanine transaminase (ALT) >= 3 × ULN
- Total bilirubin (TBL) >= 2 × ULN
- Impaired renal function defined as estimated glomerular filtration rate (GFR) < 60 mL/minute/1.73m^2 at screening.
Poorly controlled hypertension defined as:
- Systolic blood pressure (BP) > 160 mm Hg
- Diastolic BP or >= 90 mm Hg
- Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead ECG or any abnormalities that may interfere with the interpretation of serial ECG changes.
- Prolonged QT intervals corrected for heart rate or family history of long QT-segment at screening.
- PR (PQ) interval prolongation, intermittent second or third-degree atrioventricular (AV) block, or AV dissociation.
- Persistent or intermittent complete bundle branch block.
- 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.
- 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 or any other condition known to interfere with the 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, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
- History of substance dependence, alcohol abuse, or excessive alcohol intake. Participants who use benzodiazepines for chronic anxiety or sleep disorders may be permitted to enter the study.
- Symptoms of depression or any other psychiatric disorder requiring treatment with medication.
- History of severe allergy/hypersensitivity, including to any component of the investigational product formulation or other biological agent, or ongoing clinically important allergy/hypersensitivity.
- Blood/plasma donation within 1 month of screening.
Sites / Locations
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
MEDI0382 Cohort 1
Placebo Cohort 1
MEDI0382 Cohort 2
Placebo Cohort 2
Arm Description
Participants will receive subcutaneous (SC) dose of MEDI0382 uptitrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week treatment extension period (TEP).
Participants will receive SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the uptitration period and thereafter once daily through 3 week TEP.
Participants will receive SC dose of MEDI0382 uptitrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Participants will receive SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period
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.
Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period
Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.
Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period
Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period
Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examinations findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and, endocrine.
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period
Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examination findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and endocrine.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.
Secondary Outcome Measures
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382
Area under the plasma concentration time curve over a dosing duration (AUCτ) of MEDI0382 is reported.
Maximum Observed Serum Concentration (Cmax) of MEDI0382
Maximum observed serum concentration (Cmax) of MEDI0382 is reported.
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382
Time to observed maximum serum concentration (Tmax) of MEDI0382 is reported.
Trough Plasma Concentration (Ctrough) of MEDI0382
Trough concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration (Ctrough) of MEDI0382 is reported.
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC
The Ro was calculated using the AUC method which account for the overall exposure measured using the Day 1 and specified time point (Day I). Ro = AUCtrough [Day I]/AUCtrough [Day 1]; where I is the specified day.
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment
Number of participants with positive ADA to MEDI0382 are reported.
Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time 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. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. During 14 days follow-up (Day 91), last observation carried forward (LOCF) approach was used to calculate the value.
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by 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. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level.
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM
Change from baseline in percentage of glucose AUC4Hrs during a standardized breakfast, lunch, and evening meal over time is reported. Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level.
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by 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. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Change from baseline in coefficient of variation in glucose over 7 days is reported.
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by 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. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Hyperglycemia (> 140 mg/dL), normoglycemia (70 -140 mg/dL), and clinically significant hypoglycemia (< 54 mg/dL).
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by 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. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Hyperglycemia (> 140 mg/dL), normoglycemia (70 -140 mg/dL), and clinically significant hypoglycemia (< 54 mg/dL).
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time
Change from baseline in estimated HbA1c based on 7-day glucose over time is reported.
Change From Baseline in Fasting Plasma Glucose Over Time
Change from baseline in fasting plasma glucose over time is reported. During the Day 21, and Day 28, LOCF approach was used to calculate the value.
Change From Baseline in HbA1c
Change from baseline in HbA1c is reported.
Absolute Change From Baseline in Body Weight
Absolute change from baseline in body weight is reported.
Percentage Change From Baseline in Body Weight
Percentage change from baseline in body weight is reported.
Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period
Absolute change from baseline in body weight to the end of each week of the up-titration period is reported.
Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period
Percentage change from baseline in body weight to the end of each week of the up-titration period is reported.
Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period
Percentage of participants achieving greater than 5% body weight loss from baseline is reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03745937
Brief Title
A Study to Evaluate the Safety and Tolerability of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus
Official Title
A Phase 2a Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of MEDI0382 in Overweight/Obese Subjects With Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
January 7, 2019 (Actual)
Primary Completion Date
May 28, 2019 (Actual)
Study Completion Date
May 28, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 2a, randomized, blinded, placebo-controlled study in up to 20 overweight or obese participants with type 2 diabetes mellitus. The participants will participate in the study for approximately 18 weeks, including screening, run-in and treatment periods and a safety follow-up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
MEDI0382, diabetes, obesity, overweight, type 2 diabetes mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MEDI0382 Cohort 1
Arm Type
Experimental
Arm Description
Participants will receive subcutaneous (SC) dose of MEDI0382 uptitrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week treatment extension period (TEP).
Arm Title
Placebo Cohort 1
Arm Type
Placebo Comparator
Arm Description
Participants will receive SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the uptitration period and thereafter once daily through 3 week TEP.
Arm Title
MEDI0382 Cohort 2
Arm Type
Experimental
Arm Description
Participants will receive SC dose of MEDI0382 uptitrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.
Arm Title
Placebo Cohort 2
Arm Type
Placebo Comparator
Arm Description
Participants will receive SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.
Intervention Type
Drug
Intervention Name(s)
MEDI0382
Intervention Description
Subcutaneous dose of MEDI0382 will be up-titrated weekly once daily up to 8 weeks during the uptitration period and thereafter once daily in 3-week TEP.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subcutaneous dose of placebo matched to MEDI0382 will be administered once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period
Description
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.
Time Frame
Baseline (Day -1) through Day 56 (end of Up-titration period)
Title
Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period
Description
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time Frame
Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Title
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period
Description
Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.
Time Frame
Baseline (Day -1) through Day 56 (end of Up-titration period)
Title
Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period
Description
Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.
Time Frame
Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Title
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period
Description
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).
Time Frame
Baseline (Day -1) through Day 56 (end of Up-titration period)
Title
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period
Description
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).
Time Frame
Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Title
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period
Description
Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examinations findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and, endocrine.
Time Frame
Baseline (Day -1) through Day 56 (end of Up-titration period)
Title
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period
Description
Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examination findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and endocrine.
Time Frame
Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Title
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period
Description
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.
Time Frame
Baseline (Day -1) through Day 56 (end of Up-titration period)
Title
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period
Description
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.
Time Frame
Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Secondary Outcome Measure Information:
Title
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382
Description
Area under the plasma concentration time curve over a dosing duration (AUCτ) of MEDI0382 is reported.
Time Frame
Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84
Title
Maximum Observed Serum Concentration (Cmax) of MEDI0382
Description
Maximum observed serum concentration (Cmax) of MEDI0382 is reported.
Time Frame
Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84
Title
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382
Description
Time to observed maximum serum concentration (Tmax) of MEDI0382 is reported.
Time Frame
Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84
Title
Trough Plasma Concentration (Ctrough) of MEDI0382
Description
Trough concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration (Ctrough) of MEDI0382 is reported.
Time Frame
Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84
Title
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC
Description
The Ro was calculated using the AUC method which account for the overall exposure measured using the Day 1 and specified time point (Day I). Ro = AUCtrough [Day I]/AUCtrough [Day 1]; where I is the specified day.
Time Frame
Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84
Title
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment
Description
Number of participants with positive ADA to MEDI0382 are reported.
Time Frame
Pre-dose (Day -2), Days 7, 14, 35, 42, 56; Day 21 of 3 week treatment extension, and 28 days post last dose (approximately 5 months)
Title
Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM)
Description
Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. During 14 days follow-up (Day 91), last observation carried forward (LOCF) approach was used to calculate the value.
Time Frame
Baseline (Day -1) through Day 56 (end of the up-titration period), Day 77 (end of the treatment extension period) and Day 91 (end of the follow-up period)
Title
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM
Description
Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level.
Time Frame
Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period
Title
Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM
Description
Change from baseline in percentage of glucose AUC4Hrs during a standardized breakfast, lunch, and evening meal over time is reported. Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level.
Time Frame
Baseline (Day -1) through Day 7 (end of Week 1), Day 56 (end of the up-titration period), and Day 77 (end of the treatment extension period)
Title
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM
Description
Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Change from baseline in coefficient of variation in glucose over 7 days is reported.
Time Frame
Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period
Title
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM
Description
Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Hyperglycemia (> 140 mg/dL), normoglycemia (70 -140 mg/dL), and clinically significant hypoglycemia (< 54 mg/dL).
Time Frame
Baseline (Day -1), Days 7, 14, 21, 28, 35, 42, 49, 56 of the up-titration period, and Day77 (end of the treatment extension period)
Title
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM
Description
Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Hyperglycemia (> 140 mg/dL), normoglycemia (70 -140 mg/dL), and clinically significant hypoglycemia (< 54 mg/dL).
Time Frame
Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period
Title
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time
Description
Change from baseline in estimated HbA1c based on 7-day glucose over time is reported.
Time Frame
Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period
Title
Change From Baseline in Fasting Plasma Glucose Over Time
Description
Change from baseline in fasting plasma glucose over time is reported. During the Day 21, and Day 28, LOCF approach was used to calculate the value.
Time Frame
Baseline (Day -1), Days 7, 14, 21, 28, 35, 42, 49, 56 of the up-titration period, and Day77 (end of the treatment extension period)
Title
Change From Baseline in HbA1c
Description
Change from baseline in HbA1c is reported.
Time Frame
Baseline (Day -1) through Day 77 (end of the treatment extension period)
Title
Absolute Change From Baseline in Body Weight
Description
Absolute change from baseline in body weight is reported.
Time Frame
Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP)
Title
Percentage Change From Baseline in Body Weight
Description
Percentage change from baseline in body weight is reported.
Time Frame
Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP)
Title
Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period
Description
Absolute change from baseline in body weight to the end of each week of the up-titration period is reported.
Time Frame
Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56
Title
Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period
Description
Percentage change from baseline in body weight to the end of each week of the up-titration period is reported.
Time Frame
Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56
Title
Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period
Description
Percentage of participants achieving greater than 5% body weight loss from baseline is reported.
Time Frame
Baseline (Day -1) through Day 77 (end of the treatment extension period)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants aged 18 to 74 years (inclusive) at screening.
Provision of signed and dated written informed consent (with the exception of consent for genetic and non-genetic research) prior to any study specific procedures.
Body mass index (BMI) between 27 and 35 kg/m^2 (inclusive) at screening.
Hemoglobin A1c (HbA1c) range of 6.5% to 8.5% (inclusive) at screening (Note: Participants may be re-tested for the HbA1c entry criterion only once.).
Willing and able to self-inject study drug for the duration of the study.
Diagnosed with type 2 diabetes mellitus with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease >= 500 mg/day) has occurred in the three months prior to screening.
Female participants must have a negative pregnancy test at screening and randomization, and must not be lactating.
Female participants of childbearing potential who are sexually active with a male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose of study drug.
Exclusion Criteria:
History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the study drug, 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 during the run-in period.
Any participant who has received another study drug as part of a clinical study or a glucagon-like peptide-1 (GLP-1) analogue containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening.
Concurrent participation in another study of any kind and repeat randomization in this study is prohibited.
Any participant who has received any of the following medications prior to the start of the study:
Herbal preparations or drugs licensed for control of body weight or appetite
Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying
Antimicrobials within the quinolone, macrolide or azole class
Any change in antihypertensive medication
Aspirin (acetylsalicylic acid)
Paracetamol (acetaminophen) or paracetamol-containing preparations
Ascorbic acid (vitamin C) supplements
Severe allergy/hypersensitivity to any of the proposed study treatments, standardized meals, or excipients.
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 participant has been treated with daily SC insulin within 90 days prior to screening.
Acute pancreatitis, pancreatic amylase, and/or pancreatic lipase > 3 × upper limit of normal range (ULN); history of chronic pancreatitis; or serum triglyceride levels > 11 mmol/L (1000 mg/dL) at screening.
Significant inflammatory bowel disease, gastroparesis or other severe disease or surgery affecting the upper gastrointestinal 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 (NASH) or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results at screening:
Aspartate transaminase (AST) >= 3 × ULN
Alanine transaminase (ALT) >= 3 × ULN
Total bilirubin (TBL) >= 2 × ULN
Impaired renal function defined as estimated glomerular filtration rate (GFR) < 60 mL/minute/1.73m^2 at screening.
Poorly controlled hypertension defined as:
Systolic blood pressure (BP) > 160 mm Hg
Diastolic BP or >= 90 mm Hg
Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead ECG or any abnormalities that may interfere with the interpretation of serial ECG changes.
Prolonged QT intervals corrected for heart rate or family history of long QT-segment at screening.
PR (PQ) interval prolongation, intermittent second or third-degree atrioventricular (AV) block, or AV dissociation.
Persistent or intermittent complete bundle branch block.
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.
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 or any other condition known to interfere with the 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, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
History of substance dependence, alcohol abuse, or excessive alcohol intake. Participants who use benzodiazepines for chronic anxiety or sleep disorders may be permitted to enter the study.
Symptoms of depression or any other psychiatric disorder requiring treatment with medication.
History of severe allergy/hypersensitivity, including to any component of the investigational product formulation or other biological agent, or ongoing clinically important allergy/hypersensitivity.
Blood/plasma donation within 1 month of screening.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tim Heise, MD
Organizational Affiliation
Profil Institut für Stoffwechselforschung GmbH
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Neuss
ZIP/Postal Code
41460
Country
Germany
12. IPD Sharing Statement
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D5670C00030&attachmentIdentifier=d7d04e4c-35ff-4fcf-aaf5-702ceca70934&fileName=d5670c00030-csp-amendment-3-redacted.pdf&versionIdentifier=
Description
CSP redacted protocol
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D5670C00030&attachmentIdentifier=aa440ccc-99bd-4f76-949f-11807a0cbb85&fileName=d5670c00030-sap-ed-1-redacted.pdf&versionIdentifier=
Description
SAP redacted
Learn more about this trial
A Study to Evaluate the Safety and Tolerability of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus
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