Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
MEDI0382 · 12 trials · 8 indications
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.
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 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 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 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 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 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 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 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 are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.
Percent change in body weight from baseline to Day 59 is reported. Day 17 was considered as baseline for this outcome measure. The last observation carried forward (LOCF) analysis was used for missing data imputation for Day 59.
The MMTT involved the consumption of a standardised liquid meal (a nutritional supplement containing the components of fat, carbohydrate, and protein, which make up a standard MMTT) within 15 minutes, and timed serial blood samples obtained for measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardized meal (with no additional food intake during this time).
To assess the effect of MEDI0382 on hepatic glycogen levels postprandially versus placebo after 28 days of treatment
To assess the effect of MEDI0382 on hepatic glycogen levels versus placebo after 35 days (Part B) of treatment
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).
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).
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.
The percent change in body weight from baseline to Day 50 is reported.
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 abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters were defined as any abnormal finding during analysis of hematology, clinical chemistry, and urinalysis.
Number of participants with abnormal vital signs (body temperature, blood pressure, heart rate, and respiratory rate) and physical examinations reported as TEAEs are reported.
Number of participants with abnormal ECG parameters reported as TEAEs are reported.
Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in blood pressure from baseline to end of dosing measured by telemetry for Cohort 1 are reported.
Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in respiratory rate from baseline to end of dosing measured by telemetry for Cohort 1 are reported.
Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in pulse rate from baseline to end of dosing measured by telemetry for Cohort 1 are reported.
Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in temperature from baseline to end of dosing measured by telemetry for Cohort 1 are reported.
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. 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 and up to Day 29.
An AESI (serious or non-serious) was one of scientific and medical interest specific to understanding of study drug and may have required close monitoring and rapid communication by investigator to the sponsor.
Number of participants with TEAEs related to clinically significant ECG abnormalities are reported.
Number of participants with TEAEs related to vital sign abnormalities are reported.
Number of participants with TEAEs related to clinically significant abnormal laboratory parameter are reported.
To assess the INR max in the absence and presence of Warfarin on a steady state MEDI0382
To assess the effects of MEDI0382 on the hear rate-lowering effect of esmolol during treadmill test.
The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data
The area under the plasma concentration-time curve to 48 hours concentration determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hours (hrs) after consumption of the standardized meal (with no additional food intake during this time).
Treatment emergent adverse events (TEAEs) and serious adverse events (STEAEs)
| Arm | Type | Description |
|---|---|---|
| MEDI0382 Cohort 1 | EXPERIMENTAL | 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). |
| Placebo Cohort 1 | PLACEBO_COMPARATOR | 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. |
| MEDI0382 Cohort 2 | EXPERIMENTAL | 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. |
| Placebo Cohort 2 | PLACEBO_COMPARATOR | 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. |
| MEDI0382 | EXPERIMENTAL | Participants will receive subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period. |
| MEDI0382 (Part A) | EXPERIMENTAL | MEDI0382 administered subcutaneously (Part A) |
| Placebo (Part A) | PLACEBO_COMPARATOR | Placebo comparator administered subcutaneously (Part A) |
| Liraglutide (Part B) | ACTIVE_COMPARATOR | Active comparator administered subcutaneously (Part B) |
| MEDI0382 (Part B) | EXPERIMENTAL | MEDI0382 administered subcutaneously (Part B) |
| Placebo (Part B) | PLACEBO_COMPARATOR | Placebo comparator administered subcutaneously (Part B) |
| Placebo Cohort 3 | PLACEBO_COMPARATOR | Participants will receive SC placebo matched to MEDI0382 Cohort 3 once daily for 18 weeks. |
| MEDI0382 Cohort 3 | EXPERIMENTAL | Participants will receive SC MEDI0382 titrated doses of Doses 1, 8, 4, and 7 once daily (4-step titration/ 4 week per dose) from Weeks 1 to 16 followed by additional treatment of SC MEDI0382 Dose 7 once daily from Weeks 17 to 18. |
| Placebo Japanese Descent | PLACEBO_COMPARATOR | Participants of Japanese descent will receive a single subcutaneous injection of placebo matching to MEDI0382. |
| MEDI0382 50 mcg Japanese Descent | EXPERIMENTAL | Participants of Japanese descent will receive a single subcutaneous dose of 50 mcg MEDI0382. |
| MEDI0382 100 mcg Japanese Descent | EXPERIMENTAL | Participants of Japanese descent will receive a single subcutaneous dose of 100 mcg MEDI0382. |
| MEDI0382 150 mcg Japanese Descent | EXPERIMENTAL | Participants of Japanese descent will receive a single subcutaneous dose of 150 mcg MEDI0382. |
| Placebo Chinese Descent | EXPERIMENTAL | Participants of Chinese descent will receive a single subcutaneous injection of placebo matching to MEDI0382. |
| MEDI0382 100 mcg Chinese Descent | EXPERIMENTAL | Participants of Chinese descent will receive a single subcutaneous dose of 100 mcg MEDI0382. |
| Warfarin | ACTIVE_COMPARATOR | All participants will receive Warfarin |
| Esmolol | ACTIVE_COMPARATOR | All participants will receive Esmolol |
| Group 1: End Stage Renal Disease (ESRD) | EXPERIMENTAL | Subjects with CrCl \<20ml/min will receive MEDI0382 administered subcutaneously |
| Group 2: Severe and ESRD Subjects | EXPERIMENTAL | Subjects with CrCl \>20 and \< 30 ml/min will receive MEDI0382 administered subcutaneously |
| Group 3: Healthy Subjects | ACTIVE_COMPARATOR | Subjects with CrCl \>90 ml/min will receive MEDI0382 administered subcutaneously |
| Group 4: Moderate Renal Disease | EXPERIMENTAL | Subjects with CrCl \> or equal to 30 and \< 60 mL/min will receive MEDI0382 administered subcutaneously |
| Cohort 1: MEDI0382 100 mcg | EXPERIMENTAL | Participants will receive MEDI0382 100 mcg SC once daily from Day 1 to Day 7. |
| Cohort 2: MEDI0382 150 mcg | EXPERIMENTAL | Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). |
| Cohort 3: MEDI0382 200 mcg | EXPERIMENTAL | Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). |
| Cohort 4: MEDI0382 200 mcg | EXPERIMENTAL | Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). |
| Cohort 5: MEDI0382 300 mcg | EXPERIMENTAL | Participants will receive MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). |
| Cohort 6: MEDI0382 300 mcg | EXPERIMENTAL | Participants will receive MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). |
| Name | Type | Description |
|---|---|---|
| MEDI0382 | DRUG | 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. |
| Placebo | DRUG | 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. |
| Liraglutide | DRUG | Liraglutide administered subcutaneously |
| Dapaglifozin | DRUG | Oral dose of dapaglifozin 10 mg tablet. |
| Metformin | DRUG | Oral dose of metformin tablet (maximum tolerated dose \[MTD\] \> 1 g). |
| Warfarin | DRUG | All participants will receive Warfarin |
| Esmolol | DRUG | All participants will receive Esmolol |
Inclusion Criteria: 1. Participants aged 18 to 74 years (inclusive) at screening. 2. 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. 3. Body mass index (BMI) between 27 and 35 kg/m\^2...
MEDI0382 is an investigational small molecule being developed for metabolic conditions, including obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). It has been studied in overweight and obese participants with type 2 diabetes. MEDI0382 is not approved and remains in clinical development.
MEDI0382 is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker AZN. AstraZeneca is conducting clinical trials to evaluate the safety and efficacy of MEDI0382 in metabolic indications.
MEDI0382 is in Phase 2 clinical development. It has completed multiple Phase 2 trials, including studies in overweight and obese participants with type 2 diabetes. MEDI0382 is investigational and has not been approved by regulatory authorities.
MEDI0382 has completed several clinical trials, including NCT02548585, a Phase 1 multiple-ascending-dose study, and NCT03244800, NCT03444584, and NCT03745937, which are Phase 2 studies. These trials evaluated MEDI0382 in overweight and obese participants with type 2 diabetes, including in combination with dapagliflozin and metformin.
MEDI0382 is also referred to as 0382 in some clinical trial titles, such as NCT03244800, which investigates different doses of 0382. Both names refer to the same investigational drug being developed by AstraZeneca for metabolic conditions.