Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MEDI0382 Formulation 2, MEDI0382 Formulation 3, MEDI0382 low dose, MEDI0382 high dose, Cotadutide, Cotadutide 100 micrograms, Cotadutide 300 micrograms, Cotadutide 600 micrograms
MEDI0382 · 17 trials · 15 indications
To assess safety and tolerability of Cotadutide. Occurrence of AEs and serious AEs, including AEs leading to dose reduction, and AEs of special interest.
To assess safety and tolerability of Cotadutide.
To assess safety and tolerability of Cotadutide.
To assess safety and tolerability of Cotadutide.
To assess the immunogenicity of Cotadutide
To assess the immunogenicity of cotadutide. Titers represent a dilution and are therefore unitless. Summary statistics are based on the maximum observed titer for each ADA positive subject within the time frame.
Percentage change in UACR of cotadutide at different dose levels compared to placebo after 14 weeks. Efficacy endpoints for cotadutide vs. semaglutide are exploratory and are therefore excluded.
The number and percentage of treatment emergent adverse events (TEAE) and serious adverse events (SAE) through the end of the follow-up 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.
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.
To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo
To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo
Evaluation of the absolute bioavailability (F) of the SC formulations by comparison of AUCsubcut/AUCIV
Assessment of pharmacokinetics and relative bioavailability of cotadutide solution for injection by measuring maximum observed concentration (cmax)
Pharmacokinetic parameters AUC0-t for cotadutide in the high concentration and low concentration regimens
To assess the safety and tolerability of Cotadutide
To assess the safety and tolerability of Cotadutide
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 as measured by digitial 12-lead ECG.
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital sign parameters (Systolic Blood Pressure, Diastolic Blood Pressure, Pulse, Respiration rate, body temperature).
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 enocrine.
To characterize the PK profile of Cotadutide
To characterize the PK profile of Cotadutide
To characterize the PK profile of Cotadutide
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 urinalysis.
To assess the safety and tolerability of Cotadutide
To assess the safety and tolerability of Cotadutide
To assess the safety and tolerability of Cotadutide
To assess the safety and tolerability of Cotadutide
To assess the safety and tolerability of Cotadutide
To assess the safety and tolerability of Cotadutide
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.
To evaluate bioequivalence between formulation 2 and formulation 3 of MEDI0382
To evaluate bioequivalence between formulation 2 and formulation 3 of MEDI0382.
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).
| Arm | Type | Description |
|---|---|---|
| Cotadutide 300μg | EXPERIMENTAL | - |
| Placebo 300μg | PLACEBO_COMPARATOR | - |
| Cotadutide 600μg | EXPERIMENTAL | - |
| Placebo 600μg | PLACEBO_COMPARATOR | - |
| Cotadutide 100 micrograms | EXPERIMENTAL | Cotadutide 100 micrograms administered subcutaneously |
| Cotadutide 300 micrograms | EXPERIMENTAL | Cotadutide 300 micrograms administered subcutaneously |
| Cotadutide 600 micrograms | EXPERIMENTAL | Cotadutide 600 micrograms administered subcutaneously |
| Placebo | PLACEBO_COMPARATOR | Placebo administered subcutaneously |
| Semaglutide | ACTIVE_COMPARATOR | Semaglutide 1.0 miligrams administered subcutaneously |
| MEDI0382 high dose | EXPERIMENTAL | MEDI0382 high dose administered subcutaneously |
| Placebo for MEDI0382 high dose | PLACEBO_COMPARATOR | Placebo for MEDI0382 high dose administered subcutaneously |
| MEDI0382 low dose | EXPERIMENTAL | MEDI0382 low dose administered subcutaneoously |
| Placebo for MEDI0382 low dose | PLACEBO_COMPARATOR | Placebo for MEDI0382 low dose administered subcutaneously |
| 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. |
| 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) |
| MEDI0382 low dose + Metformin | EXPERIMENTAL | Drug: MEDI0382 low dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) |
| MEDI0382 mid dose + Metformin | EXPERIMENTAL | Drug: MEDI0382 mid dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) |
| MEDI0382 high dose + Metformin | EXPERIMENTAL | Drug: MEDI0382 high dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) |
| Placebo + Metformin | PLACEBO_COMPARATOR | Drug: Placebo Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) |
| Liraglutide + Metformin | ACTIVE_COMPARATOR | Drug: Liraglutide Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) |
| Cotadutide solution for injection | EXPERIMENTAL | Period 1, subcutaneous injection of cotadutide solution Period 2, subcutaneous injection of cotadutide solution Period 3, subcutaneous injection of cotadutide solution |
| Cotadutide | EXPERIMENTAL | Those subjects who were randomized to cotadutide once daily SC will begin at 50 μg once daily, then up-titrated to 100 μg once daily a week later, after that up-titration will be done at 100 μg increment weekly, till to a maximum of 600 μg once daily. |
| 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. |
| Sequence 1 | EXPERIMENTAL | formulation 2 on Day 1 and formulation 3 on Day 10 |
| Sequence 2 | EXPERIMENTAL | formulation 3 on Day 1 and formulation 2 on Day 10 |
| 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 |
|---|---|---|
| Cotadutide | DRUG | Cotadutide administered subcutaneously once daily |
| Placebo | DRUG | Placebo administered subcutaneously once daily |
| Cotadutide 100 micrograms | DRUG | Cotadutide 100 micrograms administered subcutaneously |
| Cotadutide 300 micrograms | DRUG | Cotadutide 300 micrograms administered subcutaneously |
| Cotadutide 600 micrograms | DRUG | Cotadutide 600 micrograms administered subcutaneously |
| Semaglutide | DRUG | Semaglutide 1.0 miligrams administered subcutaneously |
| MEDI0382 high dose | DRUG | MEDI0382 high dose administered subcutaneously |
| Placebo for MEDI0382 high dose | DRUG | Placebo for MEDI0382 high dose administered subcutaneously |
| MEDI0382 low dose | DRUG | MEDI0382 low dose administered subcutaneously |
| Placebo for MEDI0382 low dose | DRUG | Placebo for MEDI0382 low dose administered subcutaneously |
| 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. |
| 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). |
| MEDI0382 mid dose | DRUG | Pharmaceutical form: solution Route of administration: subcutaneous |
| cotadutide solution for injection | DRUG | cotadutide solution for injection |
| Experimental: Cotadutide | DRUG | Cotadutide: subcutaneous (SC) injection |
| MEDI0382 Formulation 2 | DRUG | Sequence 1 Period 1 and Sequence 2 Period 2. |
| MEDI0382 Formulation 3 | DRUG | Sequence 1 Period 2 and Sequence 2 Period 1 |
Inclusion Criteria: 1. Provision of informed consent 2. Males and female participants ≥ 18 to ≤ 75 years of age (inclusive) at the time of signing the informed consent. 3. Histologically confirmed non-alcoholic steatohepatitis (NASH) per NASH Clinical Research Network (CRN) criteria as diagnosed by...
MEDI0382 is an investigational small molecule developed by AstraZeneca PLC for metabolic conditions. It has been studied in non-alcoholic fatty liver disease, obesity, renal insufficiency, and type 2 diabetes mellitus. All seven of its clinical trials are completed, and the program reached Phase 2 development.
MEDI0382 has been studied for non-alcoholic fatty liver disease, including NASH, obesity, renal insufficiency, and type 2 diabetes mellitus. Clinical trials enrolled participants with NAFLD, overweight or obese participants with type 2 diabetes, and non-diabetic obese participants. It remains an investigational agent rather than an approved treatment.
MEDI0382 is developed by AstraZeneca PLC, which trades under the ticker AZN. The company sponsored the clinical program evaluating the drug across metabolic indications including type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease.
MEDI0382 reached Phase 2 clinical development. Seven trials have been conducted in total, all of which are completed, with no active trials ongoing. The program included Phase 1 and Phase 2 studies and enrolled 1,156 participants overall.
MEDI0382 has completed seven trials, including NCT04019561 in obese subjects with NAFLD/NASH, NCT03745937 in overweight and obese participants with type 2 diabetes, NCT03625778 in non-diabetic obese participants, and NCT03596177 examining energy balance in overweight and obese participants with type 2 diabetes.
Yes. MEDI0382 Formulation 2, MEDI0382 Formulation 3, MEDI0382 50 ug, MEDI0382 low dose, and MEDI0382 high dose are alternative names referring to the same AstraZeneca compound. These labels describe different formulations or dose levels studied within the same clinical development program.