A Phase 1, Single- and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MEDI4166 in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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A Phase 1, combined Single Ascending Dose (SAD) and Multiple-ascending Dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MEDI4166 in Subjects with Type 2 Diabetes Mellitus (T2D).

Detailed Description
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This study is a first time in human (FTIH), Phase 1, randomized, double-blind study to evaluate the safety, tolerability, PK, and PD of MEDI4166 administered as both single and multiple ascending doses to subjects with T2D.

Official Title
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A Phase 1, Combined Single- and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of MEDI4166 in Subjects With Type 2 Diabetes Mellitus (T2D)

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Biological: MEDI-4166
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes, ages 18-65 Must provide written informed consent BMI>=25 and =<42 Venous access suitable for multiple cannulations Vital signs within normal specified ranges Females must be non-lactating and non-childbearing potential Males must practice 2 effective contraceptive measures if sexually active Exclusion Criteria: Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs History of cancer, with the exception of basal cell carcinoma or carcinoma of the cervix Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing Positive Hepatitis B, Hepatitis C or HIV test or use of antiretroviral medications at screening Current or previous use of systemic corticosteroids within the past 28 days prior to screening Use of any medicinal products or herbal preparations licensed for weight loss is prohibited. Positive drug screen Type 1 diabetes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI-4166<br>MEDI-4166 administered subcutaneously | Biological: MEDI-4166<br>* MEDI-4166 administered subcutaneously<br>|
| Placebo Comparator: Placebo<br>Placebo administered subcutaneously | Biological: Placebo<br>* Placebo administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166 | Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs) | 43 days post dosing | 
| Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166 | 12 lead electrocardiogram including RR, PR, QRS, QT and QTc intervals | 43 days post dosing | 
| Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166 | Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory rate) | 43 days post dosing | 
| Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166 | Clinical laboratory assessments (serum chemistry, hematology, urinalysis) | 43 days post dosing | 
| Part A: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166 | Physical examination | 43 days post dosing | 
| Part B: Change in glucose AUC measured up to 240 minutes after mixed meal tolerance test (MMTT) from baseline to Day 36 | Part B: Change in glucose AUC measured up to 240 minutes after mixed meal tolerance test (MMTT) from baseline to Day 36 | 36 days post dosing | 
| Part B: Change in LDL-C from baseline to Day 36 | Part B: Change in LDL-C from baseline to Day 36 | 36 days post dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Pharmacokinetics of MEDI4166, maximum plasma concentration (Cmax) | Part A: Pharmacokinetics of MEDI4166, maximum plasma concentration (Cmax) | 43 days post dosing | 
| Part A: Pharmacokinetics of MEDI4166, area under the curve concentration (AUC) | Part A: Pharmacokinetics of MEDI4166, area under the curve concentration (AUC) | 43 days post dosing | 
| Part A: Change from baseline in LDL-C | Part A: Change from baseline in LDL-C | 43 days post dosing | 
| Part A: Proportion of subjects with Anti-drug Antibodies (ADA) to MEDI4166 | Part A: Proportion of subjects with ADA to MEDI4166 | 43 days post dosing | 
| Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166 | Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs) | 71 days post dosing | 
| Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166 | 12 lead electrocardiogram including RR, PR, QRS, QT and QTc intervals | 71 days post dosing | 
| Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166 | Vital signs (systolic and diastolic blood pressure, pulse rate, temperature, and respiratory rate) | 71 days post dosing | 
| Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166 | Clinical laboratory assessments (serum chemistry, hematology, urinalysis) | 71 days post dosing | 
| Part B: Number of subjects with adverse events as a measure of safety and tolerability of MEDI4166 | Physical examination | 71 days post dosing | 
| Part B: Pharmacokinetics of MEDI4166, maximum plasma concentration (Cmax) | Part B: Pharmacokinetics of MEDI4166, maximum plasma concentration (Cmax) | 71 days post dosing | 
| Part B: Pharmacokinetics of MEDI4166, area under the curve concentration (AUC) | Part B: Pharmacokinetics of MEDI4166, area under the curve concentration (AUC) | 71 days post dosing | 
| Part B: Change from baseline in fructosamine levels | Part B: Change from baseline in fructosamine levels | 36 days post dosing | 
| Part B: Proportion of subjects with ADA to MEDI4166 | Part B: Proportion of subjects with ADA to MEDI4166 | 71 days post dosing | 
| Part A: Pharmacokinetics of MEDI4166, time to maximum observed plasma drug concentration (Tmax) | Part A: Pharmacokinetics of MEDI4166, time to maximum observed plasma drug concentration (Tmax) | 43 days post dosing | 
| Part A: Change from baseline in glucose AUC up to 240 minutes | Part A: Change from baseline in glucose AUC up to 240 minutes | 43 days post dosing | 
| Part B: Pharmacokinetics of MEDI4166, time to maximum observed plasma drug concentration (Tmax) | Part B: Pharmacokinetics of MEDI4166, time to maximum observed plasma drug concentration (Tmax) | 71 days post dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MEDI-4166, diabetes