A Study to Evaluate Pharmacokinetics, Safety and Tolerability of MEDI0382 in Renal Impairment Subjects

Study Overview
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Brief Summary
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A phase 1 open-label, single-dose study to evaluate the pharmacokinetics (PK), safety, tolerability and immunogenicity of MEDI0382 in subjects with renal impairment.

Detailed Description
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This is an open-label, single-dose, parallel group study to evaluate the PK, safety, tolerability, and immunogenicity of MEDI0382 in subjects with renal impairment. Enrollment of approximately 40 subjects across multiple sites is planned. Subjects will be divided into 4 groups based on renal function.

Official Title
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A Phase 1, Open-Label, Single Dose, Parallel-Group Study to Evaluate the Pharmacokinetics, Safety and Tolerability of MEDI0382 in Subjects With Renal Impairment

Conditions
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Renal Insufficiency

Intervention / Treatment
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* Drug: MEDI0382


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must provide written informed consent BMI greater than or equal to 17 and less than or equal to 40 kg/m2 Creatinine clearance rate greater than or equal to 90 (healthy); or renally impaired (less than 60 mL/min) Females of childbearing potential must use a highly effective form of contraception. Exclusion Criteria: Any history of or concurrent condition that in the opinion of the investigator would compromise the subjects safety. Subjects on dialysis Subjects with pancreatitis Renal transplant subjects Females pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: End Stage Renal Disease (ESRD)<br>Subjects with CrCl <20ml/min will receive MEDI0382 administered subcutaneously | Drug: MEDI0382<br>* MEDI0382 administered subcutaneously<br>|
| Experimental: Group 2: Severe and ESRD Subjects<br>Subjects with CrCl >20 and < 30 ml/min will receive MEDI0382 administered subcutaneously | Drug: MEDI0382<br>* MEDI0382 administered subcutaneously<br>|
| Active Comparator: Group 3: Healthy Subjects<br>Subjects with CrCl >90 ml/min will receive MEDI0382 administered subcutaneously | Drug: MEDI0382<br>* MEDI0382 administered subcutaneously<br>|
| Experimental: Group 4: Moderate Renal Disease<br>Subjects with CrCl > or equal to 30 and < 60 mL/min will receive MEDI0382 administered subcutaneously | Drug: MEDI0382<br>* MEDI0382 administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration of MEDI0382 (Cmax) | The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data | 0-48 hours | 
| Area under the Concentration Time Curve (AUC) of MEDI0382 | 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 | 0-48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to maximum observed concentration (Tmax) | Time to maximum observed concentration. | 0-48 hours | 
| apparent clearance (Cl/F) | The apparent clearance will be calculated as CL/F=Dose/AUC(0-inf) | 0-48 hours | 
| AUCinf | The AUC extrapolated to infinity will be calculated, where data permit, as the sum of AUC((0-t) and Ct/z, where Ct is the observed plasma concentration obtained from the log-linear regression analysis of the last quantifiable time-point and z is the terminal phase rate constant. | 0-48 hours | 
| Half-life (T1/2) | The apparent terminal elimination half-life (t1/2) obtained as the ratio of ln2/z, where z is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data | 0-48 hours | 
| Anti-drug Antibody (ADA) titer | ADA titer through to day 28 | Day -1 to day 28 | 
| Number of subjects with Adverse Events | Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs) | Study onset till 28 days post dosing | 
| Number of subjects with Adverse Events | Vital Signs (systolic and diastolic blood pressure, pulse rate, temperature and respiratory rates) | Study onset till 28 days post dosing | 
| Number of subjects with Adverse Events | Clinical laboratory assessments (serum chemistry, hematology, and urinalysis) | Study onset till 28 days post dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Failure, Kidney Insufficiency, Renal Failure, Renal Insufficiency, MEDI0382