A Study to Evaluate Pharmacokinetics, Safety and Tolerability of MEDI0382 in Renal Impairment Subjects
Primary Purpose
Renal Insufficiency
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MEDI0382
Sponsored by
About this trial
This is an interventional basic science trial for Renal Insufficiency focused on measuring Kidney Failure, Kidney Insufficiency, Renal Failure, Renal Insufficiency, MEDI0382
Eligibility Criteria
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Active Comparator
Experimental
Arm Label
Group 1: End Stage Renal Disease (ESRD)
Group 2: Severe and ESRD Subjects
Group 3: Healthy Subjects
Group 4: Moderate Renal Disease
Arm Description
Subjects with CrCl <20ml/min will receive MEDI0382 administered subcutaneously
Subjects with CrCl >20 and < 30 ml/min will receive MEDI0382 administered subcutaneously
Subjects with CrCl >90 ml/min will receive MEDI0382 administered subcutaneously
Subjects with CrCl > or equal to 30 and < 60 mL/min will receive MEDI0382 administered subcutaneously
Outcomes
Primary Outcome Measures
Maximum Observed Concentration of MEDI0382 (Cmax)
The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data
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
Secondary Outcome Measures
Time to maximum observed concentration (Tmax)
Time to maximum observed concentration.
apparent clearance (Cl/F)
The apparent clearance will be calculated as CL/F=Dose/AUC(0-inf)
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.
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
Anti-drug Antibody (ADA) titer
ADA titer through to day 28
Number of subjects with Adverse Events
Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs)
Number of subjects with Adverse Events
Vital Signs (systolic and diastolic blood pressure, pulse rate, temperature and respiratory rates)
Number of subjects with Adverse Events
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03235375
Brief Title
A Study to Evaluate Pharmacokinetics, Safety and Tolerability of MEDI0382 in Renal Impairment Subjects
Official Title
A Phase 1, Open-Label, Single Dose, Parallel-Group Study to Evaluate the Pharmacokinetics, Safety and Tolerability of MEDI0382 in Subjects With Renal Impairment
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
October 27, 2017 (Actual)
Primary Completion Date
April 24, 2018 (Actual)
Study Completion Date
April 24, 2018 (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
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Insufficiency
Keywords
Kidney Failure, Kidney Insufficiency, Renal Failure, Renal Insufficiency, MEDI0382
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: End Stage Renal Disease (ESRD)
Arm Type
Experimental
Arm Description
Subjects with CrCl <20ml/min will receive MEDI0382 administered subcutaneously
Arm Title
Group 2: Severe and ESRD Subjects
Arm Type
Experimental
Arm Description
Subjects with CrCl >20 and < 30 ml/min will receive MEDI0382 administered subcutaneously
Arm Title
Group 3: Healthy Subjects
Arm Type
Active Comparator
Arm Description
Subjects with CrCl >90 ml/min will receive MEDI0382 administered subcutaneously
Arm Title
Group 4: Moderate Renal Disease
Arm Type
Experimental
Arm Description
Subjects with CrCl > or equal to 30 and < 60 mL/min will receive MEDI0382 administered subcutaneously
Intervention Type
Drug
Intervention Name(s)
MEDI0382
Intervention Description
MEDI0382 administered subcutaneously
Primary Outcome Measure Information:
Title
Maximum Observed Concentration of MEDI0382 (Cmax)
Description
The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data
Time Frame
0-48 hours
Title
Area under the Concentration Time Curve (AUC) of MEDI0382
Description
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
Time Frame
0-48 hours
Secondary Outcome Measure Information:
Title
Time to maximum observed concentration (Tmax)
Description
Time to maximum observed concentration.
Time Frame
0-48 hours
Title
apparent clearance (Cl/F)
Description
The apparent clearance will be calculated as CL/F=Dose/AUC(0-inf)
Time Frame
0-48 hours
Title
AUCinf
Description
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.
Time Frame
0-48 hours
Title
Half-life (T1/2)
Description
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
Time Frame
0-48 hours
Title
Anti-drug Antibody (ADA) titer
Description
ADA titer through to day 28
Time Frame
Day -1 to day 28
Title
Number of subjects with Adverse Events
Description
Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs)
Time Frame
Study onset till 28 days post dosing
Title
Number of subjects with Adverse Events
Description
Vital Signs (systolic and diastolic blood pressure, pulse rate, temperature and respiratory rates)
Time Frame
Study onset till 28 days post dosing
Title
Number of subjects with Adverse Events
Description
Clinical laboratory assessments (serum chemistry, hematology, and urinalysis)
Time Frame
Study onset till 28 days post dosing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Research Site
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Research Site
City
München
ZIP/Postal Code
81241
Country
Germany
Facility Name
Research Site
City
Auckland
ZIP/Postal Code
1010
Country
New Zealand
Facility Name
Research Site
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
12. IPD Sharing Statement
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A Study to Evaluate Pharmacokinetics, Safety and Tolerability of MEDI0382 in Renal Impairment Subjects
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