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

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

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

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency
• Intervention / Treatment: Drug: MEDI0382

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • Research Site
  • München, Germany, 81241
    • Research Site
• New Zealand
  • Auckland, New Zealand, 1010
    • Research Site
  • Christchurch, New Zealand, 8011
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 27, 2017
• Primary Completion (ACTUAL): April 24, 2018
• Study Completion (ACTUAL): April 24, 2018

Study Registration Dates

• First Submitted: July 27, 2017
• First Submitted That Met QC Criteria: July 27, 2017
• First Posted (ACTUAL): August 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 1, 2018
• Last Update Submitted That Met QC Criteria: April 30, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Kidney Failure, Kidney Insufficiency, Renal Failure, Renal Insufficiency, MEDI0382
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: D5670C00008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No