Pharmacokinetics and Safety of POL7080 in Patients With Renal Impairment

An Open-label, Non-randomized, Monocenter, Single-dose, Phase I Study to Evaluate Pharmacokinetics and Safety of POL7080 Administered as Single Intravenous Infusion to Subjects With Renal Impairment

To investigate the pharmacokinetics (PK) of POL7080 in subjects with renal function impairment after single intravenous (IV) infusion of POL7080

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: POL7080

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • CRS Clinical Research Services Kiel GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects who signed informed consent.
2. Male subjects ≥18 and ≤79 years of age; female subjects ≥18 and ≤79 years of age of non-childbearing potential
3. Weight within a BMI range of 19.0-35.0 kg/m2.

4. CLCr according to Cockcroft Gault equation of:

   • 50-80 mL/min (mild renal impairment)
   • 30- <50 mL/min (moderate renal impairment)
   • <30 mL/min (severe renal impairment)
   • subjects receiving dialysis for ≥3 months before dosing (ESRD)
   • >80 mL/min (normal renal function)

Exclusion Criteria:

1. Unwilling or unable to give informed consent.
2. As a result of the medical screening process, the study physician considers the subject unfit for the study.
3. Demonstrating excess in xanthine consumption (more than 5 cups of coffee or equivalent per day).
4. Subjects who smoke more than 10 cigarettes a day.
5. Subjects who consume more than 28 units (males) or more than 21 units (females) of alcohol per week.
6. Any history of hypersensitivity to the IMP.
7. For subjects with renal impairment: No clinically significant change in disease status within at least 1 month prior to study entry, as determined by the investigator.
8. The subject had donated a unit of blood (450 mL) within the 3 months before dosing, or intends to donate in the month after the last scheduled visit.
9. Participation in another clinical study with an investigational drug or device within the last month.
10. Subjects with clinically significant telemetric ECG abnormalities on Day -1
11. Significant allergies requiring intranasal or systemic corticosteroids during any time of the year or history of any anaphylactic reaction.
12. Positive test for human immunodeficiency virus (HIV) antibodies.
13. Acute Hepatitis B or C infection.
14. The subject has tested positive for drugs of abuse at screening.
15. Subjects who have received any prescribed systemic or topical medication within 4 weeks prior to dosing (excluded are those drugs the renally impaired subject is currently taking for treatment of the renal or concomitant disease).
16. Immunocompromised patients (patients after solid organ or bone marrow transplant; patients receiving immunosuppressive treatment).
17. Subjects with known or suspected Pseudomonas infection or colonization (e.g. patients with cystic fibrosis).
18. Subjects with significant liver function abnormalities
19. Subjects with acute myocardial infection or unstable angina pectoris

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild renal impairment; 3h IV POL7080 infusion	Drug: POL7080; Intravenous infusion
Experimental: Moderate renal impairment; 3h IV POL7080 infusion	Drug: POL7080; Intravenous infusion
Experimental: Severe renal impairment; 3h IV POL7080 infusion	Drug: POL7080; Intravenous infusion
Experimental: End stage renal disease arm 1; 3h IV POL7080 infusion	Drug: POL7080; Intravenous infusion
Experimental: End stage renal disease arm 2; 3h IV POL7080 infusion	Drug: POL7080; Intravenous infusion
Experimental: Normal Renal function; 3h IV POL7080 infusion	Drug: POL7080; Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To measure the plasma concentrations of POL7080	at baseline, 0.5, 1,1.5 and 3 hours after start of infusion, at 1, 2, 3, 4, 5, 6, 8, 12, 24, 48 and 72 hours after end of infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of adverse events reported by the patients or observed by the investigator will be recorded. Onset, end date, severity, causal relationship, outcome and measures taken will be summarized. Discontinuations and serious adverse events will be listed and narrative summaries will be provided.	Daily assessment up to 7 days from informed consent
Laboratory abnormalities	The number and severity of blood chemistry and hematology findings will be summarized descriptively and compared to baseline.	Screening, Day -1, Day 2, Day 3, and Day 7

Collaborators and Investigators

• Sponsor: Polyphor Ltd.

Publications and helpful links

General Publications

• Dale GE, Halabi A, Petersen-Sylla M, Wach A, Zwingelstein C. Pharmacokinetics, Tolerability, and Safety of Murepavadin, a Novel Antipseudomonal Antibiotic, in Subjects with Mild, Moderate, or Severe Renal Function Impairment. Antimicrob Agents Chemother. 2018 Aug 27;62(9):e00490-18. doi: 10.1128/AAC.00490-18. Print 2018 Sep.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: April 8, 2014
• First Submitted That Met QC Criteria: April 8, 2014
• First Posted (Estimate): April 10, 2014

Study Record Updates

• Last Update Posted (Estimate): June 17, 2016
• Last Update Submitted That Met QC Criteria: June 16, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetics; POL7080
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Anti-Infective Agents; Anti-Bacterial Agents; Murepavadin
• Other Study ID Numbers: POL7080-005