Clinical trial NCT02110459: Pharmacokinetics and Safety of POL7080 in Patients With Renal Impairment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: POL7080
Pharmacokinetics
Lead sponsor: Polyphor Ltd.
Sponsor class: INDUSTRY
First posted: 2014-04-10
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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

Primary outcomes:
measure: To measure the plasma concentrations of POL7080
timeFrame: 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 outcomes:
measure: Adverse events
timeFrame: Daily assessment up to 7 days from informed consent
measure: Laboratory abnormalities
timeFrame: Screening, Day -1, Day 2, Day 3, and Day 7
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: CRS Clinical Research Services Kiel GmbH
Study officials:
affiliation: CRS Clinical Research Services Kiel GmbH
name: Atef Halabi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.