Study of Copanlisib in Hepatic or Renal Impairment

ID: NCT03172884
Status: Recruiting
Phase: Phase 1
Start Date: June 14, 2017
First Submitted: May 30, 2017
Last Updated: February 23, 2018
Results: N/A
Organization: Bayer
Sponsors & Collaborators: Bayer
Location: Germany, Romania
Conditions: Hepatic Insufficiency
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Study Description

Brief Summary

To evaluate the pharmacokinetics and safety of copanlisib in subjects with impaired hepatic or renal function in comparison to healthy subjects

Detailed Description

Condition or disease Intervention/treatment Phase

Hepatic Insufficiency

Drug: Copanlisib BAY80-6946
Other Names
Phase 1

Tracking Information

First Submitted DateMay 30, 2017
Last Update Posted DateFebruary 23, 2018
Actual Start DateJune 14, 2017
Anticipated Completion DateJuly 17, 2019
Actual Primary Completion DateApril 10, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • AUC(0-168) and AUC [Time Frame: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusion]

    AUC and AUC(0-168) of copanlisib in plasma with moderate hepatic (Child Pugh B), severe hepatic (Child Pugh C) or severe renal impairment compared with healthy subjects

  • Cmax [Time Frame: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusion]

    Maximum observed drug concentration (Cmax) of copanlisib

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Frequency of treatment-emergent adverse events (TEAE) [Time Frame: Up to 30 days after study drug]

    All adverse events that occur at or after study drug administration and up to approximately 4 weeks after will be collected

  • Cmax of M-1 metabolite [Time Frame: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusion]

    Maximum observed drug concentration of M-1 metabolite

  • AUC(0-168) of M-1 metabolite [Time Frame: before copanlisib administration as well as 10 min and 1 h (end of infusion), 1.5, 2, 2.5, 3, 5, 8, 24, 48, 72, 96, 120 and 168 h after start of infusion]

    AUC from time 0 to 168h of M-1 metabolite

  • Severity of treatment-emergent adverse events (TEAE) [Time Frame: Up to 30 days after study drug administration]

    All adverse events that occur at or after study drug administration and up to approximately 4 weeks after will be collected

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleStudy of Copanlisib in Hepatic or Renal Impairment
Official TitleAn Open-label Non-randomized, Phase 1 Single Dose Study to Evaluate the Pharmacokinetics and Safety of Copanlisib in Subjects With Impaired Hepatic or Renal Function in Comparison to Healthy Subjects
Brief Summary

To evaluate the pharmacokinetics and safety of copanlisib in subjects with impaired hepatic or renal function in comparison to healthy subjects

Detailed Description

Study TypeInterventional
Study PhasePhase 1
Estimated Enrollment
44
Allocation
Non-Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Other
Conditions
Hepatic Insufficiency
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Copanlisib BAY80-6946

12mg single dose, intravenous on Day 0

Other Names
Study Groups/Cohorts
BAY80-6946/Healthy subject
Healthy subjects

BAY80-6946/moderate hepatically impaired patients
Patients with moderate impairment of the liver (Child Pugh B)

BAY80-6946/severe renal impaired patients
Patients with severe impairment of the kidneys

BAY80-6946/severe hepatically impaired patients
Patients with severe impairment of the liver (Child Pugh C)

Study Arms
Experimental BAY80-6946/Healthy subject
Healthy subjects
Drug : Copanlisib BAY80-6946
12mg single dose, intravenous on Day 0

Experimental BAY80-6946/moderate hepatically impaired patients
Patients with moderate impairment of the liver (Child Pugh B)
Drug : Copanlisib BAY80-6946
12mg single dose, intravenous on Day 0

Experimental BAY80-6946/severe hepatically impaired patients
Patients with severe impairment of the liver (Child Pugh C)
Drug : Copanlisib BAY80-6946
12mg single dose, intravenous on Day 0

Experimental BAY80-6946/severe renal impaired patients
Patients with severe impairment of the kidneys
Drug : Copanlisib BAY80-6946
12mg single dose, intravenous on Day 0

Arm Intervention/Treatment
Experimental BAY80-6946/Healthy subject
Healthy subjects
Drug : Copanlisib BAY80-6946
Experimental BAY80-6946/moderate hepatically impaired patients
Patients with moderate impairment of the liver (Child Pugh B)
Drug : Copanlisib BAY80-6946
Experimental BAY80-6946/severe hepatically impaired patients
Patients with severe impairment of the liver (Child Pugh C)
Drug : Copanlisib BAY80-6946
Experimental BAY80-6946/severe renal impaired patients
Patients with severe impairment of the kidneys
Drug : Copanlisib BAY80-6946

Recruitment Information

Recruitment Status:Recruiting
Enrollment44
Completion DateJuly 17, 2019
Eligibility Criteria: Inclusion Criteria:
All subjects - Male and female subjects between 18 and 80 years of age with a body mass index above 18.0 and below 34.0 kg / m² and a body weight of above or equal 50 kg.
Healthy subjects
- Healthy subjects as determined by absence of clinically significant deviation from normal in medical history, physical examination, vital signs, electrocardiograms, and clinical laboratory determinations. eGFR ≥ 90 mL/min/1.73 m² (according to Modification of Diet in Renal Disease [MDRD] formula).
Subjects with moderate hepatic impairment
- Subjects with confirmed liver cirrhosis by at least one of the following criteria: histologically by prior liver biopsy showing cirrhosis, liver imaging (computer tomography, and/or ultrasound and/or magnetic resonance imaging scans, and/or fibroscan), or laparoscopy.
- Child-Pugh Clinical Assessment Score 7 to 9. Subjects with severe renal impairment
- Subjects with severe renal impairment with an estimated glomerular filtration rate 15-29 mL/min/1.73 m² according to MDRD formula.
- Subjects with stable renal disease: no significant change in renal function as evidenced by serum creatinine value within ±25% from the last determination, obtained within at least 3 months before study entry and the absence of the need to start dialysis in the next 3 months.

Exclusion Criteria:
All subjects
- Active coronary artery disease or myocardial infarction within 6 months of study entry. Immuno-compromised subjects including known history/seropositivity of human immunodeficiency virus (HIV).
- Other concurrent severe and/or uncontrolled medical conditions (e.g. current diagnosis of type 1 or type 2 diabetes mellitus and with HbA1c >8.5%) that could cause unacceptable safety risks or compromise compliance with protocol.
- Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder cancer as well as localized prostate cancer.
- Uncontrolled hypertension despite optimal medical management (per investigator's assessment).
- Administration of strong CYP3A4 inhibitors or inducers within 2 weeks prior to dosing and during study conduct. (A list of these medications can be found in Section 16.6 of the protocol. However, this list may not be comprehensive).Subjects with moderate hepatic impairment
- Symptoms or history of encephalopathy
- Failure of any other major organ other than the liver; severe infection, or any clinically significant illness within 4 weeks prior to study drug administration
- Renal failure with an eGFR <35 mL/min/1.73 m² Subjects with severe renal impairment
- Acute renal failure at study entry
- Nephrotic syndrome
- Failure of any other major organ other than the kidney
- Acute hepatorenal syndrome
GenderAll
Age18 Years to 80 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
Contacts
Listed Location Countries
Germany
Romania

Administrative Information

NCT Number:NCT03172884
Other Study ID Numbers
18041
2016-004561-51
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Bayer
Collaborators
Not Available
Investigators
Study Director
Bayer Study Director
Bayer