Study of Copanlisib in Hepatic or Renal Impairment

An 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

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

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency, Renal Insufficiency
• Intervention / Treatment: Drug: Copanlisib (ALIQOPA, BAY80-6946)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • CRS Clinical-Research-Services Kiel GmbH
• Romania
  • Bucuresti, Romania, 021105
    • Institutul National de Boli Infectioase Prof.Dr.Matei Bals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 or severe 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 (moderate) or Score 10 to 15 (severe).

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 or severe hepatic impairment

• Symptoms or history of encephalopathy (Grade III or worse)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY80-6946/Healthy subject; Healthy subjects	Drug: Copanlisib (ALIQOPA, BAY80-6946); 12mg single dose, intravenous on Day 0
Experimental: BAY80-6946/moderate hepatically impaired patients; Patients with Child-Pugh B (score 7-9) at the screening visit	Drug: Copanlisib (ALIQOPA, BAY80-6946); 12mg single dose, intravenous on Day 0
Experimental: BAY80-6946/severe renal impaired patients; Patients with eGFR 15-29 mL/min/1.73 m^2 at the screening visit based on the Modification of Diet in Renal Disease (MDRD) equation	Drug: Copanlisib (ALIQOPA, BAY80-6946); 12mg single dose, intravenous on Day 0
Experimental: BAY80-6946/severe hepatically impaired patients; Patients with Child-Pugh C (score 10-15) at the screening visit	Drug: Copanlisib (ALIQOPA, BAY80-6946); 12mg single dose, intravenous on Day 0

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of Copanlisib in Plasma.	Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.	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
Area Under the Concentration vs. Time Curve From Zero to Infinity (AUC) of Copanlisib in Plasma.	AUC refers to area under the concentration vs time curve from 0 to infinity which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.	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
Area Under the Concentration-time Curve of Copanlisib in Plasma Over the Time Interval From 0 to 168 h.	AUC(0-168) refers to AUC from time 0 to 168 hr which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of Metabolite M-1.	The morpholinone derivative M-1 is a minor copanlisib metabolite in plasma. The PK of metabolite M-1 is routinely analyzed in addition to the PK of the parent compound, although M-1 is not considered to be a major metabolite. Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.	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
Area Under the Concentration-time Curve of Metabolite M-1 in Plasma Over the Time Interval From 0 to 168 h.	The morpholinone derivative M-1 is a minor copanlisib metabolite in plasma. The PK of metabolite M-1 is routinely analyzed in addition to the PK of the parent compound, although M-1 is not considered to be a major metabolite. AUC from time 0 to 168h which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.	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
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)	Adverse events are considered to be treatment-emergent if they have started or worsened after first application of study medication up to 30 days after end of treatment with study medication.	Up to 30 days after end of treatment with study drug
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) in Different Severity.	Adverse events are considered to be treatment-emergent if they have started or worsened after first application of study medication up to 30 days after end of treatment with study medication.	Up to 30 days after end of treatment with study drug

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• Click here to find results for studies related to Bayer Healthcare products.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2017
• Primary Completion (Actual): March 13, 2020
• Study Completion (Actual): May 15, 2020

Study Registration Dates

• First Submitted: May 30, 2017
• First Submitted That Met QC Criteria: May 31, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Renal Impairment; Hepatic impairment; Envisaged indication: Treatment of cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Kidney Diseases; Urologic Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Renal Insufficiency
• Other Study ID Numbers: 18041; 2016-004561-51 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, time point and process of data access. As such, Bayer commits to sharing upon request from qualified researcher's patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

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