Clinical trial NCT03172884: Study of Copanlisib in Hepatic or Renal Impairment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Insufficiency, Renal Insufficiency
Keywords: Renal Impairment
Pharmacokinetics
Hepatic impairment
Envisaged indication: Treatment of cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2017-06-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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


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 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

Primary outcomes:
measure: Maximum Observed Concentration (Cmax) of Copanlisib in Plasma.
timeFrame: 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
measure: Area Under the Concentration vs. Time Curve From Zero to Infinity (AUC) of Copanlisib in Plasma.
timeFrame: 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
measure: Area Under the Concentration-time Curve of Copanlisib in Plasma Over the Time Interval From 0 to 168 h.
timeFrame: 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 outcomes:
measure: Maximum Observed Concentration (Cmax) of Metabolite M-1.
timeFrame: 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
measure: Area Under the Concentration-time Curve of Metabolite M-1 in Plasma Over the Time Interval From 0 to 168 h.
timeFrame: 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
measure: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 30 days after end of treatment with study drug
measure: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) in Different Severity.
timeFrame: Up to 30 days after end of treatment with study drug
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: CRS Clinical-Research-Services Kiel GmbH
state: Schleswig-Holstein
city: Bucuresti
country: Romania
facility: Institutul National de Boli Infectioase Prof.Dr.Matei Bals
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: