Study of Copanlisib in Hepatic or Renal Impairment
Condition: Hepatic Insufficiency, Renal Insufficiency
MeSH terms: Hepatic Insufficiency; Liver Failure; Renal Insufficiency
Intervention: Copanlisib (ALIQOPA, BAY80-6946)
Intervention description: 12mg single dose, intravenous on Day 0
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Renal Impairment; Pharmacokinetics; Hepatic impairment; Envisaged indication: Treatment of cancer

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