Study of Copanlisib in Hepatic or Renal Impairment

NCT03172884 | Completed Phase 1 Results

• 2 other identifiers: 180412016-004561-51
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 2

Brief Summary

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

Conditions

Hepatic Insufficiency, Renal Insufficiency

Keywords

Renal Impairment; Pharmacokinetics; Hepatic impairment; Envisaged indication: Treatment of cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Maximum Observed Concentration (Cmax) of Metabolite M-1.

  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.

  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)

  Up to 30 days after end of treatment with study drug

• Number of Subjects With Treatment-emergent Adverse Events (TEAEs) in Different Severity.

  Up to 30 days after end of treatment with study drug

Study Arms (4)

BAY80-6946/Healthy subject

EXPERIMENTAL

Healthy subjects

Drug: Copanlisib (ALIQOPA, BAY80-6946)

BAY80-6946/moderate hepatically impaired patients

EXPERIMENTAL

Patients with Child-Pugh B (score 7-9) at the screening visit

Drug: Copanlisib (ALIQOPA, BAY80-6946)

BAY80-6946/severe renal impaired patients

EXPERIMENTAL

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)

BAY80-6946/severe hepatically impaired patients

EXPERIMENTAL

Patients with Child-Pugh C (score 10-15) at the screening visit

Drug: Copanlisib (ALIQOPA, BAY80-6946)

Interventions

Copanlisib (ALIQOPA, BAY80-6946) DRUG

12mg single dose, intravenous on Day 0

BAY80-6946/Healthy subject; BAY80-6946/moderate hepatically impaired patients; BAY80-6946/severe hepatically impaired patients; BAY80-6946/severe renal impaired patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (2)

CRS Clinical-Research-Services Kiel GmbH

Kiel, Schleswig-Holstein, 24105, Germany

Location

Institutul National de Boli Infectioase Prof.Dr.Matei Bals

Bucharest, 021105, Romania

Location

Related 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.

MeSH Terms

Conditions

Hepatic Insufficiency; Renal Insufficiency

Interventions

copanlisib

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 1, 2017
• Study Start: June 14, 2017
• Primary Completion: March 13, 2020
• Study Completion: May 15, 2020
• Last Updated: April 28, 2021
• Results First Posted: April 1, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

RO (1); DE (1)