Effect of Copanlisib on Metformin Pharmacokinetics and Pharmacodynamics

Healthy Volunteers Clinical Trial

Official title:

An Open-label, Non-randomized, Phase I Study to Evaluate the Effect of Copanlisib (a Single Intravenous Dose of 60 mg) on the Pharmacokinetics (PK) and Pharmacodynamics (PD) of Metformin (MATE2-K Substrate) in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03655301
• Other study ID #: 19951
• Status: Completed
• Phase: Phase 1
• Start date: September 11, 2018
• Est. completion date: February 12, 2019

Study information

• Verified date: January 2020
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn about a drug-drug interaction. When two medications are taken together at the same time, one medication may change the activity of the other medication in the body - this is called a drug-drug interaction. This study is looking at the effect the Bayer study drug, copanlisib, has on metformin, a commonly used medication to treat diabetes. During the study, blood and urine samples will be collected and analyzed to learn about pharmacokinetics (how copanlisib changes metformin levels in the body) and pharmacodynamics (the effect metformin has on the body when taken together with copanlisib) when someone takes both copanlisib and metformin together.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: February 12, 2019
• Est. primary completion date: November 12, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Healthy male or female subjects - as determined by the investigator or medically qualified designee based on medical evaluations, including medical history, physical examination, laboratory tests and cardiac monitoring

• Aged 18 to 45 years at the first screening visit

• Body Mass Index (BMI) of 18.0 - 34 kg / m*2 , with body weight = 50 kg

• Creatinine clearance = 90 mL/min using the Modification of Diet in Renal Disease

• Adequate end organ and bone marrow function

Exclusion Criteria:

• Existing relevant diseases of vital organs (e.g. liver diseases, heart diseases), central nervous system (for example seizures) or other organs (e.g. diabetes mellitus)

• Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal

• Relevant respiratory insufficiency / disorder

• Administration of strong CYP3A4 inhibitors or inducers within 2 weeks prior to dosing

• Known history of hypersensitivity (or known allergic reaction) to copanlisib, metformin, related compounds, or any components of the formulation

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Copanlisib (Aliqopa, BAY80-6946)
The copanlisib dose for this study is the standard dose recently approved and also used in Phase 1, 2 and 3 studies across the copanlisib development program: 60 mg i.v. infusion administered intermittently on Days 1, 8 and 15 of a 28-day cycle. In this study subjects will receive a single i.v. dose of 60 mg copanlisib on day 8.
• Metformin
Single dose of 1000 mg is administered orally.

Locations

Country	Name	City	State
United States	Pharmaceutical Product Development (PPD), LLC	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Drug Concentration of Metformin in Plasma After Single Dose Administration (Cmax)	Maximum observed drug concentration of metformin in plasma after single dose administration without copanlisib (Day 1) and in combination with copanlisib (Day 8) were measured.	Pre-dose and up to 24 hours after drug administration on Day 1 and Day 8
Primary	Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours of Metformin After Single Dose Administration (AUC[0-24])	Area under the concentration versus time curve from zero to 24 hours of metformin after single dose administration without copanlisib (Day 1) and in combination with copanlisib (Day 8) were measured.	Pre-dose and up to 24 hours after drug administration on Day 1 and Day 8
Primary	Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity of Metformin After Single Dose Administration (AUC)	Area under the concentration verus time curve from zero to infinity of metformin after single dose without copanlisib (Day 1) and in combination with copanlisib (Day 8) were measured.	Pre-dose and extrapolated up to infinity after drug administration on Day 1 and Day 8
Secondary	Number of Participants With Treatment-Emergent Adverse Events	An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events (TEAEs) were defined as adverse events that started or worsened after the start of study drug administration up to 30 days after last administration of the study medication.	From start of study medication until 30 days after end of treatment with study medication.
Secondary	Number of Participants With Treatment-Emergent Adverse Events by Severity	An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse events (TEAEs) were defined as adverse events that started or worsened after the start of study drug administration up to 30 days after last administration of the study medication. TEAEs per severity were reported.	From start of study medication until 30 days after end of treatment with study medication.
Secondary	Plasma Lactate Levels	Lactate levels were analyzed in plasma samples collected during metformin alone or in combination with copanlisib. Plasma lactate levels were summarized by treatment conditions (Day 1 and Day 8).	Up to 24 hours after study drug administration on Day 1 and Day 8
Secondary	Maximum Change From Baseline in Plasma Lactate Levels	Lactate levels were analyzed in plasma samples collected during metformin alone or in combination with copanlisib. Maximum change from baseline on Day 1 and Day 8 was summarized.	From pre-dose up to 24 hours after study drug administration on Day 1 and Day 8