Clinical trial NCT03655301: Effect of Copanlisib on Metformin Pharmacokinetics and Pharmacodynamics
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-08-31
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Drug Concentration of Metformin in Plasma After Single Dose Administration (Cmax)
timeFrame: Pre-dose and up to 24 hours after drug administration on Day 1 and Day 8
measure: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours of Metformin After Single Dose Administration (AUC[0-24])
timeFrame: Pre-dose and up to 24 hours after drug administration on Day 1 and Day 8
measure: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity of Metformin After Single Dose Administration (AUC)
timeFrame: Pre-dose and extrapolated up to infinity after drug administration on Day 1 and Day 8
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: From start of study medication until 30 days after end of treatment with study medication.
measure: Number of Participants With Treatment-Emergent Adverse Events by Severity
timeFrame: From start of study medication until 30 days after end of treatment with study medication.
measure: Plasma Lactate Levels
timeFrame: Up to 24 hours after study drug administration on Day 1 and Day 8
measure: Maximum Change From Baseline in Plasma Lactate Levels
timeFrame: From pre-dose up to 24 hours after study drug administration on Day 1 and Day 8
Other outcomes:
Locations:
city: Austin
country: United States
facility: Pharmaceutical Product Development (PPD), LLC
state: Texas
Study officials:
References: