Effect of Copanlisib on Metformin Pharmacokinetics and Pharmacodynamics

• ClinicalTrials.gov Identifier: NCT03655301
• Recruitment Status: Completed
• First Posted: August 31, 2018
• Results First Posted: December 23, 2019
• Last Update Posted: January 28, 2020
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Drug: Copanlisib (Aliqopa, BAY80-6946); Drug: Metformin	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 11, 2018
• Actual Primary Completion Date: November 12, 2018
• Actual Study Completion Date: February 12, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: Copanlisib (Aliqopa, BAY80-6946); All subjects will receive a single dose of metformin 1000 mg on Days 1 and 8 in a fasting state. Subjects will also receive a single i.v. dose of 60 mg copanlisib on Day 8 as part of the combination with metformin.

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.; Drug: Metformin; Single dose of 1000 mg is administered orally.

Outcome Measures

Primary Outcome Measures :

1. Maximum Drug Concentration of Metformin in Plasma After Single Dose Administration (Cmax) [ Time Frame: Pre-dose and up to 24 hours after drug administration on Day 1 and Day 8 ]
   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.
2. Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours of Metformin After Single Dose Administration (AUC[0-24]) [ Time Frame: Pre-dose and up to 24 hours after drug administration on Day 1 and Day 8 ]
   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.
3. Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity of Metformin After Single Dose Administration (AUC) [ Time Frame: Pre-dose and extrapolated up to infinity after drug administration on Day 1 and Day 8 ]
   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.

Secondary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events [ Time Frame: From start of study medication until 30 days after end of treatment with study medication. ]
   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.
2. Number of Participants With Treatment-Emergent Adverse Events by Severity [ Time Frame: From start of study medication until 30 days after end of treatment with study medication. ]
   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.
3. Plasma Lactate Levels [ Time Frame: Up to 24 hours after study drug administration on Day 1 and Day 8 ]
   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).
4. Maximum Change From Baseline in Plasma Lactate Levels [ Time Frame: From pre-dose up to 24 hours after study drug administration on Day 1 and Day 8 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, Texas

Pharmaceutical Product Development (PPD), LLC

Austin, Texas, United States, 78744

Sponsors and Collaborators

Bayer

  Study Documents (Full-Text)

Documents provided by Bayer:

Study Protocol  [PDF] May 15, 2018

Statistical Analysis Plan  [PDF] December 14, 2018

More Information

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT03655301
• Other Study ID Numbers: 19951
• First Posted: August 31, 2018
• Results First Posted: December 23, 2019
• Last Update Posted: January 28, 2020
• Last Verified: January 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Metformin; Hypoglycemic Agents; Physiological Effects of Drugs