Effect of Copanlisib on Metformin Pharmacokinetics and Pharmacodynamics

NCT03655301 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 19951
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (4)

• Number of Participants With Treatment-Emergent Adverse Events

  From start of study medication until 30 days after end of treatment with study medication.

• Number of Participants With Treatment-Emergent Adverse Events by Severity

  From start of study medication until 30 days after end of treatment with study medication.

• Plasma Lactate Levels

  Up to 24 hours after study drug administration on Day 1 and Day 8

• Maximum Change From Baseline in Plasma Lactate Levels

  From pre-dose up to 24 hours after study drug administration on Day 1 and Day 8

Study Arms (1)

Copanlisib (Aliqopa, BAY80-6946)

EXPERIMENTAL

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); Drug: Metformin

Interventions

Copanlisib (Aliqopa, BAY80-6946) DRUG

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.

Copanlisib (Aliqopa, BAY80-6946)

Metformin DRUG

Single dose of 1000 mg is administered orally.

Copanlisib (Aliqopa, BAY80-6946)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Pharmaceutical Product Development (PPD), LLC

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

copanlisib; Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: August 31, 2018
• Study Start: September 11, 2018
• Primary Completion: November 12, 2018
• Study Completion: February 12, 2019
• Last Updated: January 28, 2020
• Results First Posted: December 23, 2019

Record last verified: 2020-01

Locations

US (1)