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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pharmaceutical Product Development (PPD), LLC | Austin | Texas | 78744 | United States |
A total of 50 participants signed the informed consent form, of them 37 participants were screen failures. The remaining 13 participants received the study treatment.
The study was conducted at one study center in the US, between 11-Sep-2018 (first participant first visit) and 12-Nov-2018 (last participant last visit).
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| ID | Title | Description |
|---|---|---|
| FG000 | Copanlisib (Aliqopa, BAY80-6946) + Metformin | Participants received 2 oral doses of metformin, 1 dose (1000 milligram [mg]) on Day 1 and 1 dose (1000 mg) on Day 8, and a single dose of copanlisib (60 mg, 1 h infusion) on Day 8. A wash-out period of 7 days was maintained between the 2 doses of metformin. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Safey Analysis Set (SAF): included all participants who received at least one dose of the study medication
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| ID | Title | Description |
|---|---|---|
| BG000 | Copanlisib (Aliqopa, BAY80-6946) + Metformin | Participants received 2 oral doses of metformin, 1 dose (1000 milligram [mg]) on Day 1 and 1 dose (1000 mg) on Day 8, and a single dose of copanlisib (60 mg, 1 h infusion) on Day 8. A wash-out period of 7 days was maintained between the 2 doses of metformin. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | SAF |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Pharmacokinetic Analysis Set (PKS): included all participants with a valid PK profile for metformin. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram per liter (mcg/L) | Pre-dose and up to 24 hours after drug administration on Day 1 and Day 8 |
|
From start of study medication until 30 days after end of treatment with study medication, up to 38 days.
The study has only 1 arm with all subjects having received 2 doses on D1 (metformin alone) and D8 (metformin+ copanlisib).The study is not designed to compare the safety following 2 doses.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Copanlisib (Aliqopa, BAY80-6946) + Metformin | Participants received 2 oral doses of metformin, 1 dose (1000 milligram [mg]) on Day 1 and 1 dose (1000 mg) on Day 8, and a single dose of copanlisib (60 mg, 1 h infusion) on Day 8. A wash-out period of 7 days was maintained between the 2 doses of metformin. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear pain | Ear and labyrinth disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Therapeutic Area Head | Bayer | (+) 1-888-8422937 | clinical-trials-contact@bayer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 15, 2018 | Nov 5, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 14, 2018 | Nov 5, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000589253 | copanlisib |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Metformin | Drug | Single dose of 1000 mg is administered orally. |
|
| 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 | 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. |
| 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 |
| 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 |
| Standard Deviation |
| Years |
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| Sex: Female, Male | SAF | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | SAF | Count of Participants | Participants |
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| Race (NIH/OMB) | SAF | Count of Participants | Participants |
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| 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. | Pharmacokinetic Analysis Set (PKS): included all participants with a valid PK profile for metformin. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram*hour per liter (mcg*h/L) | Pre-dose and up to 24 hours after drug administration on Day 1 and Day 8 |
|
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| 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. | Pharmacokinetic Analysis Set (PKS) with valid data for this evaluation. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram*hour per liter (mcg*h/L) | Pre-dose and extrapolated up to infinity after drug administration on Day 1 and Day 8 |
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| 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. | Safety Analysis Set (SAF): included all participants who received at least one dose of the study medication. | Posted | Number | Participants | From start of study medication until 30 days after end of treatment with study medication. |
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|
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| 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. | Safety Analysis Set (SAF): included all participants who received at least one dose of the study medication. | Posted | Count of Participants | Participants | From start of study medication until 30 days after end of treatment with study medication. |
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| 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). | Safety Analysis Set (SAF): included all participants who received at least one dose of the study medication. | Posted | Mean | Full Range | mmol/L | Up to 24 hours after study drug administration on Day 1 and Day 8 |
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| 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. | Safety Analysis Set (SAF): included all participants who received at least one dose of the study medication. | Posted | Mean | Full Range | mmol/L | From pre-dose up to 24 hours after study drug administration on Day 1 and Day 8 |
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| 0 |
| 13 |
| 0 |
| 13 |
| 11 |
| 13 |
| Abdominal distension | Gastrointestinal disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (21.1) | Non-systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (21.1) | Non-systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Paranasal sinus discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Non-systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA (21.1) | Non-systematic Assessment |
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