DDI (Effect of Metformin and Furosemide on Rosuvastatin PK)

Study Overview
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Brief Summary
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The primary objective of this trial is to investigate the relative bioavailability of rosuvastatin when given alone (Reference treatment, R) compared to when given together with one of the three different doses of metformin (10 mg, Test treatment 1 (T1); 50 mg (T2); 500 mg (T3)) or one of the two doses of furosemide (1 mg (T4); 5 mg (T5)).

Official Title
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The Effect of Different Doses of Metformin or Furosemide on Rosuvastatin Pharmacokinetics Following Oral Administration in Healthy Male Subjects (an Open-label, Randomised, Single-dose, Six-way Crossover Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Rosuvastatin
* Drug: Metformin HCl
* Drug: Furosemide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male subjects according to the investigators assessment, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests Age of 18 to 55 years (incl.) BMI of 18.5 to 29.9 kg/m2 (incl.) Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation Exclusion criteria: Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Any evidence of a concomitant disease judged as clinically relevant by the investigator Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair) Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders History of relevant orthostatic hypotension, fainting spells, or blackouts Chronic or relevant acute infections History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day) Inability to refrain from smoking on specified trial days Alcohol abuse (consumption of more than 30 g per day) Drug abuse or positive drug screening Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial Inability to comply with dietary regimen of trial site Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study In addition, the following trial-specific exclusion criteria apply: Myopathy Hereditary galactose or fructose intolerance, lactase deficiency, or glucose-galactose malabsorption Allergy or hypersensitivity against sulfonamides

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R (Reference) Rosuvastatin<br>1film-coated tablet as single dose, fasted | Drug: Rosuvastatin<br> <br> |
| Experimental: T1 (Test 1) Rosuvastatin + Metformin HCl<br>Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Metformin HCl (10 mg) as single dose, fasted | Drug: Rosuvastatin<br> <br> Drug: Metformin HCl<br> <br> |
| Experimental: T2 (Test 2) Rosuvastatin + Metformin HCl<br>Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Metformin HCl (50 mg) as single dose, fasted | Drug: Rosuvastatin<br> <br> Drug: Metformin HCl<br> <br> |
| Experimental: T3 (Test 3) Rosuvastatin + Metformin HCl<br>Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Metformin HCl (500 mg) as single dose, fasted | Drug: Rosuvastatin<br> <br> Drug: Metformin HCl<br> <br> |
| Experimental: T4 (Test 4) Rosuvastatin + Furosemide<br>Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Furosemide: (1 mg) as single dose, fasted | Drug: Rosuvastatin<br> <br> Drug: Furosemide<br> <br> |
| Experimental: T5 (Test 5) Rosuvastatin + Furosemide<br>Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Furosemide: (5 mg) as single dose, fasted | Drug: Rosuvastatin<br> <br> Drug: Furosemide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve of Rosuvastatin From 0 to the Last Quantifiable Data Point (AUC0-tz) | This outcome measure presents the area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). | Blood sampling within 3 hours (h) prior to the study drug administration, at the time of administration (0:00) and 30 minutes, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11h, 12h, 24h, 34h, and 48h thereafter. | 
| Maximum Concentration of Rosuvastatin (Cmax) | This outcome measure presents the maximum measured concentration of rosuvastatin in plasma (Cmax). | Blood sampling within 3 hours (h) prior to the study drug administration, at the time of administration (0:00) and 30 minutes, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11h, 12h, 24h, 34h, and 48h thereafter. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve of Rosuvastatin From 0 Extrapolated to Infinity (AUC0-∞) | This outcome measure presents area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). | Blood sampling within 3 hours (h) prior to the study drug administration, at the time of administration (0:00) and 30 minutes, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11h, 12h, 24h, 34h, and 48h thereafter. |