Pharmacokinetic Interaction Between Trospium With an Inhi... | NCT03011463

NCT03011463

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
trospium intravenous	Active Comparator	Intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and 240 ml tap water p.o.	Drug: intravenous infusion of 2 mg trospium chloride
trospium oral	Active Comparator	Oral administration of 30 mg trospium chloride with 240 ml tap water	Drug: oral administration of 30 mg trospium chloride
trospium intravenous with ranitidine	Active Comparator	Intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and oral administration of 300 mg ranitidine with 240 ml tap water	Drug: intravenous infusion of 2 mg trospium chloride Drug: oral administration of 300 mg ranitidine
trospium intravenous with clarithromycin	Active Comparator	Intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and oral administration of 500 mg clarithromycin with 240 ml tap water	Drug: intravenous infusion of 2 mg trospium chloride Drug: oral administration of 500 mg clarithromycin
trospium oral with ranitidine	Active Comparator	Oral administration of 30 mg trospium chloride together with 300 mg ranitidine with 240 ml tap water

Interventions

Name	Type	Description	Arm Group Labels	Other Names
intravenous infusion of 2 mg trospium chloride	Drug	intravenous infusion of 2 mg trospium chloride in 20 ml saline within 60 min and 240 ml tap water p.o	trospium intravenous

Measure	Description	Time Frame
absolute bioavailability	ratio oral over intravenous area under the concentration time curve normalized by given dose	up to 36 h after drug administration

Measure	Description	Time Frame
input rates		up to 36 h after drug administration
volume of distribution		up to 36 h after drug administration
renal excretion

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

ethnic origin: Caucasian
genotypes of OCT1: wild-type and homozygous variant alleles of SLC22A1 rs72552763 or rs12208357.
body mass index: ≥ 18.5 kg/m² and ≤ 30 kg/m²
good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state (blood pressure between 110/70 and 140/90 for males and between 100/60 and 140/90 for females, heart rate over 50 bpm up to 90 bpm, laboratory values within the reference ranges as given actually by the laboratory and stored in the TMF)
written informed consent

Exclusion Criteria:

hepatic and renal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the study medication (e.g. hepatic or renal dysfunction, obstruction of the urine flow with urinary retention by subvesical obstruction like benign prostatic hyperplasia, infections or tumors of the urinary tract)
organic causes for polydipsia and pollakiuria
existing cardiac or hematological diseases and/or pathological findings, which might interfere with the drug's safety, tolerability and/or pharmacokinetics (e.g. tachycardia, tachyarrhythmia, bradycardia, heart failure, coronary heart disease, disturbance of the stimulus conduction)
pneumonia
pharyngitis
acute phorphyria
hyperthyroidism
galactose-intolerance, lactase deficiency or glucose-galactose malabsorption
electrolyte disturbance
gastrointestinal diseases and/or pathological findings (e.g. hiatus hernia with gastroesophageal reflux, stenosis, ulcera, severe chronic inflammatory bowel disease like ulcerative colitis or Crohn's disease, toxic megacolon), which might interfere with pharmacokinetics and pharmacodynamics of the study medication)
autonomic neuropathy
myasthenia gravis
narrow-angle glaucoma
drug or alcohol dependence
positive drug or alcohol screening
smokers of 10 or more cigarettes per day
positive results in HIV, HBV and HCV screenings
subjects who are on a diet which could affect the pharmacokinetics of the drugs (e. g. vegans, vegetarians)
heavy tea or coffee drinkers (more than 1L per day)
lactation, pregnancy test positive or not performed or women of child-bearing age without safe contraception as stated in the Note for Guidance on Non-clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceutical (CPMP/ICH/286/95 modifications: implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner and barrier-methods only in combination with one of the aforementioned)
subjects suspected or known not to follow instructions of the clinical investigators
subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study
subjects liable to orthostatic dysregulation, fainting, or blackouts
participation in a clinical trial during the last 3 months prior to the start of the study
less than 14 days after last acute disease
less than 3 months after last blood donation
any medication within 4 weeks prior to the intended first administration of the study medication which might influence functions of the gastrointestinal tract (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists, proton pump inhibitors, anticholinergics)
any other medication within two weeks prior to the first administration of the study medication, but at least 10-time the half-live of the respective drug (except oral contraceptives)
intake of grapefruit or orange containing food or beverages within 14 days prior to administration of the study medication
intake of poppy seed containing food or beverages within 14 days prior to administration of the study medication
known allergic reactions to the active ingredients used, other H2-receptor antagonists, macrolide antibiotics or to constituents of the study medication

ID	Term
C003330	trospium chloride
D011899	Ranitidine
D017291	Clarithromycin

ID	Term
D005663	Furans
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D004917	Erythromycin
D018942	Macrolides
D061065	Polyketides
D007783	Lactones
D009930	Organic Chemicals