Pharmacokinetic Interaction Between Trospium With an Inhibitor of OCT1 and of P-gp in Subjects Genotyped for OCT1

NCT03011463 | Completed Phase 1

• 1 other identifier: P334
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is:

• to determine absolute bioavailability, input rates, distribution volume, renal and intestinal excretion of trospium in subjects with wild-type of SLC22A1 rs72552763 and rs12208357 and in subjects with homozygous variant alleles of SLC22A1 rs72552763 or rs12208357
• to determine absolute bioavailability, input rates, distribution volume and renal and intestinal excretion of trospium in subjects with wild-type alleles of SLC22A1 rs72552763 and rs12208357 after co-medication of 300 mg of the OCT1- inhibitor ranitidine
• to determine absolute bioavailability, input rates, distribution volume and renal and intestinal excretion of trospium in subjects with wild-type alleles of SLC22A1 rs72552763 and rs12208357 after co-medication of 500 mg of the P-glycoprotein- inhibitor clarithromycin
• to determine absolute bioavailability, input rates, distribution volume and renal and intestinal excretion of trospium in subjects with homozygous variant alleles of SLC22A1 rs72552763 or rs12208357 after co-medication of 500 mg of the P-glycoprotein- inhibitor clarithromycin.

Conditions

Pharmacokinetics; Inhibition Enzyme; Drug Interaction Potentiation

Outcome Measures

Primary Outcomes (1)

• absolute bioavailability

  ratio oral over intravenous area under the concentration time curve normalized by given dose

  up to 36 h after drug administration

Secondary Outcomes (4)

• input rates

  up to 36 h after drug administration

• volume of distribution

  up to 36 h after drug administration

• renal excretion

  up to 36 h after drug administration

• intestinal excretion

  up to 36 h after drug administration

Study Arms (6)

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

Drug: oral administration of 30 mg trospium chloride; Drug: oral administration of 300 mg ranitidine

trospium oral with clarithromycin

ACTIVE COMPARATOR

Oral administration of 30 mg trospium chloride together with 500 mg clarithromycin with 240 ml tap water

Drug: oral administration of 30 mg trospium chloride; Drug: oral administration of 500 mg clarithromycin

Interventions

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; trospium intravenous with clarithromycin; trospium intravenous with ranitidine

oral administration of 30 mg trospium chloride DRUG

oral administration of 30 mg trospium chloride with 240 ml tap water

trospium oral; trospium oral with clarithromycin; trospium oral with ranitidine

oral administration of 300 mg ranitidine DRUG

oral administration of 300 mg ranitidine with 240 ml tap water

trospium intravenous with ranitidine; trospium oral with ranitidine

oral administration of 500 mg clarithromycin DRUG

oral administration of 500 mg clarithromycin with 240 ml tap water

trospium intravenous with clarithromycin; trospium oral with clarithromycin

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr. R. Pfleger Chemische Fabrik GmbH: lead

MeSH Terms

Interventions

trospium chloride; Ranitidine; Clarithromycin

Intervention Hierarchy (Ancestors)

Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: top doctor, clinical trial center

Study Record Dates

• First Submitted: January 2, 2017
• First Posted: January 5, 2017
• Study Start: November 1, 2016
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: April 10, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share