Tiotropium in Combination With Concomitant Cimetidine or Ranitidine in Healthy Male and Female Subjects

The Effect of Concomitant Cimetidine p.o. 400 mg t.i.d. and p.o. Ranitidine 300 mg Once Daily on Single Dose Pharmacokinetics of Tiotropium (14.4 µg) Given Intravenously Over 15 Minutes in Healthy Male and Female Subjects of 50-65 Years (Randomized, Open Label, Two Independent Two-fold Crossover)

Study to investigate the effect of an inhibition of the renal cationic drug transporter on single dose pharmacokinetics of intravenous tiotropium in subjects in an age close to typical Chronic Obstructive Pulmonary Disease (COPD) population

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tiotropium; Drug: Cimetidine + Tiotropium; Drug: Ranitidine + Tiotropium

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy males or females
• Age range from 50 to 65 years
• Within 20% of their normal weight (Broca index)

Exclusion Criteria:

• Any finding of the medical examination (including blood pressure, puls rate and ECG) deviating from normal and of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Diseases of the central nervous system (such as epilepsy) or with psychiatric disorders or neurological disorders
• History of orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Intake of a drug with a long half-life (≥ 24 hours) within ten half-lives of the respective drug before enrolment in the study or during the study (exclusion: ovarian hormone substitution)
• Use of any drugs which might influence the results of the trial within four weeks prior to administration or during the trial, among these all non-selective β-blockers, cromolyn sodium, nedocromil sodium, oral β-adrenergics or long-acting β-adrenergics such as salmeterol and formoterol, and anticholinergic drugs including ATROVENT® (ipratropium) by oral inhalation or ATROVENT® Nasal Spray
• Participation in another study with an investigational drug within two months prior to administration or during the trial
• Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day)
• Inability to refrain from smoking on study days
• Alcohol abuse (> 40 g/day)
• Drug abuse
• Blood donation (≥ 100 ml) within four weeks prior to administration or during the trial
• Excessive physical activities within 5 days prior to administration or during the trial
• Any laboratory value outside the reference range of clinical relevance
• Subjects with known hypersensitivity to anticholinergic drugs
• Subjects with known symptomatic prostatic hypertrophy or disturbed micturition
• Subjects with known narrow-angle glaucoma

In addition for female subjects (if appropriate):

• Pregnancy
• Positive pregnancy test
• No adequate contraception e.g. oral contraceptives, sterilization, intra uterine pessary (IUP)
• Inability to maintain this adequate contraception during the whole study period
• Lactation period

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cimetidine + Tiotropium followed by Tiotropium	Drug: Tiotropium; Drug: Cimetidine + Tiotropium
Experimental: Ranitidine + Tiotropium followed by Tiotropium	Drug: Tiotropium; Drug: Ranitidine + Tiotropium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax of plasma levels of tiotropium after dosing	up to 8 hours after i.v. treatment
Area under the curve (AUC) 0-4h of the plasma levels of tiotropium after dosing	0 - 4 hours after i.v. treatment
Urinary excretion 0-4h after dosing (Ae0-4h)	0 - 4 hours after i.v. treatment
Renal clearance of tiotropium (CLR)	pre-dose, 0-4 h, 4-8 h, 8-12 h, 12-24 , 24-28 h, 38-72 h and 72-96 h after i.v. treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC 0-8h of plasma levels of tiotropium after dosing	0-8 hours after treatment
Urinary excretion 0-96h after dosing (Ae0-96h)	0-96 hours after treatment
Occurrence of Adverse Events	up to 4 - 8 days after last i.v. treatment
Changes from baseline in Laboratory Tests	Baseline, 4 - 8 days after last i.v. treatment
Changes in 12-lead electrocardiogram (ECG)	up to 24 h after i.v. treatment
Changes in Blood Pressure and Pulse Rate	up to 4 - 8 days after last i.v. treatment
Changes from baseline in physical examination	Baseline, 4 - 8 days after last i.v. treatment

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2000
• Primary Completion (Actual): November 1, 2000

Study Registration Dates

• First Submitted: June 20, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Estimate): June 24, 2014
• Last Update Submitted That Met QC Criteria: June 20, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Gastrointestinal Agents; Cytochrome P-450 Enzyme Inhibitors; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Cytochrome P-450 CYP1A2 Inhibitors; Histamine H2 Antagonists; Tiotropium Bromide; Ranitidine; Ranitidine bismuth citrate; Cimetidine
• Other Study ID Numbers: 205.222