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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Ranitidine + Tiotropium; Drug: Cimetidine + Tiotropium; Drug: Tiotropium

• Registration Number: NCT02172417
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2000-07
• Primary Completion: 2000-11
• Status Verified: 2014-06
• Study First Submitted: 2014-06-20
• Study First Submitted QC: 2014-06-20
• Last Update Submitted: 2014-06-20
• Study First Posted: 2014-06-24
• Last Update Posted: 2014-06-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ranitidine + Tiotropium followed by Tiotropium	Ranitidine + Tiotropium	-
Ranitidine + Tiotropium followed by Tiotropium	Tiotropium	-
Cimetidine + Tiotropium followed by Tiotropium	Cimetidine + Tiotropium	-
Cimetidine + Tiotropium followed by Tiotropium	Tiotropium	-

Primary Outcome Measures

Name	Time	Method
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
Urinary excretion 0-4h after dosing (Ae0-4h)	0 - 4 hours after i.v. treatment
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

Secondary Outcome Measures

Name	Time	Method
Changes from baseline in physical examination	Baseline, 4 - 8 days after last i.v. treatment
Changes in 12-lead electrocardiogram (ECG)	up to 24 h after i.v. 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
AUC 0-8h of plasma levels of tiotropium after dosing	0-8 hours after treatment
Changes in Blood Pressure and Pulse Rate	up to 4 - 8 days after last i.v. treatment