The Pharmacokinetic, Safety and Tolerability of Tiotropium in Outpatients With Renal Impairment in Comparison to Healthy Subjects

NCT02172339 | Completed Phase 1

• 1 other identifier: 205.134
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Study to investigate pharmacokinetics of a single i.v. dose of tiotropium (4.8 mcg) in patients with renal impairment in comparison to healthy subjects.

Conditions

Renal Insufficiency

Outcome Measures

Primary Outcomes (4)

• Area under the curve (AUC (0-4h) of plasma levels of tiotropium after dosing)

  pre-dose, 7, 15 , 20, 25, 35, 45 minutes and 1, 2, 4 and 8 hours after drug administration

• Renal clearance of tiotropium (CLren )

  Day 1, 2, 3, 7, 11, 15, 18, 22 and 25 (0-4h, 4-8h), additionally -4 -0 h on day 1

• Terminal half-life of tiotropium

  pre-dose, 7, 15 , 20, 25, 35, 45 minutes and 1, 2, 4 and 8 hours after drug administration

• Urinary excretion (0-4h) of tiotropium, Ae 0-4h

  Day 1, 2, 3, 7, 11, 15, 18, 22 and 25 (0-4h, 4-8h), additionally -4 -0 h on day 1

Secondary Outcomes (8)

• Change from baseline in Pulse Rate (PR)

  baseline, day 1, 2, 3, 7,11, 15,18, 22 and 25

• Change from baseline in Blood pressure (BP)

  baseline, day 1, 2, 3, 7,11, 15,18, 22 and 25

• Number of Participants with Serious and Non-Serious Adverse Events

  up to day 25

• Change from baseline in electrocardiogram (ECG)

  baseline, day 1, 2, 7, 15 and 25

• Maximum measured concentration of the analyte in plasma (Cmax )

  pre-dose, 7, 15 , 20, 25, 35, 45 minutes and 1, 2, 4 and 8 hours after drug administration

Study Arms (1)

Tiotropium

EXPERIMENTAL

group comparison (healthy, renal impairment)

Drug: Tiotropium, solution ampoules

Interventions

Tiotropium, solution ampoules DRUG

Tiotropium

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects:
• Subject with normal renal function ( creatinine clearance of 80% of predicted creatinine clearance in healthy volunteers), as confirmed by normal physical examination including vital signs, ECG and laboratory values
• Calculated creatinine clearance (male);
• = ((140 - age(yr)) x (Wt (kg))) / (72 x predicted serum creatinine (mg/dL))
• Calculated creatinine clearance (female);
• = ((140 - age(yr)) x (Wt(kg))) / (85 x predicted serum creatinine (mg/dL))
• Subject with impaired renal function must be of age related good health and without clinically significant abnormalities as assessed during the physical examination. Mildly impaired renal patients were defined as those with creatinine clearance of 40 - 80% of predicted creatinine clearance; moderately impaired renal patients were defined as those with creatinine clearance of 10 - 40% of predicted creatinine clearance. Laboratory values of subjects with renal impairment could have been outside the normal range if the deviations were due to the underlying renal disease.
• Male or female, age between 40 and 70 years with normal body - weight index (+/- 25%, Broca-index)
• Subjects with normal 12 - lead ECG recording
• Subjects with normal physical examination
• Subjects with normal clinical and laboratory tests (except for indicators of renal impairment)
• Female of child bearing potential must have a negative pregnancy test
• All subjects must have a negative HIV-Ab test and negative Hepatitis B test
• All subjects must have a negative drug screening
• All subjects must sign a written informed consent prior to enrollment

You may not qualify if:

• Subjects with a history of more then moderate alcohol consumption (more than 1 litre of beer per day or the equivalent amount of alcohol in any other alcoholic beverage, approximately 50 g of alcohol per day). 24 hours before dosing and 24 hours post dosing, alcohol was not permitted
• Present or past participation in a drug detoxification program
• Smokers
• Subjects requiring any concomitant medication not compatible with this study
• Subjects with hypotension (systolic blood pressure less than 100 mmHg, diastolic less than 60 mmHg) or hypertension (systolic blood pressure more than 165 mmHg or diastolic more than 100 mmHg) under adequate medication
• Subjects who participated in a clinical trial of any other investigational drug within two months prior to the start of this study
• Pregnant or lactating women or women of child bearing potential not using a medically approved means contraception. (i.e., oral contraceptives, intrauterine devices, diaphragm)
• Subjects who donated blood within three months prior to the start of the study
• Subjects with a history of chronic or recurrent convulsive disorders or ongoing hepatic dysfunction
• Subjects with ongoing acute systemic illness or recovery from acute systemic illness
• Subjects with a history of cancer within the last five years
• Subjects with known hypersensitivity to anticholinergic drugs
• Subjects with known symptomatic prostatic hypertrophy or bladder neck obstruction
• Subjects with known narrow-angle glaucoma

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 24, 2014
• Study Start: April 1, 1998
• Primary Completion: December 1, 1998
• Last Updated: June 24, 2014

Record last verified: 2014-06