Pharmacokinetics, Safety and Tolerability of Digoxin With or Without Co-administration of BI 1356 in Healthy Volunteers

NCT02183402 | Completed Phase 1

• 1 other identifier: 1218.29
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to investigate the pharmacokinetics, safety and tolerability of digoxin with and without co-administration of BI 1356. Additionally the steady state pharmacokinetics of BI 1356 when co-administered with digoxin will be determined.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• AUCτ,ss (area under the concentration-time curve in plasma at steady state over a uniform dosing interval τ) for digoxin

  before (-0:30) administration of digoxin, 0:30, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 24:00, 48:00, 72:00, 96:00, 120:00, and 144:00 hours after administration of digoxin

• Cmax,ss (maximum measured concentration in plasma at steady state over a uniform dosing interval τ) for digoxin

  before (-0:30) administration of digoxin, 0:30, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 24:00, 48:00, 72:00, 96:00, 120:00, and 144:00 hours after administration of digoxin

• CLR,ss (renal clearance at steady state) for digoxin

  0-2 h, 2-4 h, 4-8 h, 8-12 h, 12-24 h, 24-48 h, 48-72 h, 72-96 h, 96-120 h, and 120-144 h after drug last administration on day 11

Secondary Outcomes (23)

• AUC0-∞,ss (area under the concentration-time curve of the analyte in plasma at steady state over the time interval from 0 extrapolated to infinity) for digoxin

  before (-0:30) administration of digoxin, 0:30, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 24:00, 48:00, 72:00, 96:00, 120:00, and 144:00 hours after administration of digoxin

• AUC0-tz,ss (area under the concentration-time curve of the analyte in plasma at steady state over the time interval from 0 to the last quantifiable drug plasma concentration ) for digoxin

  before (-0:30) administration of digoxin, 0:30, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 24:00, 48:00, 72:00, 96:00, 120:00, and 144:00 hours after administration of digoxin

• AUCt1-t2,ss (area under the concentration-time curve of the analyte in plasma at steady state over the time interval t1 to t2) for digoxin

  before (-0:30) administration of digoxin, 0:30, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 24:00, 48:00, 72:00, 96:00, 120:00, and 144:00 hours after administration of digoxin

• tmax,ss (time from (last) dosing to the maximum measured concentration of the analyte in plasma at steady state) for digoxin

  before (-0:30) administration of digoxin, 0:30, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 24:00, 48:00, 72:00, 96:00, 120:00, and 144:00 hours after administration of digoxin

• λz,ss (terminal rate constant of the analyte in plasma at steady state) for digoxin

  before (-0:30) administration of digoxin, 0:30, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 24:00, 48:00, 72:00, 96:00, 120:00, and 144:00 hours after administration of digoxin

Study Arms (2)

Digoxin with BI 1356

EXPERIMENTAL

Drug: Digoxin; Drug: BI 1356

Digoxin

ACTIVE COMPARATOR

Drug: Digoxin

Interventions

Digoxin DRUG

Digoxin; Digoxin with BI 1356

BI 1356 DRUG

Digoxin with BI 1356

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy females and males according to the following criteria: based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
• Age ≥ 18 and age ≤ 50 years
• BMI ≥ 18.5 and BMI ≤ 29.9 kg/m2 (Body Mass Index)
• Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation

You may not qualify if:

• Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
• Any evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections (e.g., HIV)
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs with a long half-life (\> 24 hours) within at least one month or less than five half-lives of the respective drug prior to administration or during the trial
• Use of drugs which could reasonably influence the results of the trial or that prolonged the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
• Participation in another trial 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 trial days
• Alcohol abuse (more than 60 g/day) or inability to stop alcoholic beverages for 24 hours prior to dosing and up to the last sampling time point
• Drug abuse

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

Digoxin; Linagliptin

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Study Design

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

Study Record Dates

• First Submitted: July 4, 2014
• First Posted: July 8, 2014
• Study Start: June 1, 2008
• Primary Completion: September 1, 2008
• Last Updated: July 8, 2014

Record last verified: 2014-07