Influence of Pantoprazole on the Pharmacokinetics of Fradafiban After Multiple Oral Doses of Lefradafiban Over 5 Days in Healthy Subjects

Influence of 40 mg Pantoprazole Per Day on the Pharmacokinetics of Fradafiban After Multiple Oral Doses of 30 mg Lefradafiban Tid as Acid Free Tablet and Sachet Over 5 Days in Healthy Subjects. A 4-way Crossover Randomized Open Trial

To assess the absorption of 30 mg Lefradafiban in two formulations, each under physiological conditions and with 40 mg Pantoprazole

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Pantoprazole; Drug: Lefradafiban tablet; Drug: Lefradafiban double chamber sachet

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects as determined by results of screening
• Signed written informed consent in accordance with good clinical practice (GCP) and local legislation
• Age ≥ 18 and ≤ 60 years, planned stratification: age < 40 years (4 subjects) and ≥ 40 years (8 subjects)
• Broca ≥ - 20 % and ≤ + 20 %

Exclusion Criteria:

• Use of any drugs which might influence the results of the trial within 10 days prior to administration or during the trial
• Intake of drugs with a long half-life (> 24 hours) within 1 month prior to administration
• Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
• Drug abuse
• Alcohol abuse (> 60 g/day)
• Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days
• Excessive physical activities within 5 days prior to administration or during the trial
• Blood donation within 1 month prior to administration or during the trial
• History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hormonal disorders
• Chronic or relevant acute infections
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders

• History of

  • Allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
  • Any bleeding disorder including prolonged or habitual bleeding
  • Other hematologic disease
  • Cerebral bleeding (e.g. after a car accident
• Recent surgical procedures
• Thrombocytes < 150000/µ
• Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
• Any laboratory value outside the clinically accepted reference range
• Other disease or abnormality of clinical relevance

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lefradafiban tablet with pantoprazole	Drug: Pantoprazole; Drug: Lefradafiban tablet
Active Comparator: Lefradafiban tablet	Drug: Lefradafiban tablet
Experimental: Lefradafiban double chamber sachet with pantoprazole	Drug: Pantoprazole; Drug: Lefradafiban double chamber sachet
Active Comparator: Lefradafiban double chamber sachet	Drug: Lefradafiban double chamber sachet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of the analyte in plasma at steady state, 13th dosing interval (AUCss,13)	Up to 168 hours after first drug administration
Maximum concentration of the analyte in plasma at steady state, 13th dosing interval (Cmax,ss,13)	Up to 168 hours after first drug administration
Pre-dose concentration of the analyte in plasma at steady state, 13th dosing interval (Cpre,ss,13)	Up to 168 hours after first drug administration
Amount of the analyte eliminated unchanged in the urine per dosing interval i expressed as percent of applied dose and corrected for molecular weight differences (Ae% (i=1,...,13))	Up to 168 hours after first drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-dose concentration of the analyte in plasma for the i-th dosing interval (Cpre,i (i=1,4,7,10,11,12))		Up to 90 hours after first drug administration
Plasma concentration of the analyte at 2 hours post-dose for the i-th dosing interval (C2h,i (i=10,11,12))		Up to 98 hours after first drug administration
Terminal half life of the analyte in plasma (t1/2)		Up to 168 hours after first drug administration
Percent swing of peak/trough concentrations of the analyte in plasma for the i-th dosing interval (%Swingi)	Calculated: (C2h,i - Cpre,i) / Cpre,i * 100% (i=10,11,12)	Up to 168 hours after first drug administration
Percent peak-trough fluctuation for the 13th dosing interval (%PTF13)	Calculated: (Cmax,ss,13 - Cpre,ss,13) * 8h / AUCss,13 * 100%)	Up to 168 hours after first drug administration
Percent fluctuation of area under the plasma concentration-time curve (AUCfluc,13)	Calculated: (AUCabove,13 - AUCbelow,13) / AUCabove,13	Up to 168 hours after first drug administration
Fibrinogen receptor occupancy levels		Up to 168 hours after first drug administration
Number of patients with clinically relevant findings in laboratory tests		up to 168 hours after first drug administration
Number of patients with clinically relevant findings in vital signs	systolic and diastolic blood pressure, pulse rate	up to day 8 after first drug administration
Number of patients with adverse events		Up to 3 days after last drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 1998
• Primary Completion (Actual): June 1, 1998

Study Registration Dates

• First Submitted: October 13, 2014
• First Submitted That Met QC Criteria: October 13, 2014
• First Posted (Estimate): October 15, 2014

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 13, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pantoprazole
• Other Study ID Numbers: 509.118