Drug-drug Interaction Study of Aggrenox and Omeprazole in Normal Volunteers

Drug-drug Interaction Study of the Effect of Omeprazole 80 mg q.d. at Steady State on the Pharmacokinetics and Pharmacodynamics of Aggrenox® Every 12 Hours at Steady State in Healthy Male and Female Volunteers (an Open-label, Randomised, Crossover Study)

The objective of the current study is to investigate if a drug-drug interaction occurs with the administration of omeprazole 80 mg q.d. at steady state on the pharmacokinetics of dipyridamole and the pharmacodynamics of ASA-induced platelet aggregation inhibition (components of Aggrenox®) when administered every 12 hours at steady state.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Aggrenox alone; Drug: Aggrenox and omeprazole; Drug: Omeprazole alone

Detailed Description

Purpose:

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States
      • 9.197.001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Healthy males and females according to the following criteria:

   Based upon a complete medical history, including the physical examination, vital signs (blood pressure(BP), pulse rate (PR)), 12-lead ECG, clinical laboratory tests

2. BMI >18.5 and BMI <32 kg/m2 (Body Mass Index)

Exclusion criteria:

1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance in the opinion of the PI
2. Any evidence of a clinically relevant concomitant disease
3. Clinically significant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hormonal, or hematologic (including a history of abnormal bruising) disorders in the opinion of the PI
4. Surgery of the gastrointestinal tract that might impair drug absorption
5. Clinically significant diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
6. History of relevant orthostatic hypotension, fainting spells or blackouts.
7. Chronic or relevant acute infections
8. History of relevant allergy/hypersensitivity (including allergy to study drugs or its excipients, or reactions to related drugs [e.g., non-steroidal anti-inflammatory drugs])
9. Intake of drugs with a long half-life (¿24 hours) within one month, or less than 10 half lives of the respective drug, prior to study drug administration or during the trial
10. Use of drugs which might reasonably influence the results of the trial (including OTC antacids) based on the knowledge at the time of protocol preparation within 14 days prior to administration or during the trial
11. Participation in another trial with an investigational drug within two months prior to administration or during the trial
12. Tobacco use within the 90 days prior to check-in and throughout the study
13. Alcohol abuse within the past 2 years
14. Drug abuse within the past 2 years
15. Blood donation or other significant blood loss within 56 days (inclusive) prior to screening, or plasma donation within 7 days (inclusive) prior to study drug administration, or during the trial
16. Excessive physical activities (within one week prior to first drug administration or during the trial)
17. Any laboratory value outside the reference range that is of clinical relevance in the opinion of the PI; including positive virology, or urine drug screen, or positive fecal occult blood test
18. Inability to comply with dietary regimen of trial site
19. In the opinion of the investigator it would be in the best interest of the subject to be excluded from participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A; Aggrenox alone	Drug: Aggrenox alone; Aggrenox 1 capsule twice daily for 7 days
Experimental: Treatment B; Aggrenox and omeprazole	Drug: Aggrenox and omeprazole; Aggrenox 1 capsule twice daily and omeprazole 80mg once daily for 7 days
Active Comparator: Treatment C; Omeprazole alone	Drug: Omeprazole alone; omeprazole 80 once daily for 7 days
Experimental: Treatment D; Aggrenox and omeprazole	Drug: Aggrenox and omeprazole; Aggrenox 1 capsule twice daily and omeprazole 80mg once daily for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Dipyridamole Maximum Concentration (Cmax)	Maximum measured concentration of dipyridamole in plasma	7 days
Plasma Dipyridamole Area Under Plasma Concentration-time Curve From Zero to 12 Hours (AUC0-12)	Area under the concentration time curve of the analyte in plasma from 0 to 12 hours at steady state	7 days
Inhibition of Platelet Aggregation at 4 Hours Post Dose (IPA4)	IPA4 equals the platelet aggregation measured 4 hours post dose divided by the platelet aggregation measured at baseline (multiplied by 100).	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Dipyridamole Minimum Concentration (Cmin)	Minimum measured concentration of dipyridamole in plasma	7 days
Inhibition of Platelet Aggregation at 12 Hours Post Dose (IPA12)	IPA12 equals the platelet aggregation measured 12 hours post dose divided by the platelet aggregation measured at baseline (multiplied by 100).	7 days
Percentage Peak-to-trough Fluctuation (%PTF)	PTF = 100*((Cmax-Cmin)/Cavg) where Cavg=(AUC0-12)/12.	7 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: February 23, 2011
• First Submitted That Met QC Criteria: February 23, 2011
• First Posted (Estimate): February 24, 2011

Study Record Updates

• Last Update Posted (Estimate): December 24, 2013
• Last Update Submitted That Met QC Criteria: November 27, 2013
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole; Aspirin, Dipyridamole Drug Combination
• Other Study ID Numbers: 9.197