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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.
Purpose:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Active Comparator | Aggrenox alone |
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| Treatment B | Experimental | Aggrenox and omeprazole |
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| Treatment C | Active Comparator | Omeprazole alone |
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| Treatment D | Experimental | Aggrenox and omeprazole |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aggrenox alone | Drug | Aggrenox 1 capsule twice daily for 7 days |
| |
| 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 |
| 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). |
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Inclusion criteria:
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
BMI >18.5 and BMI <32 kg/m2 (Body Mass Index)
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 9.197.001 Boehringer Ingelheim Investigational Site | Tempe | Arizona | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | ABCD Sequence | Aggrenox/Aggrenox+Omeprazole/Omeprazole/Aggrenox+Omeprazole |
| FG001 | CDAB Sequence | Omeprazole/Aggrenox+Omeprazole/Aggrenox/Aggrenox+Omeprazole |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (7 Days) |
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| Second Intervention (7 Days) |
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| Washout (14 Days) |
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| Third Intervention (7 Days) |
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| Fourth Intervention (7 Days) |
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| Follow-up Period (14 Days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Plasma Dipyridamole Maximum Concentration (Cmax) | Maximum measured concentration of dipyridamole in plasma | The pharmacokinetic data set (PK set) and the pharmacodynamic data set (PD set) include all treated subjects with data that do not have a relevant protocol violation (relevant to PK or PD). No data collected for Omeprazole arm since no plasma dipyridamole was expected for this treatment. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter | 7 days |
|
6 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Aggrenox Alone BID | Aggrenox (aspirin/extended release dipyridamole) 25mg/200mg capsules BID (twice daily) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D000068342 | Aspirin, Dipyridamole Drug Combination |
| D009853 | Omeprazole |
| ID | Term |
|---|---|
| D001241 | Aspirin |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 |
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| Aggrenox and omeprazole |
| Drug |
Aggrenox 1 capsule twice daily and omeprazole 80mg once daily for 7 days |
|
| Aggrenox and omeprazole | Drug | Aggrenox 1 capsule twice daily and omeprazole 80mg once daily for 7 days |
|
| Omeprazole alone | Drug | omeprazole 80 once daily for 7 days |
|
| 7 days |
| Percentage Peak-to-trough Fluctuation (%PTF) | PTF = 100*((Cmax-Cmin)/Cavg) where Cavg=(AUC0-12)/12. | 7 days |
| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Weight | Mean | Full Range | kilograms |
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| Body Mass Index (BMI) | Mean | Full Range | kilograms per square meter |
|
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Aggrenox alone
| OG002 | Aggrenox BID Plus Omeprazole QD Following Omeprazole Alone | Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Omeprazole alone |
| OG003 | Omeprazole Alone QD | Omeprazole 40mg QD (once daily) |
|
|
|
| Primary | 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 | The pharmacokinetic data set (PK set) and the pharmacodynamic data set (PD set) include all treated subjects with data that do not have a relevant protocol violation (relevant to PK or PD). No data collected for Omeprazole arm since no plasma dipyridamole was expected for this treatment. | Posted | Geometric Mean | Geometric Coefficient of Variation | (nanogram/milliliter)*hours | 7 days |
|
|
|
|
| Primary | 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). | The pharmacokinetic data set (PK set) and the pharmacodynamic data set (PD set) include all treated subjects with data that do not have a relevant protocol violation (relevant to PK or PD). No data collected for Omeprazole arm since no platelet inhibition was expected for this treatment. | Posted | Mean | Standard Deviation | percent of baseline platelet aggregation | 7 days |
|
|
|
|
| Secondary | Plasma Dipyridamole Minimum Concentration (Cmin) | Minimum measured concentration of dipyridamole in plasma | The pharmacokinetic data set (PK set) and the pharmacodynamic data set (PD set) include all treated subjects with data that do not have a relevant protocol violation (relevant to PK or PD). No data collected for Omeprazole arm since no plasma dipyridamole was expected for this treatment. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter | 7 days |
|
|
|
|
| Secondary | 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). | The pharmacokinetic data set (PK set) and the pharmacodynamic data set (PD set) include all treated subjects with data that do not have a relevant protocol violation (relevant to PK or PD). No data collected for Omeprazole arm since no platelet inhibition was expected for this treatment. | Posted | Mean | Standard Deviation | percent of baseline platelet aggregation | 7 days |
|
|
|
|
| Secondary | Percentage Peak-to-trough Fluctuation (%PTF) | PTF = 100*((Cmax-Cmin)/Cavg) where Cavg=(AUC0-12)/12. | The pharmacokinetic data set (PK set) and the pharmacodynamic data set (PD set) include all treated subjects with data that do not have a relevant protocol violation (relevant to PK or PD). No data collected for Omeprazole arm since no plasma dipyridamole was expected for this treatment. | Posted | Mean | Standard Deviation | percent of average hourly plasma conc. | 7 days |
|
|
|
| 0 |
| 56 |
| 41 |
| 56 |
| EG001 | Aggrenox BID Plus Omeprazole QD Following Aggrenox Alone | Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Aggrenox alone | 0 | 55 | 15 | 55 |
| EG002 | Omeprazole Alone QD | Omeprazole 40mg QD (once daily) | 0 | 57 | 17 | 57 |
| EG003 | Aggrenox BID Plus Omeprazole QD Following Omeprazole Alone | Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Omeprazole alone | 0 | 57 | 48 | 57 |
| Abdominal pain | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Chest discomfort | General disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Chills | General disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA Version 14.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA Version 14.0 | Systematic Assessment |
|
Other - Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004176 | Dipyridamole |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D011725 | Pyridines |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Comparison of Aggrenox + Omeprazole following Aggrenox versus Aggrenox alone |
| Percent Mean Ratio |
| 97.03 |
| 95 |
| 93.26 |
| 100.95 |
| Yes |
| Non-Inferiority or Equivalence |
Bioequivalence was established if the 90% confidence interval of the mean ratio fell within the 80 to 125% target range. |
Comparison of Aggrenox + Omeprazole following Aggrenox versus Aggrenox alone |
| Percent Mean Ratio |
| 98.42 |
| 90 |
| 97.66 |
| 99.18 |
| Yes |
| Non-Inferiority or Equivalence |
Bioequivalence was established if the 90% confidence interval of the mean ratio fell within the 80 to 125% target range. |
Comparison of Aggrenox + Omeprazole following Aggrenox versus Aggrenox alone |
| Percent Mean Ratio |
| 106.09 |
| 90 |
| 98.64 |
| 114.09 |
| Yes |
| Non-Inferiority or Equivalence |
Bioequivalence was established if the 90% confidence interval of the mean ratio fell within the 80 to 125% target range. |
Comparison of Aggrenox + Omeprazole following Aggrenox versus Aggrenox alone |
| Percent Mean Ratio |
| 99.02 |
| 90 |
| 98.46 |
| 99.59 |
| Yes |
| Non-Inferiority or Equivalence |
Bioequivalence was established if the 90% confidence interval of the mean ratio fell within the 80 to 125% target range. |