Trial Outcomes & Findings for Drug-drug Interaction Study of Aggrenox and Omeprazole in Normal Volunteers (NCT NCT01303445)
NCT ID: NCT01303445
Last Updated: 2013-12-24
Results Overview
Maximum measured concentration of dipyridamole in plasma
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
60 participants
Primary outcome timeframe
7 days
Results posted on
2013-12-24
Participant Flow
Participant milestones
| Measure |
ABCD Sequence
Aggrenox/Aggrenox+Omeprazole/Omeprazole/Aggrenox+Omeprazole
|
CDAB Sequence
Omeprazole/Aggrenox+Omeprazole/Aggrenox/Aggrenox+Omeprazole
|
|---|---|---|
|
First Intervention (7 Days)
STARTED
|
30
|
30
|
|
First Intervention (7 Days)
COMPLETED
|
29
|
30
|
|
First Intervention (7 Days)
NOT COMPLETED
|
1
|
0
|
|
Second Intervention (7 Days)
STARTED
|
29
|
30
|
|
Second Intervention (7 Days)
COMPLETED
|
28
|
28
|
|
Second Intervention (7 Days)
NOT COMPLETED
|
1
|
2
|
|
Washout (14 Days)
STARTED
|
28
|
28
|
|
Washout (14 Days)
COMPLETED
|
27
|
26
|
|
Washout (14 Days)
NOT COMPLETED
|
1
|
2
|
|
Third Intervention (7 Days)
STARTED
|
27
|
26
|
|
Third Intervention (7 Days)
COMPLETED
|
27
|
26
|
|
Third Intervention (7 Days)
NOT COMPLETED
|
0
|
0
|
|
Fourth Intervention (7 Days)
STARTED
|
27
|
26
|
|
Fourth Intervention (7 Days)
COMPLETED
|
26
|
26
|
|
Fourth Intervention (7 Days)
NOT COMPLETED
|
1
|
0
|
|
Follow-up Period (14 Days)
STARTED
|
26
|
26
|
|
Follow-up Period (14 Days)
COMPLETED
|
26
|
25
|
|
Follow-up Period (14 Days)
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
ABCD Sequence
Aggrenox/Aggrenox+Omeprazole/Omeprazole/Aggrenox+Omeprazole
|
CDAB Sequence
Omeprazole/Aggrenox+Omeprazole/Aggrenox/Aggrenox+Omeprazole
|
|---|---|---|
|
First Intervention (7 Days)
Withdrawal by Subject
|
1
|
0
|
|
Second Intervention (7 Days)
Adverse Event
|
0
|
2
|
|
Second Intervention (7 Days)
Withdrawal by Subject
|
1
|
0
|
|
Washout (14 Days)
Protocol Violation
|
1
|
0
|
|
Washout (14 Days)
Lost to Follow-up
|
0
|
2
|
|
Fourth Intervention (7 Days)
Withdrawal by Subject
|
1
|
0
|
|
Follow-up Period (14 Days)
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Drug-drug Interaction Study of Aggrenox and Omeprazole in Normal Volunteers
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=60 Participants
|
|---|---|
|
Age, Continuous
|
35.3 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
57 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black / African American
|
3 participants
n=5 Participants
|
|
Weight
|
75.69 kilograms
n=5 Participants
|
|
Body Mass Index (BMI)
|
26.81 kilograms per square meter
n=5 Participants
|
PRIMARY outcome
Timeframe: 7 daysPopulation: 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.
Maximum measured concentration of dipyridamole in plasma
Outcome measures
| Measure |
Aggrenox Alone BID
n=55 Participants
Aggrenox (aspirin/extended release dipyridamole) 25mg/200mg capsules BID (twice daily)
|
Aggrenox BID Plus Omeprazole QD Following Aggrenox Alone
n=54 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Aggrenox alone
|
Aggrenox BID Plus Omeprazole QD Following Omeprazole Alone
n=54 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Omeprazole alone
|
Omeprazole Alone QD
Omeprazole 40mg QD (once daily)
|
|---|---|---|---|---|
|
Plasma Dipyridamole Maximum Concentration (Cmax)
|
2750 nanogram/milliliter
Geometric Coefficient of Variation 30.4
|
2550 nanogram/milliliter
Geometric Coefficient of Variation 27.5
|
2550 nanogram/milliliter
Geometric Coefficient of Variation 29.1
|
—
|
PRIMARY outcome
Timeframe: 7 daysPopulation: 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.
Area under the concentration time curve of the analyte in plasma from 0 to 12 hours at steady state
Outcome measures
| Measure |
Aggrenox Alone BID
n=55 Participants
Aggrenox (aspirin/extended release dipyridamole) 25mg/200mg capsules BID (twice daily)
|
Aggrenox BID Plus Omeprazole QD Following Aggrenox Alone
n=53 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Aggrenox alone
|
Aggrenox BID Plus Omeprazole QD Following Omeprazole Alone
n=54 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Omeprazole alone
|
Omeprazole Alone QD
Omeprazole 40mg QD (once daily)
|
|---|---|---|---|---|
|
Plasma Dipyridamole Area Under Plasma Concentration-time Curve From Zero to 12 Hours (AUC0-12)
|
17100 (nanogram/milliliter)*hours
Geometric Coefficient of Variation 33.7
|
16700 (nanogram/milliliter)*hours
Geometric Coefficient of Variation 28.4
|
16500 (nanogram/milliliter)*hours
Geometric Coefficient of Variation 31.1
|
—
|
PRIMARY outcome
Timeframe: 7 daysPopulation: 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.
IPA4 equals the platelet aggregation measured 4 hours post dose divided by the platelet aggregation measured at baseline (multiplied by 100).
Outcome measures
| Measure |
Aggrenox Alone BID
n=55 Participants
Aggrenox (aspirin/extended release dipyridamole) 25mg/200mg capsules BID (twice daily)
|
Aggrenox BID Plus Omeprazole QD Following Aggrenox Alone
n=54 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Aggrenox alone
|
Aggrenox BID Plus Omeprazole QD Following Omeprazole Alone
n=54 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Omeprazole alone
|
Omeprazole Alone QD
Omeprazole 40mg QD (once daily)
|
|---|---|---|---|---|
|
Inhibition of Platelet Aggregation at 4 Hours Post Dose (IPA4)
|
97.89 percent of baseline platelet aggregation
Standard Deviation 2.74
|
96.34 percent of baseline platelet aggregation
Standard Deviation 4.21
|
97.02 percent of baseline platelet aggregation
Standard Deviation 2.69
|
—
|
SECONDARY outcome
Timeframe: 7 daysPopulation: 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.
Minimum measured concentration of dipyridamole in plasma
Outcome measures
| Measure |
Aggrenox Alone BID
n=55 Participants
Aggrenox (aspirin/extended release dipyridamole) 25mg/200mg capsules BID (twice daily)
|
Aggrenox BID Plus Omeprazole QD Following Aggrenox Alone
n=54 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Aggrenox alone
|
Aggrenox BID Plus Omeprazole QD Following Omeprazole Alone
n=54 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Omeprazole alone
|
Omeprazole Alone QD
Omeprazole 40mg QD (once daily)
|
|---|---|---|---|---|
|
Plasma Dipyridamole Minimum Concentration (Cmin)
|
679 nanogram/milliliter
Geometric Coefficient of Variation 47.1
|
723 nanogram/milliliter
Geometric Coefficient of Variation 41.8
|
713 nanogram/milliliter
Geometric Coefficient of Variation 46.5
|
—
|
SECONDARY outcome
Timeframe: 7 daysPopulation: 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.
IPA12 equals the platelet aggregation measured 12 hours post dose divided by the platelet aggregation measured at baseline (multiplied by 100).
Outcome measures
| Measure |
Aggrenox Alone BID
n=55 Participants
Aggrenox (aspirin/extended release dipyridamole) 25mg/200mg capsules BID (twice daily)
|
Aggrenox BID Plus Omeprazole QD Following Aggrenox Alone
n=54 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Aggrenox alone
|
Aggrenox BID Plus Omeprazole QD Following Omeprazole Alone
n=54 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Omeprazole alone
|
Omeprazole Alone QD
Omeprazole 40mg QD (once daily)
|
|---|---|---|---|---|
|
Inhibition of Platelet Aggregation at 12 Hours Post Dose (IPA12)
|
98.78 percent of baseline platelet aggregation
Standard Deviation 2.53
|
97.80 percent of baseline platelet aggregation
Standard Deviation 3.00
|
98.11 percent of baseline platelet aggregation
Standard Deviation 2.98
|
—
|
SECONDARY outcome
Timeframe: 7 daysPopulation: 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.
PTF = 100\*((Cmax-Cmin)/Cavg) where Cavg=(AUC0-12)/12.
Outcome measures
| Measure |
Aggrenox Alone BID
n=55 Participants
Aggrenox (aspirin/extended release dipyridamole) 25mg/200mg capsules BID (twice daily)
|
Aggrenox BID Plus Omeprazole QD Following Aggrenox Alone
n=53 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Aggrenox alone
|
Aggrenox BID Plus Omeprazole QD Following Omeprazole Alone
n=54 Participants
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Omeprazole alone
|
Omeprazole Alone QD
Omeprazole 40mg QD (once daily)
|
|---|---|---|---|---|
|
Percentage Peak-to-trough Fluctuation (%PTF)
|
144 percent of average hourly plasma conc.
Standard Deviation 31.8
|
132 percent of average hourly plasma conc.
Standard Deviation 41.4
|
134 percent of average hourly plasma conc.
Standard Deviation 41.2
|
—
|
Adverse Events
Aggrenox Alone BID
Serious events: 0 serious events
Other events: 41 other events
Deaths: 0 deaths
Aggrenox BID Plus Omeprazole QD Following Aggrenox Alone
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Omeprazole Alone QD
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Aggrenox BID Plus Omeprazole QD Following Omeprazole Alone
Serious events: 0 serious events
Other events: 48 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Aggrenox Alone BID
n=56 participants at risk
Aggrenox (aspirin/extended release dipyridamole) 25mg/200mg capsules BID (twice daily)
|
Aggrenox BID Plus Omeprazole QD Following Aggrenox Alone
n=55 participants at risk
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Aggrenox alone
|
Omeprazole Alone QD
n=57 participants at risk
Omeprazole 40mg QD (once daily)
|
Aggrenox BID Plus Omeprazole QD Following Omeprazole Alone
n=57 participants at risk
Aggrenox 25mg/200mg capsules BID plus Omeprazole 40mg QD (once daily) following Omeprazole alone
|
|---|---|---|---|---|
|
Cardiac disorders
Palpitations
|
5.4%
3/56 • 6 weeks
|
0.00%
0/55 • 6 weeks
|
3.5%
2/57 • 6 weeks
|
3.5%
2/57 • 6 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
5.4%
3/56 • 6 weeks
|
0.00%
0/55 • 6 weeks
|
1.8%
1/57 • 6 weeks
|
0.00%
0/57 • 6 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
10.7%
6/56 • 6 weeks
|
7.3%
4/55 • 6 weeks
|
3.5%
2/57 • 6 weeks
|
10.5%
6/57 • 6 weeks
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/56 • 6 weeks
|
1.8%
1/55 • 6 weeks
|
5.3%
3/57 • 6 weeks
|
0.00%
0/57 • 6 weeks
|
|
Gastrointestinal disorders
Nausea
|
33.9%
19/56 • 6 weeks
|
0.00%
0/55 • 6 weeks
|
7.0%
4/57 • 6 weeks
|
24.6%
14/57 • 6 weeks
|
|
Gastrointestinal disorders
Vomiting
|
21.4%
12/56 • 6 weeks
|
3.6%
2/55 • 6 weeks
|
3.5%
2/57 • 6 weeks
|
24.6%
14/57 • 6 weeks
|
|
General disorders
Chest discomfort
|
10.7%
6/56 • 6 weeks
|
1.8%
1/55 • 6 weeks
|
1.8%
1/57 • 6 weeks
|
7.0%
4/57 • 6 weeks
|
|
General disorders
Chills
|
1.8%
1/56 • 6 weeks
|
1.8%
1/55 • 6 weeks
|
5.3%
3/57 • 6 weeks
|
1.8%
1/57 • 6 weeks
|
|
Injury, poisoning and procedural complications
Contusion
|
5.4%
3/56 • 6 weeks
|
3.6%
2/55 • 6 weeks
|
1.8%
1/57 • 6 weeks
|
3.5%
2/57 • 6 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.6%
2/56 • 6 weeks
|
1.8%
1/55 • 6 weeks
|
7.0%
4/57 • 6 weeks
|
0.00%
0/57 • 6 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
32.1%
18/56 • 6 weeks
|
7.3%
4/55 • 6 weeks
|
3.5%
2/57 • 6 weeks
|
35.1%
20/57 • 6 weeks
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.4%
3/56 • 6 weeks
|
0.00%
0/55 • 6 weeks
|
3.5%
2/57 • 6 weeks
|
1.8%
1/57 • 6 weeks
|
|
Nervous system disorders
Dizziness
|
12.5%
7/56 • 6 weeks
|
5.5%
3/55 • 6 weeks
|
3.5%
2/57 • 6 weeks
|
17.5%
10/57 • 6 weeks
|
|
Nervous system disorders
Headache
|
69.6%
39/56 • 6 weeks
|
10.9%
6/55 • 6 weeks
|
12.3%
7/57 • 6 weeks
|
71.9%
41/57 • 6 weeks
|
|
Nervous system disorders
Paraesthesia
|
5.4%
3/56 • 6 weeks
|
0.00%
0/55 • 6 weeks
|
3.5%
2/57 • 6 weeks
|
1.8%
1/57 • 6 weeks
|
|
Nervous system disorders
Somnolence
|
1.8%
1/56 • 6 weeks
|
1.8%
1/55 • 6 weeks
|
7.0%
4/57 • 6 weeks
|
1.8%
1/57 • 6 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
12.5%
7/56 • 6 weeks
|
1.8%
1/55 • 6 weeks
|
0.00%
0/57 • 6 weeks
|
1.8%
1/57 • 6 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/56 • 6 weeks
|
3.6%
2/55 • 6 weeks
|
1.8%
1/57 • 6 weeks
|
5.3%
3/57 • 6 weeks
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/56 • 6 weeks
|
0.00%
0/55 • 6 weeks
|
0.00%
0/57 • 6 weeks
|
5.3%
3/57 • 6 weeks
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER