A Study of the Effects of Multiple Doses of Dexlansoprazole, Lansoprazole, Omeprazole or Esomeprazole on the Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Participants.
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the potential effect and safety of multiple oral doses of dexlansoprazole, lansoprazole, omeprazole or esomeprazole, once daily (QD), on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel, and to assess the safety of multiple doses of clopidogrel in healthy participants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is a Phase 1, randomized, open-label, single-center, multiple-dose, 2-period, crossover study to assess the effects of multiple oral doses of dexlansoprazole, lansoprazole, omeprazole or esomeprazole on the steady-state pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel in healthy participants.
Participants were randomized equally into eight regimen sequence groups, 20 participants each. Participants randomized to Sequence Groups 1 and 2, 3 and 4, 5 and 6 and 7 and 8 were called proton pump inhibitor (PPI) Groups 1, 2, 3, and 4, respectively. Each sequence group consists of 2 regimens. Sequence Groups 1, 3, 5 and 7 dosed Regimen A (75 mg clopidogrel) for Days 1-9 of Period 1 and then crossed over to one of the following 4 regimens for Days 1-9 of Period 2: Regimen B (75 mg clopidogrel + 30 mg lansoprazole), Regimen C (75 mg clopidogrel + 60 mg dexlansoprazole), Regimen D (75 mg clopidogrel + 80 mg [2x40 mg] omeprazole), or Regimen E (75 mg clopidogrel + 40 mg esomeprazole). Sequence Groups 2, 4, 6 and 8 began with either Regimen B, C, D or E for Period 1 and then crossed over to Regimen A for Period 2.
On Day 9 of each period, blood samples were collected at predose and for 24 hours postdose to measure plasma concentrations of the active metabolite of clopidogrel. Platelet function was assessed daily prior to the dose of clopidogrel on Days 7-9 and 24-hours post Day 9 dose in each period. There was a washout interval of 10 to 14 days between the last dose of study drug in Period 1 and the first dose of study drug in Period 2.
Study participants were confined to the study center for 10 consecutive nights in Period 1, followed by a 10- to 14-day washout interval and confined for an additional 10 consecutive nights in Period 2.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Regimen A Clopidogrel 75 mg QD |
Drug: Clopidogrel
Clopidogrel 75 mg, tablets, orally, once daily days 1-9.
Other Names:
|
| Other: Regimen B Clopidogrel 75 mg QD and Lansoprazole 30 mg QD |
Drug: Clopidogrel and Lansoprazole
Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily days 1-9.
Other Names:
|
| Other: Regimen C Clopidogrel 75 mg QD and Dexlansoprazole 60 mg QD |
Drug: Clopidogrel and Dexlansoprazole
Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily days 1-9.
Other Names:
|
| Other: Regimen D Clopidogrel 75 mg QD and Omeprazole 80 mg QD |
Drug: Clopidogrel and Omeprazole
Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily days 1-9.
Other Names:
|
| Other: Regimen E Clopidogrel 75 mg QD and Esomeprazole 40 mg QD |
Drug: Clopidogrel and Esomeprazole
Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily days 1-9.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetic Parameter Peak Plasma Concentration (Cmax) of Clopidogrel's Active Metabolite. [Day 9 of each period]
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
- Pharmacokinetic Parameter Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]) of Clopidogrel's Active Metabolite. [Day 9 of each period]
Area under the plasma concentration versus time curve (AUC(0-tlqc)) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]).
- Pharmacodynamic Parameter Platelet Reactivity Index (PRI) From Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation State (Flow Cytometry). [24-hour post Day 9 dose in each period.]
PRI is the platelet reactivity index from VASP phosphorylation state (flow cytometry).
- Pharmacodynamic Parameter Maximum Platelet Aggregation (MPA) From Aggregometry (Turbidimetric) With 5 µM Adenosine Diphosphate. [24-hour post Day 9 dose in each period.]
Maximum platelet aggregation (MPA) from aggregometry (turbidimetric) with 5 µM adenosine diphosphate.
- Pharmacodynamic Parameter MPA From Aggregometry (Turbidimetric) With 20 µM Adenosine Diphosphate. [24-hour post Day 9 dose in each period.]
MPA from aggregometry (turbidimetric) with 20 µM adenosine diphosphate.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
The participant or the participant's legally acceptable representative signs a written, informed consent form prior to the initiation of any study procedures.
-
Weighs at least 50 kg and has a body mass index (BMI) between 18 and 30 kg/m2, inclusive, at Screening and Check-in (Day -1 of Period 1) Visits.
-
Must be a CYP2C19 extensive metabolizer (wt/wt).
-
Females cannot be nursing and must have a negative urine pregnancy test at Day -1 or be of non-childbearing potential. If females are of child bearing potential, must have a negative serum human chorionic gonadotropin (hCG) pregnancy test during Screening and on an acceptable form of contraception, or have had bilateral tubal ligation if performed a minimum of 90 days prior to Day 1.
-
At the Screening and Check-in (Day -1 of Period 1) Visits, must have an estimated creatinine clearance (CLcr) greater than or equal 90 mL/minute as determined from the Cockcroft-Gault formula.
-
Is in good health as determined by a physician based upon medical history, electrocardiogram, and physical examination findings at the Screening and Check-in (Day -1 of Period 1) Visits.
-
Participant's clinical laboratory evaluations (including hematology, clinical chemistry [fasted for a least 8 hours], and urinalysis) at the Screening and Check-in (Day -1 of Period 1) Visits are within the reference range for the testing laboratory or are deemed not clinically significant by the investigator and TGRD Medical Monitor.
-
Participant's urine drug screen for selected substances of abuse is negative at the Screening and Check-in (Day -1 of Period 1) Visits.
Exclusion Criteria:
-
Has consumed products containing Seville oranges (sour), grapefruit or grapefruit juice within 14 days prior to the first dose of study drug or is unwilling to agree to abstain from products containing Seville oranges (sour), grapefruit or grapefruit juice while participating in the study.
-
Has current or recent (within 6 months) gastrointestinal disease, a history of malabsorption, esophageal reflux, gastric bleeding or peptic ulcer disease, frequent (more than once per week) occurrence of heartburn, or any surgical intervention (eg, cholecystectomy), which would be expected to influence the absorption of drugs.
-
Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as the consumption of more than 4 alcoholic beverages per day) within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
-
Is currently participating in another investigational study or has received any investigational compound within 30 days prior to the Check-in (Day -1 of Period 1) Visit.
-
Has received any known hepatic or renal clearance altering agents (eg, erythromycin, cimetidine, barbiturates, phenothiazines, fluvoxamine, etc.) within 28 days prior to first dose of study drug.
-
Has a history or clinical manifestations of significant metabolic, hematologic, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urologic, immunologic, or psychiatric disorder as determined by the investigator which may impact the ability of the participant to take part in or potentially confound the trial results.
-
Has a history of hypersensitivity or allergies to any drug or food or any excipients of clopidogrel, lansoprazole, dexlansoprazole, omeprazole, esomeprazole or other drug with the same mechanism of action or related compounds.
-
Has had an acute, clinically significant illness within 30 days prior to the first dose of study drug.
-
Has a systolic blood pressure greater than 140 mm Hg or has a diastolic blood pressure greater than 90 mm Hg at Screening or Check-in (Day -1 of Period 1).
-
Has a positive test result for hepatitis B surface antigen (HBsAg) or antibody to hepatitis C virus (anti-HCV) at Screening, or a known history of infection with the human immunodeficiency virus (HIV).
-
Has a Day -1 laboratory value assessed by the principal investigator and sponsor medical monitor as clinically significant underlying disease or condition that may prevent the participant from entering the study.
-
Has an alanine aminotransferase, aspartate aminotransferase or Total Bilirubin level that exceeds the upper limit of normal at the Screening or Check-in (Day -1 of Period
- Visits.
-
Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 6 weeks prior to Check-in (Day -1 of Period 1) Visit, or has a positive cotinine screen at the Screening or Check-in (Day - 1 of Period 1) Visits or anticipates an inability to abstain from these products for the duration of the study.
-
With the exception of acetaminophen, has taken any excluded medication, supplements or food products listed in the Excluded Dietary Items and Medications table located in the study protocol.
-
Has donated blood products (such as plasma) within 30 days, or has donated whole blood or had a significant blood loss (500 mL) within 56 days of the first dose of study drug
-
Has a positive test result for caffeine at the Check-in (Day -1 of Period 1) Visit.
-
Has a history of cancer, except basal cell carcinoma, which has not been in remission for at least 5 years prior to the first dose of study drug.
-
Has received clopidogrel or any PPIs or histamine2-receptor antagonists within 28 days of screening.
-
Participant, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tempe | Arizona | United States |
Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Medical Director Clinical Science, Takeda
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- TAK-390MR_101
- U1111-1112-6792
Study Results
Participant Flow
| Recruitment Details | Participants enrolled at one site in the United States from 15 December 2009 to 08 July 2010. |
|---|---|
| Pre-assignment Detail | Healthy participants were enrolled in one of 4, once-daily (QD), proton pump inhibitor (PPI) treatment groups. |
| Arm/Group Title | PPI Group 1 | PPI Group 2 | PPI Group 3 | PPI Group 4 |
|---|---|---|---|---|
| Arm/Group Description | Regimen A: Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. Regimen B: Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily for up to 9 days. | Regimen A: Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. Regimen C: Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily for up to 9 days. | Regimen A: Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. Regimen D: Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily for up to 9 days. | Regimen A: Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. Regimen E: Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily for up to 9 days. |
| Period Title: Overall Study | ||||
| STARTED | 40 | 40 | 40 | 40 |
| COMPLETED | 38 | 36 | 38 | 38 |
| NOT COMPLETED | 2 | 4 | 2 | 2 |
Baseline Characteristics
| Arm/Group Title | PPI Group 1 | PPI Group 2 | PPI Group 3 | PPI Group 4 | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Regimen A: Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. Regimen B: Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily for up to 9 days. | Regimen A: Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. Regimen C: Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily for up to 9 days. | Regimen A: Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. Regimen D: Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily for up to 9 days. | Regimen A: Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. Regimen E: Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily for up to 9 days. | Total of all reporting groups |
| Overall Participants | 40 | 40 | 40 | 40 | 160 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
32.8
(6.48)
|
35.7
(7.92)
|
34.0
(7.40)
|
33.3
(7.10)
|
33.9
(7.26)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
20
50%
|
20
50%
|
20
50%
|
20
50%
|
80
50%
|
| Male |
20
50%
|
20
50%
|
20
50%
|
20
50%
|
80
50%
|
Outcome Measures
| Title | Pharmacokinetic Parameter Peak Plasma Concentration (Cmax) of Clopidogrel's Active Metabolite. |
|---|---|
| Description | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. |
| Time Frame | Day 9 of each period |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who had valid parameter estimates for both regimens within a PPI group were included in the pharmacokinetics (PK) statistical analyses for this parameter. |
| Arm/Group Title | PPI Group 1: Regimen A | PPI Group 1: Regimen B | PPI Group 2: Regimen A | PPI Group 2: Regimen C | PPI Group 3: Regimen A | PPI Group 3: Regimen D | PPI Group 4: Regimen A | PPI Group 4: Regimen E |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily for up to 9 days. |
| Measure Participants | 38 | 38 | 36 | 36 | 38 | 38 | 38 | 38 |
| Mean (Standard Deviation) [ng/mL] |
39.14
(12.553)
|
30.01
(15.264)
|
38.85
(15.699)
|
29.33
(12.400)
|
38.25
(12.461)
|
22.55
(10.682)
|
40.98
(22.908)
|
24.69
(10.641)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 1: Regimen A, PPI Group 1: Regimen B |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.7000 | |
| Confidence Interval |
(2-Sided) 90% 0.6106 to 0.8026 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference refers to the point estimates of the relative bioavailability. With its confidence intervals, it was obtained from the ANOVA model on the natural logarithm transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 2: Regimen A, PPI Group 2: Regimen C |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.7340 | |
| Confidence Interval |
(2-Sided) 90% 0.6516 to 0.8269 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference refers to the point estimates of the relative bioavailability. With its confidence intervals, it was obtained from the ANOVA model on the natural logarithm transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 3: Regimen A, PPI Group 3: Regimen D |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.5564 | |
| Confidence Interval |
(2-Sided) 90% 0.4877 to 0.6347 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference refers to the point estimates of the relative bioavailability. With its confidence intervals, it was obtained from the ANOVA model on the natural logarithm transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 4: Regimen A, PPI Group 4: Regimen E |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.6783 | |
| Confidence Interval |
(2-Sided) 90% 0.5063 to 0.9087 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference refers to the point estimates of the relative bioavailability. With its confidence intervals, it was obtained from the ANOVA model on the natural logarithm transformed data. | |
| Title | Pharmacokinetic Parameter Area Under the Plasma Concentration Versus Time Curve (AUC) From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]) of Clopidogrel's Active Metabolite. |
|---|---|
| Description | Area under the plasma concentration versus time curve (AUC(0-tlqc)) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]). |
| Time Frame | Day 9 of each period |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who had valid parameter estimates for both formulations within PPI groups were included in the PK statistical analyses for those parameters. |
| Arm/Group Title | PPI Group 1: Regimen A | PPI Group 1: Regimen B | PPI Group 2: Regimen A | PPI Group 2: Regimen C | PPI Group 3: Regimen A | PPI Group 3: Regimen D | PPI Group 4: Regimen A | PPI Group 4: Regimen E |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily for up to 9 days. |
| Measure Participants | 38 | 38 | 36 | 36 | 38 | 38 | 38 | 38 |
| Mean (Standard Deviation) [ng*hr/ML] |
41.69
(10.020)
|
36.42
(10.825)
|
41.25
(14.690)
|
37.75
(13.132)
|
37.78
(12.043)
|
26.28
(8.800)
|
42.35
(18.785)
|
31.23
(9.938)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 1: Regimen A, PPI Group 1: Regimen B |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.8573 | |
| Confidence Interval |
(2-Sided) 90% 0.8020 to 0.9165 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference refers to the point estimates of the relative bioavailability. With its confidence intervals, it was obtained from the ANOVA model on the natural logarithm transformed data. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 2: Regimen A, PPI Group 2: Regimen C |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.9103 | |
| Confidence Interval |
(2-Sided) 90% 0.8567 to 0.9672 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference refers to the point estimates of the relative bioavailability. With its confidence intervals, it was obtained from the ANOVA model on the natural logarithm transformed data. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 3: Regimen A, PPI Group 3: Regimen D |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.6943 | |
| Confidence Interval |
(2-Sided) 90% 0.6438 to 0.7487 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference refers to the point estimates of the relative bioavailability. With its confidence intervals, it was obtained from the ANOVA model on the natural logarithm transformed data. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 4: Regimen A, PPI Group 4: Regimen E |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.8389 | |
| Confidence Interval |
(2-Sided) 90% 0.6440 to 1.0928 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The mean difference refers to the point estimates of the relative bioavailability. With its confidence intervals, it was obtained from the ANOVA model on the natural logarithm transformed data. | |
| Title | Pharmacodynamic Parameter Platelet Reactivity Index (PRI) From Vasodilator-stimulated Phosphoprotein (VASP) Phosphorylation State (Flow Cytometry). |
|---|---|
| Description | PRI is the platelet reactivity index from VASP phosphorylation state (flow cytometry). |
| Time Frame | 24-hour post Day 9 dose in each period. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who had valid parameter estimates for both regimens within a PPI group were included in the pharmacodynamics (PD) statistical analyses for this parameter. |
| Arm/Group Title | PPI Group 1: Regimen A | PPI Group 1: Regimen B | PPI Group 2: Regimen A | PPI Group 2: Regimen C | PPI Group 3: Regimen A | PPI Group 3: Regimen D | PPI Group 4: Regimen A | PPI Group 4: Regimen E |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily for up to 9 days. |
| Measure Participants | 38 | 38 | 36 | 36 | 38 | 38 | 38 | 38 |
| Mean (Standard Deviation) [percent inhibition] |
42.3
(14.61)
|
46.4
(16.44)
|
41.3
(15.45)
|
43.0
(16.47)
|
47.9
(15.70)
|
59.1
(17.87)
|
46.5
(17.28)
|
58.0
(14.64)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 1: Regimen A, PPI Group 1: Regimen B |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 4.1016 | |
| Confidence Interval |
(2-Sided) 90% 0.0348 to 8.1684 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Included only participants with complete data for both regimens. Values are least squares mean difference. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 2: Regimen A, PPI Group 2: Regimen C |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.0474 | |
| Confidence Interval |
(2-Sided) 90% -0.8555 to 4.9503 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Included only participants with complete data for both regimens. Values are least squares mean difference. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 3: Regimen A, PPI Group 3: Regimen D |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 11.0407 | |
| Confidence Interval |
(2-Sided) 90% 6.5219 to 15.5595 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Included only participants with complete data for both regimens. Values are least squares mean difference. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 4: Regimen A, PPI Group 4: Regimen E |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 11.4437 | |
| Confidence Interval |
(2-Sided) 90% 7.1791 to 15.7083 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Included only participants with complete data for both regimens. Values are least squares mean difference. | |
| Title | Pharmacodynamic Parameter Maximum Platelet Aggregation (MPA) From Aggregometry (Turbidimetric) With 5 µM Adenosine Diphosphate. |
|---|---|
| Description | Maximum platelet aggregation (MPA) from aggregometry (turbidimetric) with 5 µM adenosine diphosphate. |
| Time Frame | 24-hour post Day 9 dose in each period. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who had valid parameter estimates for both formulations within PPI groups were included in the PD statistical analyses for those parameters. |
| Arm/Group Title | PPI Group 1: Regimen A | PPI Group 1: Regimen B | PPI Group 2: Regimen A | PPI Group 2: Regimen C | PPI Group 3: Regimen A | PPI Group 3: Regimen D | PPI Group 4: Regimen A | PPI Group 4: Regimen E |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily for up to 9 days. |
| Measure Participants | 38 | 38 | 36 | 36 | 37 | 37 | 38 | 38 |
| Mean (Standard Deviation) [percentage of MPA] |
28.1
(6.76)
|
30.8
(9.35)
|
34.6
(14.23)
|
36.2
(16.87)
|
34.2
(12.32)
|
42.5
(14.74)
|
29.3
(10.41)
|
38.2
(17.77)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 1: Regimen A, PPI Group 1: Regimen B |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.035 |
| Comments | From ANOVA models in which the least-square means between two regimens are compared. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 2: Regimen A, PPI Group 2: Regimen C |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.445 |
| Comments | From ANOVA models in which the least-square means between two regimens are compared. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 3: Regimen A, PPI Group 3: Regimen D |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | From ANOVA models in which the least-square means between two regimens are compared. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 4: Regimen A, PPI Group 4: Regimen E |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | From ANOVA models in which the least-square means between two regimens are compared. | |
| Method | ANOVA | |
| Comments | ||
| Title | Pharmacodynamic Parameter MPA From Aggregometry (Turbidimetric) With 20 µM Adenosine Diphosphate. |
|---|---|
| Description | MPA from aggregometry (turbidimetric) with 20 µM adenosine diphosphate. |
| Time Frame | 24-hour post Day 9 dose in each period. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who had valid parameter estimates for both formulations within PPI groups were included in the PK and PD statistical analyses for those parameters. |
| Arm/Group Title | PPI Group 1: Regimen A | PPI Group 1: Regimen B | PPI Group 2: Regimen A | PPI Group 2: Regimen C | PPI Group 3: Regimen A | PPI Group 3: Regimen D | PPI Group 4: Regimen A | PPI Group 4: Regimen E |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily for up to 9 days. |
| Measure Participants | 38 | 38 | 36 | 36 | 37 | 37 | 38 | 38 |
| Mean (Standard Deviation) [percentage of MPA] |
36.7
(9.11)
|
41.6
(12.65)
|
43.1
(13.24)
|
46.3
(16.93)
|
43.5
(14.00)
|
53.5
(13.75)
|
39.3
(13.22)
|
47.9
(15.77)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 1: Regimen A, PPI Group 1: Regimen B |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | From ANOVA models in which the least-square means between two regimens are compared. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 2: Regimen A, PPI Group 2: Regimen C |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.148 |
| Comments | From ANOVA models in which the least-square means between two regimens are compared. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 3: Regimen A, PPI Group 3: Regimen D |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | From ANOVA models in which the least-square means between two regimens are compared. | |
| Method | ANOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PPI Group 4: Regimen A, PPI Group 4: Regimen E |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | From ANOVA models in which the least-square means between two regimens are compared. | |
| Method | ANOVA | |
| Comments | ||
Adverse Events
| Time Frame | Treatment-emergent adverse events are adverse events that started or worsened after the first dose of study drug and within 30 days after the last dose of study drug. | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study drug. | |||||||||||||||
| Arm/Group Title | PPI Group 1: Regimen A | PPI Group 1: Regimen B | PPI Group 2: Regimen A | PPI Group 2: Regimen C | PPI Group 3: Regimen A | PPI Group 3: Regimen D | PPI Group 4: Regimen A | PPI Group 4: Regimen E | ||||||||
| Arm/Group Description | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Lansoprazole 30 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Dexlansoprazole 60 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Omeprazole 80 mg, capsules, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily for up to 9 days. | Clopidogrel 75 mg, tablets, orally, once daily and Esomeprazole 40 mg, capsules, orally, once daily for up to 9 days. | ||||||||
All Cause Mortality |
||||||||||||||||
| PPI Group 1: Regimen A | PPI Group 1: Regimen B | PPI Group 2: Regimen A | PPI Group 2: Regimen C | PPI Group 3: Regimen A | PPI Group 3: Regimen D | PPI Group 4: Regimen A | PPI Group 4: Regimen E | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||
Serious Adverse Events |
||||||||||||||||
| PPI Group 1: Regimen A | PPI Group 1: Regimen B | PPI Group 2: Regimen A | PPI Group 2: Regimen C | PPI Group 3: Regimen A | PPI Group 3: Regimen D | PPI Group 4: Regimen A | PPI Group 4: Regimen E | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | 0/40 (0%) | 0/40 (0%) | 1/40 (2.5%) | 0/40 (0%) | 0/40 (0%) | 0/40 (0%) | 0/40 (0%) | ||||||||
| Investigations | ||||||||||||||||
| Serum sickness-like reaction | 0/40 (0%) | 0/40 (0%) | 0/40 (0%) | 1/40 (2.5%) | 0/40 (0%) | 0/40 (0%) | 0/40 (0%) | 0/40 (0%) | ||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| PPI Group 1: Regimen A | PPI Group 1: Regimen B | PPI Group 2: Regimen A | PPI Group 2: Regimen C | PPI Group 3: Regimen A | PPI Group 3: Regimen D | PPI Group 4: Regimen A | PPI Group 4: Regimen E | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/39 (33.3%) | 16/39 (41%) | 19/39 (48.7%) | 16/38 (42.1%) | 14/40 (35%) | 11/38 (28.9%) | 17/39 (43.6%) | 15/39 (38.5%) | ||||||||
| Eye disorders | ||||||||||||||||
| Ocular hyperaemia | 0/39 (0%) | 0/39 (0%) | 0/39 (0%) | 2/38 (5.3%) | 0/40 (0%) | 0/38 (0%) | 1/39 (2.6%) | 0/39 (0%) | ||||||||
| Lacrimation increased | 0/39 (0%) | 0/39 (0%) | 0/39 (0%) | 0/38 (0%) | 2/40 (5%) | 0/38 (0%) | 0/39 (0%) | 0/39 (0%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal pain upper | 0/39 (0%) | 2/39 (5.1%) | 1/39 (2.6%) | 1/38 (2.6%) | 0/40 (0%) | 0/38 (0%) | 0/39 (0%) | 2/39 (5.1%) | ||||||||
| Nausea | 3/39 (7.7%) | 3/39 (7.7%) | 5/39 (12.8%) | 1/38 (2.6%) | 1/40 (2.5%) | 0/38 (0%) | 0/39 (0%) | 1/39 (2.6%) | ||||||||
| Abdominal pain lower | 0/39 (0%) | 0/39 (0%) | 1/39 (2.6%) | 2/38 (5.3%) | 1/40 (2.5%) | 1/38 (2.6%) | 3/39 (7.7%) | 0/39 (0%) | ||||||||
| Constipation | 1/39 (2.6%) | 0/39 (0%) | 2/39 (5.1%) | 1/38 (2.6%) | 1/40 (2.5%) | 1/38 (2.6%) | 1/39 (2.6%) | 2/39 (5.1%) | ||||||||
| Toothache | 0/39 (0%) | 1/39 (2.6%) | 1/39 (2.6%) | 2/38 (5.3%) | 0/40 (0%) | 0/38 (0%) | 0/39 (0%) | 0/39 (0%) | ||||||||
| Abdominal pain | 0/39 (0%) | 1/39 (2.6%) | 0/39 (0%) | 2/38 (5.3%) | 2/40 (5%) | 1/38 (2.6%) | 3/39 (7.7%) | 1/39 (2.6%) | ||||||||
| Abdominal distension | 0/39 (0%) | 1/39 (2.6%) | 1/39 (2.6%) | 1/38 (2.6%) | 0/40 (0%) | 0/38 (0%) | 0/39 (0%) | 2/39 (5.1%) | ||||||||
| General disorders | ||||||||||||||||
| Feeling Hot | 2/39 (5.1%) | 1/39 (2.6%) | 0/39 (0%) | 0/38 (0%) | 0/40 (0%) | 0/38 (0%) | 0/39 (0%) | 0/39 (0%) | ||||||||
| Vessel puncture site pain | 0/39 (0%) | 0/39 (0%) | 0/39 (0%) | 0/38 (0%) | 0/40 (0%) | 2/38 (5.3%) | 0/39 (0%) | 0/39 (0%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Upper respiratory tract infection | 0/39 (0%) | 2/39 (5.1%) | 1/39 (2.6%) | 0/38 (0%) | 1/40 (2.5%) | 0/38 (0%) | 0/39 (0%) | 1/39 (2.6%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Back pain | 3/39 (7.7%) | 1/39 (2.6%) | 0/39 (0%) | 1/38 (2.6%) | 2/40 (5%) | 1/38 (2.6%) | 2/39 (5.1%) | 0/39 (0%) | ||||||||
| Arthralgia | 0/39 (0%) | 0/39 (0%) | 2/39 (5.1%) | 0/38 (0%) | 0/40 (0%) | 1/38 (2.6%) | 0/39 (0%) | 1/39 (2.6%) | ||||||||
| Myalgia | 1/39 (2.6%) | 0/39 (0%) | 1/39 (2.6%) | 0/38 (0%) | 0/40 (0%) | 0/38 (0%) | 1/39 (2.6%) | 2/39 (5.1%) | ||||||||
| Pain in extremity | 1/39 (2.6%) | 0/39 (0%) | 0/39 (0%) | 1/38 (2.6%) | 1/40 (2.5%) | 0/38 (0%) | 0/39 (0%) | 4/39 (10.3%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Headache | 3/39 (7.7%) | 4/39 (10.3%) | 5/39 (12.8%) | 7/38 (18.4%) | 2/40 (5%) | 6/38 (15.8%) | 6/39 (15.4%) | 4/39 (10.3%) | ||||||||
| Dizziness | 1/39 (2.6%) | 1/39 (2.6%) | 0/39 (0%) | 3/38 (7.9%) | 1/40 (2.5%) | 0/38 (0%) | 2/39 (5.1%) | 2/39 (5.1%) | ||||||||
| Somnolence | 1/39 (2.6%) | 1/39 (2.6%) | 2/39 (5.1%) | 1/38 (2.6%) | 1/40 (2.5%) | 2/38 (5.3%) | 0/39 (0%) | 0/39 (0%) | ||||||||
| Psychiatric disorders | ||||||||||||||||
| Anxiety | 1/39 (2.6%) | 0/39 (0%) | 1/39 (2.6%) | 1/38 (2.6%) | 0/40 (0%) | 0/38 (0%) | 0/39 (0%) | 2/39 (5.1%) | ||||||||
| Reproductive system and breast disorders | ||||||||||||||||
| Menorrhagia | 0/39 (0%) | 0/39 (0%) | 0/39 (0%) | 1/38 (2.6%) | 1/40 (2.5%) | 0/38 (0%) | 2/39 (5.1%) | 0/39 (0%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Epistaxis | 1/39 (2.6%) | 0/39 (0%) | 2/39 (5.1%) | 1/38 (2.6%) | 2/40 (5%) | 0/38 (0%) | 3/39 (7.7%) | 2/39 (5.1%) | ||||||||
| Oropharyngeal pain | 1/39 (2.6%) | 1/39 (2.6%) | 0/39 (0%) | 2/38 (5.3%) | 0/40 (0%) | 0/38 (0%) | 1/39 (2.6%) | 0/39 (0%) | ||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Ecchymosis | 3/39 (7.7%) | 1/39 (2.6%) | 3/39 (7.7%) | 3/38 (7.9%) | 4/40 (10%) | 2/38 (5.3%) | 2/39 (5.1%) | 0/39 (0%) | ||||||||
| Pruritus generalized | 2/39 (5.1%) | 1/39 (2.6%) | 0/39 (0%) | 1/38 (2.6%) | 1/40 (2.5%) | 1/38 (2.6%) | 2/39 (5.1%) | 1/39 (2.6%) | ||||||||
| Acne | 0/39 (0%) | 1/39 (2.6%) | 1/39 (2.6%) | 2/38 (5.3%) | 0/40 (0%) | 0/38 (0%) | 1/39 (2.6%) | 1/39 (2.6%) | ||||||||
| Pruritus | 1/39 (2.6%) | 0/39 (0%) | 4/39 (10.3%) | 0/38 (0%) | 1/40 (2.5%) | 0/38 (0%) | 1/39 (2.6%) | 0/39 (0%) | ||||||||
| Rash papular | 1/39 (2.6%) | 1/39 (2.6%) | 2/39 (5.1%) | 0/38 (0%) | 0/40 (0%) | 0/38 (0%) | 0/39 (0%) | 0/39 (0%) | ||||||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights therefrom or any data, information or materials obtained or generated in the performance of it's obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
Results Point of Contact
| Name/Title | Sr. VP, Clinical Science |
|---|---|
| Organization | Takeda Global Research and Development Center, Inc. |
| Phone | 800-778-2860 |
| clinicaltrialregistry@tpna.com |
- TAK-390MR_101
- U1111-1112-6792