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A Phase 1, Randomized, Open-Label, Crossover Study to Evaluate the Bioequivalence of Single Oral Dose of TAK-438ASA tablet and Single Oral Dose of TAK-438 tablet plus Aspirin Enteric-Coated tablet (Study 1) and the Food Effect of Single Oral Dose of TAK-438ASA tablet (Study 2) in Healthy Adult Male Subjects

A Study to Evaluate the Bioequivalence and the Food Effect of TAK-438ASA tablet

276

No significant differences were observed between the sequences, or between the safety analysis set and the PK analysis set in each study.

Study 1: BE Study Pilot study A total of 24 participants were enrolled in the pilot BE study (Study 1) that consisted of sequences a and b (12 participants each). The participants assigned to sequence a received a single dose of TAK-438ASA tablet containing TAK-438 10 mg and aspirin 100 mg (fixed dose combination) followed by a single dose of TAK-438 tablet 10 mg and aspirin enteric-coated tablet 100 mg (free combination), whereas the participants assigned to sequence b received a single dose of free combination followed by a single dose of fixed dose combination. Of these, 23 participants completed the study and 1 participant in sequence a prematurely discontinued the study because of "AE." Pivotal study A total of 240 participants were enrolled in the pivotal BE study (Study 1) that also consisted of sequences a and b (120 participants each). The participants assigned to each sequence received the study drug under the same dosing conditions as those of the pilot BE study. Of these, 236 participants completed the study and 4 participants (1 in sequence a and 3 in sequence b) prematurely discontinued the study. The reasons for the premature discontinuation were "withdrawal by participant" in 3 participants (1 in sequence a and 2 in sequence b) and "AE" in 1 participant in sequence b. Study 2: food effect study A total of 12 participants were enrolled in the food effect study (Study 2) that consisted of sequences c and d (6 participants each). The participants assigned to sequence c received a single dose of TAK-438ASA tablet under fasted (without breakfast) condition, whereas the participants assigned to sequence d received a single dose of TAK-438ASA tablet under fed (30 minutes after starting breakfast) condition. All the participants completed the food effect study (Study 2).

In the pilot BE study (Study 1) and the food effect study (Study 2), upper respiratory tract infection was reported in 1 participant (4.2%) who received fixed dose combination in the pilot BE study (Study 1), and 1 participant (8.3%) who received fixed dose combination under fasted condition in the food effect study (Study 2). All TEAEs were mild in intensity, and no TEAEs of special interest were reported. In the pivotal BE study (Study 1), pharyngitis was reported in 6 participants (2.5%) who received fixed dose combination and 2 participants (0.8%) who received free combination. Nasopharyngitis was reported in 2 participants (0.8%) who received fixed dose combination, and liver function test abnormal was reported in 1 participant (0.4%) who received free combination. Of these, pharyngitis reported in 5 participants (2.1%) who received fixed dose combination and 1 participant (0.4%) who received free combination was moderate in intensity, while remaining TEAEs were mild in intensity. As for TEAE of special interest, liver function test abnormal was reported in 1 participant (0.4%) who received free combination, which was mild in intensity and considered not related to the study drug. All TEAEs were considered not related to the study drug. No deaths, serious TEAEs, or TEAEs leading to study drug discontinuation were reported during the study. Except for the 1 event of liver function test abnormal reported as a TEAE of special interest and 1 event of clinically significant abnormality in ECG associated with the TEAE of pharyngitis, there were no clinically significant changes or findings in clinical laboratory tests, vital signs, body weight, or ECGs.

Study 1: BE Study Pilot study The ANOVA results showed that the point estimates of the differences (fixed dose combination - free combination) [90% CIs] in natural log-transformed AUClast and Cmax of TAK-438F were ln(1.006) [ln(0.967) - ln(1.047)] and ln(1.052) [ln(0.992) - ln(1.116)], respectively. Those of unchanged aspirin were ln(1.056) [ln(0.910) - ln(1.226)] and ln(1.096) [ln(0.875) - ln(1.372)], respectively. The two-sided 90% CIs of the differences (fixed dose combination - free combination) in natural log-transformed Cmax of unchanged aspirin failed to fall in the BE range, ie, between ln(0.80) and ln(1.25), while the two-sided 90% CIs of the differences in natural log-transformed Cmax of TAK-438F and AUClast of both TAK-438F and unchanged aspirin fell in the BE range. The point estimates of the differences (fixed dose combination - free combination) in natural log-transformed AUClast and Cmax of both TAK-438F and unchanged aspirin fell in the range between ln(0.90) and ln(1.11). However, the dissolution test did not demonstrate the similarity between a fixed dose combination and a free combination with regard to aspirin (Report of Test Result. Bioequivalence Study of TAK-438ASA Tablet [10 mg + 100 mg] - Dissolution Test. 07 August 2018). The point estimates of the differences (fixed dose combination - free combination) [90% CIs] in natural log-transformed AUC(infinity), tmax, MRT (infinity,ev), and Lambda (z) of TAK-438F were ln(1.010) [ln(0.971) - ln(1.051)], ln(0.972) [ln(0.847) - ln(1.116)], ln(0.985) [ln(0.956) - ln(1.015)], and ln(0.981) [ln(0.935) - ln(1.029)], respectively. Those of unchanged aspirin were ln(1.056) [ln(0.911) - ln(1.225)], ln(0.864) [ln(0.781) - ln(0.957)], ln(0.888) [ln(0.804) - ln(0.980)], and ln(1.015) [ln(0.929) - ln(1.108)], respectively. Thus, the pilot study demonstrated the BE of a single-dose TAK-438ASA tablet (given as a fixed dose combination) to concomitant administration of a single-dose TAK-438 tablet and aspirin enteric-coated tablet (given as a free combination) for TAK-438F. However, the study results were not decisive about the BE for unchanged aspirin. Pivotal study The BE analysis was performed only for unchanged aspirin in the pivotal study. The ANOVA results showed that the point estimates of the differences (fixed dose combination - free combination) [90% CIs] in natural log-transformed AUClast, and Cmax of unchanged aspirin were ln(1.095) [ln(1.041) - ln(1.153)] and ln(1.258) [ln(1.164) - ln(1.359)], respectively. The Cmax of unchanged aspirin showed higher tendency for fixed dose combination than that for free combination. The two-sided 90% CIs of the differences (fixed dose combination - free combination) in natural log-transformed Cmax of unchanged aspirin failed to fall in the BE range, ie, between ln(0.80) and ln(1.25), while that of AUClast fell in the BE range. The point estimates of the differences (fixed dose combination - free combination) in natural log-transformed Cmax of unchanged aspirin also failed to fall in the range between ln(0.90) and ln(1.11), while that of AUClast fell in the range. The point estimates of the differences (fixed dose combination - free combination) [90% CIs] in natural log-transformed AUC(infinity), tmax, MRT(infinity, ev), and Lambda(z) of unchanged aspirin were ln(1.068) [ln(1.014) - ln(1.124)], ln(0.846) [ln(0.812) - ln(0.881)], ln(0.872) [ln(0.841) - ln(0.905)], and ln(0.998) [ln(0.955) - ln(1.043)], respectively. Thus, the results of the pivotal study were not decisive about the BE of a single-dose TAK-438ASA tablet (given as a fixed dose combination) to concomitant administration of TAK-438 tablet and aspirin enteric-coated tablet (given as a free combination) for unchanged aspirin. Study 2: food effect study The ANOVA results of TAK-438F showed that the point estimates of the differences (fed condition - fasted condition) [90% CIs] in natural log-transformed AUC(infinity), AUC48, AUClast, and Cmax were ln(1.238) [ln(1.175) - ln(1.306)], ln(1.241) [ln(1.180) - ln(1.306)], ln(1.245) [ln(1.182) - ln(1.311)], and ln(1.441) [ln(1.244) - ln(1.670)], respectively. Although the Cmax of TAK-438F showed higher tendency under fed condition than under fasted condition, AUC(infinity), AUC48, and AUClast were similar between these conditions. Thus, the food effect on PK of TAK-438 following administration of TAK-438ASA tablet was not considered to be clinically significant. The ANOVA results of unchanged aspirin showed that the point estimates of the differences (fed condition - fasted condition) [90% CIs] in natural log-transformed AUC(infinity), AUC24, AUClast, and Cmax were ln(1.232) [ln(0.994) - ln(1.528)], ln(1.234) [ln(0.995) - ln(1.529)], ln(1.233) [ln(0.995) - ln(1.529)], and ln(1.500) [ln(1.084) - ln(2.078)], respectively. The ANOVA results of salicylic acid showed that the point estimates of the differences (fed condition - fasted condition) [90% CIs] in natural log-transformed AUC(infinity), AUC24, AUClast, and Cmax were ln(1.014) [ln(0.938) - ln(1.096)], ln(1.014) [ln(0.931) - ln(1.104)], ln(1.020) [ln(0.933) - ln(1.115)], and ln(1.218) [ln(1.112) - ln(1.333)], respectively. Although the Cmax of aspirin showed higher tendency under fed condition than under fasted condition, AUC(infinity), AUC24, and AUClast were similar between these conditions. Cmax, AUC(infinity), AUC24, and AUClast of salicylic acid were similar between fed and fasted conditions. Thus, the food effect on PK of aspirin following administration of TAK-438ASA tablet was not considered to be clinically significant. Conclusions: The pilot BE study (Study 1) demonstrated the BE of a single-dose TAK-438ASA tablet (given as a fixed dose combination) to concomitant administration of a single-dose TAK-438 tablet and aspirin enteric-coated tablet (given as a free combination) except with regard to Cmax of unchanged aspirin. The pivotal BE study (Study 1) did not fully demonstrate the BE of a single-dose TAK-438ASA tablet to concomitant administration of a single-dose TAK-438 tablet and aspirin enteric-coated tablet with regard to Cmax of unchanged aspirin. The food effect on PK following administration of TAK-438ASA tablet was not considered to be clinically significant. A single dose of TAK-438ASA tablet was well tolerated with no clinically significant concerns for safety in Japanese healthy adult male participants.

Please refer to "Primary Outcome Measures" section.

Please refer to "Primary Outcome Measures" section.

Yes

Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Takeda Pharmaceutical Company Limited

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Takeda Pharmaceutical Company Limited

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completed

Mar. 08, 2018

Interventional

Randomized, Open-Label, 2x2 Crossover

treatment purpose

1

1. In the opinion of the investigator or sub-investigator, participants are capable of understanding the procedures required for the study and complying with its requirements
2. Participants sign and date an informed consent form by themselves prior to the initiation of any study procedures
3. Japanese healthy men aged >= 20 and =< 60, inclusive, at the time of consent
4. Body weight >= 50 kg as well as body mass index (BMI) >= 18.5 kg/m^2 and =< 25.0 kg/m^2 at screening test

1. Participants who received study drug within 16 weeks (112 days) prior to the start of study treatment in Period 1
2. Participants who received TAK-438 or aspirin in a previous study
3. Staffs at the study site and their family, or participants who depend on the study-related staffs at the study site (e.g., husband and wife, parents, children, brothers and sisters), or participants who may be constrained to consent to the study
4. Participants with uncontrolled and clinically significant neurological, cardiovascular, lung, hepatic, renal, metabolic, gastrointestinal, urinary or endocrine disease, or other abnormalities (except for diseases investigated) that might affect the study participation or impact the results of the study
5. Participants with a previous or current history of aspirin asthma (asthmatic attack induced by non-steroidal anti-inflammatory drugs, etc.)
6. Participants with hypersensitivity for components of TAK-438 tablet or aspirin enteric-coated tablet, or salicylic acid-based products
7. Positive result in urinary test for illegal drug abuse at screening
8. Participants who have a history of illegal drug abuse or alcoholism within the past 2 years prior to the screening visit, or who are not willing to refrain from alcohol consumption and drug use during the study period
9. Participants who ingested a medicine, a supplement or food forbidden to be used in combination during the specified time period.
10. Participants with a current history or recent episodes (within the past 6 months) of gastrointestinal diseases (malabsorption, gastroesophageal reflux, peptic ulcer disease, erosive oesophagitis), frequent (at least once per week) heartburn or surgical intervention that might affect drug absorption
11. Participants with a history of cancer, except for basal cell carcinoma in remission for >= 5 years prior to Day 1
12. Positive results at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen, or serological test for syphilis
13. Participants who have difficulties in blood draw from peripheral veins
14. Participants who had >= 200 mL of whole blood drawn within 4 weeks (28 days) prior to the start of study treatment in Period 1 or who had >= 400 mL of whole blood drawn within 12 weeks (84 days) prior to the start of study treatment in Period 1
15. Participants who had a total of >= 800 mL of whole blood drawn within 52 weeks (364 days) prior to the start of study treatment in Period 1
16. Participants who had blood components drawn within 2 weeks (14 days) prior to the start of study treatment in Period 1
17. Clinically significant abnormalities in electrocardiogram at screening or admission (Day -1)
18. Participants with abnormal laboratory parameters suggestive of clinically significant underlying diseases or who have abnormal values in the following measures at screening: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) over the upper limit of normal
19. Participants who are unlikely to comply with the protocol or deemed ineligible due to other reasons by the principal investigator or other investigators.

Male

Healthy Volunteers

investigational material(s)
Generic name etc : TAK-438ASA, TAK-438, Aspirin
INN of investigational material : Vonoprazan, acetylsalicylic acid
Therapeutic category code : 339 Other agents relating to blood and body fluides
Dosage and Administration for Investigational material : Pilot phase of Study 1, TAK-438ASA + TAK-438 and Aspirin: One TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 1 in the Pilot phase of Study 1 (Day 1), followed by a washout period (Days 2 to 15), followed by one TAK-438 10 mg tablet and one aspirin 100 mg tablet, orally without breakfast, on Day 1 of Period 2 in the Pilot phase of Study 1 (Day 16).
Generic name etc : TAK-438ASA, TAK-438, Aspirin
INN of investigational material : Vonoprazan, acetylsalicylic acid
Therapeutic category code : 339 Other agents relating to blood and body fluides
Dosage and Administration for Investigational material : Pilot phase of Study 1, TAK-438 and Aspirin + TAK-438ASA: One TAK-438 10 mg tablet and one aspirin 100 mg tablet, orally without breakfast, on Day 1 of Period 1 in the Pilot phase of Study 1 (Day 1), followed by a washout period (Days 2 to 15), followed by, one TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 2 in the Pilot phase of Study 1 (Day 16).
Generic name etc : TAK-438ASA, TAK-438, Aspirin
INN of investigational material : Vonoprazan, acetylsalicylic acid
Therapeutic category code : 339 Other agents relating to blood and body fluides
Dosage and Administration for Investigational material : Pivotal phase of Study 1, TAK-438ASA + TAK-438 and Aspirin: One TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 1 in the Pivotal phase of Study 1 (Day 1), followed by a washout period (Days 2 to 15), followed by one TAK-438 10 mg tablet and one aspirin 100 mg tablet, orally without breakfast, on Day 1 of Period 2 in the Pivotal phase of Study 1 (Day 16).
Generic name etc : TAK-438ASA, TAK-438, Aspirin
INN of investigational material : Vonoprazan, acetylsalicylic acid
Therapeutic category code : 339 Other agents relating to blood and body fluides
Dosage and Administration for Investigational material : Pivotal phase of Study 1, TAK-438 and Aspirin + TAK-438ASA: One TAK-438 10 mg tablet and one aspirin 100 mg tablet, orally without breakfast, on Day 1 of Period 1 in the Pivotal phase of Study 1 (Day 1), followed by a washout period (Days 2 to 15), followed by, one TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 2 in the Pivotal phase of Study 1 (Day 16).
Generic name etc : TAK-438ASA
INN of investigational material : -
Therapeutic category code : 339 Other agents relating to blood and body fluides
Dosage and Administration for Investigational material : Study 2, TAK-438ASA (Fasted + Fed condition): One TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 1 in Study 2 (Day 1), followed by a washout period (Days 2 to 15), followed by one TAK-438ASA tablet, orally 30 minutes after breakfast, on Day 1 of Period 2 in Study 2 (Day 16).
Generic name etc : TAK-438ASA
INN of investigational material : -
Therapeutic category code : 339 Other agents relating to blood and body fluides
Dosage and Administration for Investigational material : Study 2, TAK-438ASA (Fed + Fasted condition): One TAK-438ASA tablet, orally 30 minutes after breakfast, on Day 1 of Period 1 in Study 2 (Day 1), followed by a washout period (Days 2 to 15), followed by one TAK-438ASA tablet, orally without breakfast, on Day 1 of Period 2 in Study 2 (Day 16).

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

pharmacokinetics
Study 1, AUClast: Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Free Base of TAK-438 (TAK-438-F)
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 1, Cmax: Maximum Observed Plasma Concentration for TAK-438F
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 1, AUClast: Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin
Time Frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose

pharmacokinetics
Study 1, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin
Time Frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose

pharmacokinetics
Study 1, AUC(infinity): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-438F
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 1, MRT(infinity, ev): Mean Residence Time from Time 0 to Infinity for TAK-438F
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for TAK-438F
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 1, AUC(infinity): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Unchanged Aspirin
Time Frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose

pharmacokinetics
Study 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin
Time Frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose

pharmacokinetics
Study 1, MRT(infinity, ev): Mean Residence Time from Time 0 to Infinity for Unchanged Aspirin
Time Frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose

pharmacokinetics
Study 1, Lambda (z): Terminal Disposition Phase Rate Constant for Unchanged Aspirin
Time Frame: Day 1 pre-dose and at multiple time points (up to 12 hours) post-dose

pharmacokinetics
Study 2, AUC(infinity): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-438F and its Metabolites (M) (M-I, M-II, M-III and M-IV-Sul)
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 2, AUC(0-48): Area Under the Plasma Concentration-time Curve from Time 0 to Time 48 Hours Over the Dosing Interval for TAK-438F and its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 2, AUClast: Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for TAK-438F and its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 2, Cmax: Maximum Observed Plasma Concentration for TAK-438F and its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-438F and its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 2, T1/2z: Terminal Disposition Phase Half-life for TAK-438F and its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 2, AUC(infinity): Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Unchanged Aspirin and its Metabolite (Salicylic Acid)
Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose

pharmacokinetics
Study 2, AUC(0-24): Area Under the Plasma Concentration-time Curve from Time 0 to Time 24 Hours Over the Dosing Interval for Unchanged Aspirin and its Metabolite (Salicylic Acid)
Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose

pharmacokinetics
Study 2, AUClast: Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Unchanged Aspirin and its Metabolite (Salicylic Acid)
Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose

pharmacokinetics
Study 2, Cmax: Maximum Observed Plasma Concentration for Unchanged Aspirin and its Metabolite (Salicylic Acid)
Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose

pharmacokinetics
Study 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Unchanged Aspirin and its Metabolite (Salicylic Acid)
Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose

pharmacokinetics
Study 2, T1/2z: Terminal Disposition Phase Half-life for Unchanged Aspirin and its Metabolite (Salicylic Acid)
Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose

pharmacokinetics
Study 2, Ae(0-48): Amount of Drug Excreted in Urine from Time 0 to 48 Hours for TAK-438F and its Metabolites (M-I, M-II, M-III, and M-IV-Sul)
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 2, Fe(0-48): Fraction of Administered Dose Excreted into Urine from Time 0 to Time 48 Hours for TAK-438F and its Metabolites (M-I, M-II, M-III and M-IV-Sul)
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 2, CLR: Renal Clearance for TAK-438F and its Metabolites (M-I, M-II, M-III, and M-IV-Sul)
Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose

pharmacokinetics
Study 2, Ae(0-24): Amount of Drug Excreted in Urine from Time 0 to 24 Hours for Unchanged Aspirin and its Metabolites (Salicylic Acid and Salicyluric Acid)
Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose

pharmacokinetics
Study 2, Fe(0-24): Fraction of Administered Dose Excreted into Urine from Time 0 to Time 24 Hours for Unchanged Aspirin and its Metabolites (Salicylic Acid and Salicyluric Acid)
Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose

pharmacokinetics
Study 2, CLR: Renal Clearance for Unchanged Aspirin and its Metabolites (Salicylic Acid and Salicyluric Acid)
Time Frame: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose

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Mar. 05, 2018