A Phase 1, Bioequivalence Study of SYR-472 25mg and 50mg Tablets

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02372097
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 23.6

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the bioequivalence of 2 tablets of SYR-472 25 milligram (mg) and 1 tablet of SYR-472 50 mg administered to healthy adult males.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: SYR-472	Phase 1

Detailed Description

Bioequivalence of 2 SYR-472 25 mg tablets and 1 SYR-472 50 mg tablet administered to healthy adult males will be investigated in a randomized, open-label, crossover study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Crossover Phase 1 Study to Evaluate the Bioequivalence Following a Single Oral Dose Administration of SYR-472 25mg and 50mg Tablets in Healthy Adult Male Subjects
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Participants in group A will be orally administered 2 tablets of SYR-472 25 mg in period 1 and 1 tablet of SYR-472 50 mg tablet in period 2, both in a single dose under fasting conditions in the morning.	Drug: SYR-472; SYR-472 25mg, 50mg
Experimental: Group B Participants in group B will be orally administered 1 tablet of SYR-472 50 mg in period 1 and 2 tablets of SYR-472 25 mg tablets in period 2, both in a single dose under fasting conditions in the morning.	Drug: SYR-472; SYR-472 25mg, 50mg

Outcome Measures

Primary Outcome Measures

1. AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Unchanged SYR-472 (SYR-472Z) [Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period]

2. Cmax: Maximum Observed Plasma Concentration for SYR-472Z [Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period]

Secondary Outcome Measures

1. AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for SYR-472Z [Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period]

2. Tmax: Time to Reach the Cmax for SYR-472Z [Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period]

3. MRT: Mean Residence Time From Time Zero to Infinity for SYR-472Z [Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period]

4. Apparent Terminal Elimination Rate Constant (λz) for SYR-472Z [Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period]

5. Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs) [Day 1 of Period 1 up to the day of hospital discharge (Day 29) in Period 2]

   Collection of AEs commenced from the time that the participant was first administered study drug in Period 1 (Day 1). Routine collection of AEs continued until the end (hospital discharge) of Period 2 (Day 29).

6. Number of Participants With TEAEs Related to Vital Signs [Day 1 of Period 1 up to the day of hospital discharge (Day 29) in Period 2]

7. Number of Participants With TEAEs Related to Body Weight [Day 1 of Period 1 up to the day of hospital discharge (Day 29) in Period 2]

8. Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values [Day 1 of Period 1 up to the day of hospital discharge (Day 29) in Period 2]

9. Number of Participants Who Had Abnormal and Clinically Significant 12-lead Electrocardiograms (ECG) Findings After Study Drug Administration [Baseline up to 7 days after the last dose of study drug (Day 8) in each period]

   Participants whose results of electrocardiograms were judged as abnormal and clinically significant by investigator after study drug administration were counted in this measure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 35 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Participants who understand the outline of the clinical study and are capable of complying with their responsibilities as participants, as judged by the investigator or sub investigator.

2. Participants who can sign and date the informed consent form before the initiation of the study procedure.

3. Healthy Japanese adult males.

4. Participants who are 20 to 35 years of age at the time of informed consent.

5. Participants who weigh 50.0 kilogram (kg) or more with a body mass index (BMI) of 18.5 to less than 25.0 kilogram per square meter (kg/m^2) in the screening period.

Exclusion Criteria:

1. Participants who were administered any investigational product within 16 weeks (112 days) before the start of the study drug administration in stage 1.

2. Participants who have received SYR-472 in the past.

3. Employees of the study site, their family members, those who are in a dependency relationship with employees of the study site involved in the conduct of the study (for example [e.g.], spouse, parents, children, brothers and sisters), and those who might be coerced to consent to participate in the study.

4. Participants who have poorly controlled, clinically significant abnormalities of the nervous system, cardiovascular system, lung, liver, kidneys, metabolism, gastrointestinal system, urinary system, or endocrinological system, which possibly may affect study participation or study results.

5. Participants who have a positive urine drug test in the screening period.

6. Participants who need to use drugs or foods listed in the table of prohibited concomitant drugs and foods.

7. Participants who have a history of hypersensitivity or allergy to drugs (including SYR-472 and its ingredients).

8. Participants who currently have or recently had (within the past 6 months) gastrointestinal disease that may affect drug absorption (malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [at least once a week] heartburn, surgical intervention [e.g., cholecystectomy]).

9. Participants with a past history of cancer.

10. Participants who are positive for any of the following during the screening period: hepatitis B virus surface antigen (HBsAg), antibody against hepatitis C virus (HCV), human immunodeficiency virus (HIV) antigen, anti-HIV antibody, or serological test for syphilis.

11. Participants with difficulty having blood collected from a peripheral vein.

12. Participants who donated 200 milliliter (mL) or more of whole blood within the 4 weeks (28 days) or 400 mL or more of whole blood within the 12 weeks (84 days) before starting the study drug administration in stage 1.

13. Participants who donated a total of 800 mL or more of whole blood within the 52 weeks (364 days) before starting the study drug administration in stage 1.

14. Participants who donated blood components within the 2 weeks (14 days) before starting the study drug administration in stage 1.

15. Participants who show clinically significant abnormalities in electrocardiogram (ECG) during the screening period or on Day 1 (before the study drug administration).

16. Participants who have laboratory test abnormalities suggestive of a clinically significant primary disease or who have abnormal values in any of the following parameters: alanine aminotransferase (ALT) or aspartate serum transaminase AST exceeding 1.5 times the upper limit of the normal range.

17. Participants who are unlikely to comply with the study protocol or are ineligible for the study for any other reason, as judged by the investigator or sub investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Fukuoka		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02372097
• Other Study ID Numbers: SYR-472-1005; U1111-1167-0746; JapicCTI-152813; JapicCTI-R160849
• First Posted: Feb 26, 2015
• Last Update Posted: May 13, 2016
• Last Verified: Apr 1, 2016

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in Japan from 04 March 2015 to 08 April 2015.
Pre-assignment Detail	Healthy male participants were enrolled in 1 of the 2 treatment sequences in either Period 1 or 2: Group A: 25 milligram (mg) tablet in Period 1 followed by 50 mg tablet in Period 2, Group B: 50 mg tablet in Period 1 followed by 25 mg tablet in Period 2.

Arm/Group Title	SYR-472 25 mg + SYR-472 50 mg	SYR-472 50 mg + SYR-472 25 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, orally, on Day 1 of the first intervention period (8 days), followed by at least 13 days washout period, followed by SYR-472 50 mg, tablet, orally on Day 1 of the second intervention period (8 days).	SYR-472 50 mg, 1 tablet, orally, on Day 1 of the first intervention period (8 days), followed by at least 13 days washout period, followed by SYR-472 25 mg, 2 tablets, orally on Day 1 of the second intervention period (8 days).
Period Title: First Intervention Period (8 Days)
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: First Intervention Period (8 Days)
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: First Intervention Period (8 Days)
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	SYR-472 25 mg + SYR-472 50 mg	SYR-472 50 mg + SYR-472 25 mg	Total
Arm/Group Description	SYR-472 25 mg, 2 tablets, orally, on Day 1 of the first intervention period (8 days), followed by at least 13 days washout period, followed by SYR-472 50 mg, tablet, orally on Day 1 of the second intervention period (8 days).	SYR-472 50 mg, 1 tablet, orally, on Day 1 of the first intervention period (8 days), followed by at least 13 days washout period, followed by SYR-472 25 mg, 2 tablets, orally on Day 1 of the second intervention period (8 days).	Total of all reporting groups
Overall Participants	12	12	24
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	23.7 (2.64)	22.3 (3.17)	23.0 (2.93)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	12 100%	12 100%	24 100%
Region of Enrollment (participants) [Number]
Japan	12 100%	12 100%	24 100%
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	172.0 (6.93)	172.8 (7.48)	172.4 (7.06)
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	64.51 (9.707)	62.79 (6.087)	63.65 (7.972)
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	21.69 (1.866)	21.05 (1.948)	21.37 (1.894)
Smoking Classification (participants) [Number]
Never Smoked	7 58.3%	7 58.3%	14 58.3%
Current Smoker	5 41.7%	4 33.3%	9 37.5%
Ex-Smoker	0 0%	1 8.3%	1 4.2%
Alcohol Classification (participants) [Number]
Drinks a Few Days per Week	2 16.7%	5 41.7%	7 29.2%
Drinks a Few Days per Month	7 58.3%	4 33.3%	11 45.8%
Never Drunk	3 25%	3 25%	6 25%
Caffeine Classification (participants) [Number]
Caffeine Consumer	4 33.3%	2 16.7%	6 25%
Caffeine Non-Consumer	8 66.7%	10 83.3%	18 75%

Outcome Measures

1. Primary Outcome

Title	AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Unchanged SYR-472 (SYR-472Z)
Time Frame	Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period

Outcome Measure Data

Analysis Population Description

The PK analysis set included all participants who received study drug, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for PK.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Geometric Mean (Standard Deviation) [nanogram hour per milliliter(ng*hr/mL)]	2733 (445.48)	2780 (437.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SYR-472 25 mg, SYR-472 50 mg
	Comments	The 2-sided 90% confidence interval for the difference between the products (2 tablets of SYR-472 25 mg, 1 tablet of SYR-472 50 mg) was determined from the ANOVA model with the natural logarithms of the AUC(0-168) as a dependent variable, and product, group and period as fixed effects.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Two tablets of SYR-472 25 mg and 1 tablet of SYR-472 50 mg were considered bioequivalent if 90% CI of the mean differences of natural log-transformed AUC(0-168) of SYR-472Z was within the range of ln(0.80) to ln(1.25) or within the range of ln(0.9) to ln(1.11) and the results of dissolution test satisfied the requirement.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least square (LS) mean difference
	Estimated Value	-0.0170
	Confidence Interval	(2-Sided) 90%; -0.0344 to 0.0004
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for SYR-472Z
Time Frame	Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period

Outcome Measure Data

Analysis Population Description

The PK analysis set included all participants who received study drug, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for PK.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Geometric Mean (Standard Deviation) [nanogram per milliliter(ng/mL)]	196.5 (54.034)	223.6 (67.200)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SYR-472 25 mg, SYR-472 50 mg
	Comments	The 2-sided 90% confidence interval for the difference between the products (2 tablets of SYR-472 25 mg, 1 tablet of SYR-472 50 mg) was determined from the ANOVA model with the natural logarithms of the Cmax as a dependent variable, and product, group and period as fixed effects.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Two tablets of SYR-472 25 mg and 1 tablet of SYR-472 50 mg were considered bioequivalent if 90% CI of the mean differences of natural log-transformed Cmax of SYR-472Z was within the range of ln(0.80) to ln(1.25) or within the range of ln(0.9) to ln(1.11) and the results of dissolution test satisfied the requirement.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.1292
	Confidence Interval	(2-Sided) 90%; -0.2177 to -0.0406
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity for SYR-472Z
Time Frame	Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period

Outcome Measure Data

Analysis Population Description

The PK analysis set included all participants who received study drug, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for PK.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Geometric Mean (Standard Deviation) [ng*hr/mL]	2829 (466.32)	2889 (454.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SYR-472 25 mg, SYR-472 50 mg
	Comments	The 2-sided 90% confidence interval for the difference between the products (2 tablets of SYR-472 25 mg, 1 tablet of SYR-472 50 mg) was determined from the ANOVA model with the natural logarithms of the AUC(0-inf) as a dependent variable, and product, group and period as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.0210
	Confidence Interval	() 90%; -0.0362 to -0.0058
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Tmax: Time to Reach the Cmax for SYR-472Z
Time Frame	Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period

Outcome Measure Data

Analysis Population Description

The PK analysis set included all participants who received study drug, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for PK.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Median (Full Range) [hour(hr)]	1.5000 (1.2682)	1.000 (1.1227)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SYR-472 25 mg, SYR-472 50 mg
	Comments	The 2-sided 90% confidence interval for the difference between the products (2 tablets of SYR-472 25 mg, 1 tablet of SYR-472 50 mg) was determined from the ANOVA model with Tmax as a dependent variable, and product, group and period as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.3750
	Confidence Interval	(2-Sided) 90%; -0.1452 to 0.8952
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	MRT: Mean Residence Time From Time Zero to Infinity for SYR-472Z
Time Frame	Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period

Outcome Measure Data

Analysis Population Description

The PK analysis set included all participants who received study drug, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for PK.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Geometric Mean (Standard Deviation) [hr]	32.52 (4.7575)	33.07 (4.8613)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SYR-472 25 mg, SYR-472 50 mg
	Comments	The 2-sided 90% confidence interval for the difference between the products (2 tablets of SYR-472 25 mg, 1 tablet of SYR-472 50 mg) was determined from the ANOVA model with the natural logarithms of the MRT as a dependent variable, and product, group and period as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.0168
	Confidence Interval	(2-Sided) 90%; -0.0504 to 0.0169
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Apparent Terminal Elimination Rate Constant (λz) for SYR-472Z
Time Frame	Day 1: pre dose (within 3 hours prior to dosing), and at multiple time points (up to 168 hours) post dose in each period

Outcome Measure Data

Analysis Population Description

The PK analysis set included all participants who received study drug, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for PK.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Geometric Mean (Standard Deviation) [per hour(hr-1)]	0.01399 (0.0036008)	0.01254 (0.0028378)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SYR-472 25 mg, SYR-472 50 mg
	Comments	The 2-sided 90% confidence interval for the difference between the products (2 tablets of SYR-472 25 mg, 1 tablet of SYR-472 50 mg) was determined from the ANOVA model with the natural logarithms of the λz as a dependent variable, and product, group and period as fixed effects.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.1099
	Confidence Interval	(2-Sided) 90%; 0.0235 to 0.1963
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs)
Description	Collection of AEs commenced from the time that the participant was first administered study drug in Period 1 (Day 1). Routine collection of AEs continued until the end (hospital discharge) of Period 2 (Day 29).
Time Frame	Day 1 of Period 1 up to the day of hospital discharge (Day 29) in Period 2

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received study drug.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Number [participants]	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants With TEAEs Related to Vital Signs
Time Frame	Day 1 of Period 1 up to the day of hospital discharge (Day 29) in Period 2

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received study drug.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Number [participants]	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants With TEAEs Related to Body Weight
Time Frame	Day 1 of Period 1 up to the day of hospital discharge (Day 29) in Period 2

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received study drug.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Number [participants]	0 0%	0 0%

10. Secondary Outcome

Title	Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Laboratory Values
Time Frame	Day 1 of Period 1 up to the day of hospital discharge (Day 29) in Period 2

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received study drug.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Number [participants]	0 0%	0 0%

11. Secondary Outcome

Title	Number of Participants Who Had Abnormal and Clinically Significant 12-lead Electrocardiograms (ECG) Findings After Study Drug Administration
Description	Participants whose results of electrocardiograms were judged as abnormal and clinically significant by investigator after study drug administration were counted in this measure.
Time Frame	Baseline up to 7 days after the last dose of study drug (Day 8) in each period

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received study drug.

Arm/Group Title	SYR-472 25 mg	SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.	SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
Measure Participants	24	24
Number [participants]	0 0%	0 0%

Adverse Events

Time Frame	Day 1 of Period 1 up to the day of hospital discharge (Day 29) in Period 2
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 treatment.
Arm/Group Title	SYR-472 25 mg		SYR-472 50 mg
Arm/Group Description	SYR-472 25 mg, 2 tablets, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.		SYR-472 50 mg, tablet, once orally, on Day 1 of either Period 1 or Period 2. A washout of 13 days was maintained between the two periods.
All Cause Mortality
	SYR-472 25 mg		SYR-472 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	SYR-472 25 mg		SYR-472 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	SYR-472 25 mg		SYR-472 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No publication related to study results will be made without Sponsor's prior written approval. Any proposed publication or presentation will be submitted to Sponsor for review 60 days in advance of publication. Institution will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for an additional 60 days to preserve intellectual property.