Trial Outcomes & Findings for Effect of Food on the Pharmacokinetics of Single Oral Dose Administration of a Fixed-Dose Combination of SYR-322 and Metformin Hydrochloride in Healthy Adult Male Subjects (NCT NCT02276274)

NCT ID: NCT02276274

Last Updated: 2023-09-21

Results Overview

AUC (0-72) is measure of area under the curve from time 0 to 72 hours post dose.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

12 participants

Primary outcome timeframe

3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Results posted on

2023-09-21

Participant Flow

Participants took part in the study at 1 investigative site in Japan from 21 June 2014 to 22 July 2014.

Healthy participants were enrolled in 1 of 2 treatment groups: SYR-322-MET fasted followed by SYR-322-MET fed; SYR-322-MET fed followed by SYR-322-MET fasted.

Participant milestones

Participant milestones
Measure
SYR-322-MET Fasted Followed by SYR-322-MET Fed
A single dose of SYR-322 25 milligram (mg) and metformin hydrochloride 500 mg in 1 tablet, orally under fasted condition on Day 1 of first intervention period, followed by at least 15 days of washout period, followed by a single dose of SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally under fed condition on Day 1 of second intervention period.
SYR-322-MET Fed Followed by SYR-322-MET Fasted
A single dose of SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally under fed condition on Day 1 of first intervention period, followed by at least 15 days of washout period, followed by a single dose of SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally under fasted condition on Day 1 of second intervention period.
First Intervention Period
STARTED
6
6
First Intervention Period
COMPLETED
6
6
First Intervention Period
NOT COMPLETED
0
0
Washout Period (at Least 15 Days)
STARTED
6
6
Washout Period (at Least 15 Days)
COMPLETED
6
6
Washout Period (at Least 15 Days)
NOT COMPLETED
0
0
Second Intervention Period
STARTED
6
6
Second Intervention Period
COMPLETED
6
6
Second Intervention Period
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Food on the Pharmacokinetics of Single Oral Dose Administration of a Fixed-Dose Combination of SYR-322 and Metformin Hydrochloride in Healthy Adult Male Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
SYR-322-MET Fasted Followed by SYR-322-MET Fed
n=6 Participants
A single dose of SYR-322 25 milligram (mg) and metformin hydrochloride 500 mg in 1 tablet, orally under fasted condition on Day 1 of first intervention period, followed by at least 15 days of washout period, followed by a single dose of SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally under fed condition on Day 1 of second intervention period.
SYR-322-MET Fed Followed by SYR-322-MET Fasted
n=6 Participants
A single dose of SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally under fed condition on Day 1 of first intervention period, followed by at least 15 days of washout period, followed by a single dose of SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally under fasted condition on Day 1 of second intervention period.
Total
n=12 Participants
Total of all reporting groups
Age, Continuous
23.2 years
STANDARD_DEVIATION 1.94 • n=5 Participants
27.2 years
STANDARD_DEVIATION 6.43 • n=7 Participants
25.2 years
STANDARD_DEVIATION 4.99 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
6 Participants
n=7 Participants
12 Participants
n=5 Participants
height
168.5 centimeters (cm)
STANDARD_DEVIATION 6.98 • n=5 Participants
175.7 centimeters (cm)
STANDARD_DEVIATION 6.68 • n=7 Participants
172.1 centimeters (cm)
STANDARD_DEVIATION 7.51 • n=5 Participants
Weight
61.17 kilogram (kg)
STANDARD_DEVIATION 8.373 • n=5 Participants
65.40 kilogram (kg)
STANDARD_DEVIATION 6.425 • n=7 Participants
63.28 kilogram (kg)
STANDARD_DEVIATION 7.451 • n=5 Participants
Body Mass Index (BMI)
21.48 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 1.878 • n=5 Participants
21.15 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 0.869 • n=7 Participants
21.32 kilogram per square meter (kg/m^2)
STANDARD_DEVIATION 1.406 • n=5 Participants
Smoking Classification
Never Smoked
2 participants
n=5 Participants
1 participants
n=7 Participants
3 participants
n=5 Participants
Smoking Classification
Current Smoker
3 participants
n=5 Participants
3 participants
n=7 Participants
6 participants
n=5 Participants
Smoking Classification
Ex-Smoker
1 participants
n=5 Participants
2 participants
n=7 Participants
3 participants
n=5 Participants
Alcohol Classification
Drank Every Day
0 participants
n=5 Participants
0 participants
n=7 Participants
0 participants
n=5 Participants
Alcohol Classification
Drank a Few Days per Week
0 participants
n=5 Participants
0 participants
n=7 Participants
0 participants
n=5 Participants
Alcohol Classification
Drank a Few Days per Month
4 participants
n=5 Participants
3 participants
n=7 Participants
7 participants
n=5 Participants
Alcohol Classification
No
2 participants
n=5 Participants
3 participants
n=7 Participants
5 participants
n=5 Participants
Caffeine Classification
Took Caffeine
2 participants
n=5 Participants
1 participants
n=7 Participants
3 participants
n=5 Participants
Caffeine Classification
Did not take Caffeine
4 participants
n=5 Participants
5 participants
n=7 Participants
9 participants
n=5 Participants

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

AUC (0-72) is measure of area under the curve from time 0 to 72 hours post dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Unchanged SYR-322 (SYR-322Z)
1494.9 nanogram*milliliter per hour (ng*hr/mL)
Standard Deviation 159.42
1472.8 nanogram*milliliter per hour (ng*hr/mL)
Standard Deviation 172.59

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

AUC (0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC \[0-tlqc\]).

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
AUC (0-tlqc): Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for SYR-322Z
1494.9 ng*hr/mL
Standard Deviation 159.42
1472.8 ng*hr/mL
Standard Deviation 172.59

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Cmax: Maximum Observed Plasma Concentration for SYR-322Z
154.9 ng/mL
Standard Deviation 38.72
173.4 ng/mL
Standard Deviation 38.45

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for SYR-322Z
3.000 hour (hr)
Interval 2.0 to 4.0
1.00 hour (hr)
Interval 0.5 to 3.0

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
AUC (0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for SYR-322Z
1555.0 ng*hr/mL
Standard Deviation 167.20
1536.8 ng*hr/mL
Standard Deviation 187.33

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Apparent Terminal Elimination Rate Constant (λz) for SYR-322Z
0.03912 hr^-1
Standard Deviation 0.0046649
0.03673 hr^-1
Standard Deviation 0.0053316

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Terminal Phase Elimination Half-life (T1/2) for SYR-322Z
17.94 hr
Standard Deviation 2.0527
19.24 hr
Standard Deviation 2.8931

PRIMARY outcome

Timeframe: 3 hours prior to administration, and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours after administration

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC (0-inf), expressed in liter/hour (L/hr).

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Apparent Clearance After Extra Vascular Administration (CL/F) for SYR-322Z
16.24 L/hr
Standard Deviation 1.6898
16.52 L/hr
Standard Deviation 2.2647

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Mean residence time (MRT) calculated as area under the first moment plasma concentration-time curve (AUMC \[0-inf\]) divided by AUC (0-inf). (AUMC \[0-inf\]) is the area under the first moment plasma concentration-time curve from time 0 to infinity.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Mean Residence Time (MRT) for SYR-322Z
18.06 hr
Standard Deviation 1.4216
17.72 hr
Standard Deviation 2.1696

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic analysis set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

MRT (0-tlqc) is a measure of the mean residence time from time 0 to time of the last quantifiable concentration (tlqc) calculated as MRT (0-tlqc) =AUMC (0-tlqc)/AUC (0-tlqc). AUMC (0-tlqc) is the area under the first moment plasma concentration-time curve from time 0 to time of the last quantifiable concentration (tlqc), calculated using the linear trapezoidal rule.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
MRT (0-tlqc): Mean Residence Time From Time 0 to Time of the Last Quantifiable Concentration (Tlqc) for SYR-322Z
14.84 hr
Standard Deviation 1.2056
14.17 hr
Standard Deviation 1.1703

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics of each of the SYR-322 metabolites.

AUC (0-72) is measure of area under the curve from time 0 to 72 hours post dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post Dose for SYR-322 Metabolites M-I and M-II
M-II
39.18 ng*hr/mL
Standard Deviation 26.439
37.00 ng*hr/mL
Standard Deviation 26.048
AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post Dose for SYR-322 Metabolites M-I and M-II
M-I
9.49 ng*hr/mL
Standard Deviation 7.746
8.28 ng*hr/mL
Standard Deviation 6.862

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics of each of the SYR-322 metabolites.

AUC (0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC \[0-tlqc\]).

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
AUC (0-tlqc): Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for SYR-322 Metabolites M-I and M-II
M-II
38.48 ng*hr/mL
Standard Deviation 26.579
36.00 ng*hr/mL
Standard Deviation 25.861
AUC (0-tlqc): Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for SYR-322 Metabolites M-I and M-II
M-I
8.93 ng*hr/mL
Standard Deviation 7.828
7.72 ng*hr/mL
Standard Deviation 6.906

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics of each of the SYR-322 metabolites.

MRT (0-tlqc) is a measure of the mean residence time from time 0 to time of the last quantifiable concentration (tlqc) calculated as MRT (0-tlqc) =AUMC (0-tlqc)/AUC (0-tlqc). AUMC (0-tlqc) is the area under the first moment plasma concentration-time curve from time 0 to time of the last quantifiable concentration (tlqc), calculated using the linear trapezoidal rule.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
MRT (0-tlqc): Mean Residence Time From Time 0 to Time of the Last Quantifiable Concentration (Tlqc) for SYR-322 Metabolites M-I and M-II
M-I (n= 11, 11)
17.95 hr
Standard Deviation 6.3662
17.75 hr
Standard Deviation 6.7278
MRT (0-tlqc): Mean Residence Time From Time 0 to Time of the Last Quantifiable Concentration (Tlqc) for SYR-322 Metabolites M-I and M-II
M-II (n=12, 12)
10.88 hr
Standard Deviation 1.6364
10.45 hr
Standard Deviation 1.7285

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics of each of the SYR-322 metabolites.

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Cmax: Maximum Observed Plasma Concentration for SYR-322 Metabolites M-I and M-II
M-I
0.42 ng/mL
Standard Deviation 0.295 • Interval 1.5 to 4.0
0.40 ng/mL
Standard Deviation 0.319 • Interval 1.0 to 4.0
Cmax: Maximum Observed Plasma Concentration for SYR-322 Metabolites M-I and M-II
M-II
4.18 ng/mL
Standard Deviation 3.052 • Interval 3.0 to 4.0
3.58 ng/mL
Standard Deviation 2.525 • Interval 1.5 to 3.0

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics of each of the SYR-322 metabolites.

Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for SYR-322 Metabolites M-I and M-II
M-I (n = 11, 11)
3.000 hr
Full Range 9.168 • Interval 1.5 to 4.0
1.500 hr
Full Range 6.369 • Interval 1.0 to 4.0
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for SYR-322 Metabolites M-I and M-II
M-II (n = 12, 12)
3.000 hr
Full Range 27.226 • Interval 3.0 to 4.0
2.500 hr
Full Range 26.671 • Interval 1.5 to 3.0

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics of each of the SYR-322 metabolites.

AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
AUC (0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for SYR-322 Metabolites M-I and M-II
M-I (n = 9, 9)
15.86 ng*hr/mL
Standard Deviation 9.168
14.53 ng*hr/mL
Standard Deviation 6.369
AUC (0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for SYR-322 Metabolites M-I and M-II
M-II (n = 12, 12)
40.28 ng*hr/mL
Standard Deviation 27.226
38.01 ng*hr/mL
Standard Deviation 26.671

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics of each of the SYR-322 metabolites.

Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Apparent Terminal Elimination Rate Constant (λz) for SYR-322 Metabolites M-I and M-II
M-I (n = 9, 9)
0.02711 hr^-1
Standard Deviation 0.0039065
0.02708 hr^-1
Standard Deviation 0.0081278
Apparent Terminal Elimination Rate Constant (λz) for SYR-322 Metabolites M-I and M-II
M-II (n = 12, 12)
0.06458 hr^-1
Standard Deviation 0.023460
0.06651 hr^-1
Standard Deviation 0.021985

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics of each of the SYR-322 metabolites.

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Terminal Phase Elimination Half-life (T1/2) for SYR-322 Metabolites M-I and M-II
M-I (n = 9, 9)
26.09 hr
Standard Deviation 3.9939
31.39 hr
Standard Deviation 22.996
Terminal Phase Elimination Half-life (T1/2) for SYR-322 Metabolites M-I and M-II
M-II (n = 12, 12)
12.43 hr
Standard Deviation 5.4904
11.70 hr
Standard Deviation 4.5855

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics of each of the SYR-322 metabolites.

Mean residence time (MRT) calculated as area under the first moment plasma concentration-time curve (AUMC \[0-inf\]) divided by AUC (0-inf). AUMC (0-inf) is the area under the first moment plasma concentration-time curve from time 0 to infinity.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Mean Residence Time (MRT) for SYR-322 Metabolites M-I and M-II
M-I (n = 9, 9)
39.87 hr
Standard Deviation 6.1272
49.97 hr
Standard Deviation 38.556
Mean Residence Time (MRT) for SYR-322 Metabolites M-I and M-II
M-II (n = 12, 12)
13.93 hr
Standard Deviation 2.2797
13.81 hr
Standard Deviation 2.1894

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

AUC (0-48) is measure of area under the curve from time 0 to 48 hours post dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
AUC (0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for Metformin
9157.3 ng*hr/mL
Standard Deviation 1684.53
8991.8 ng*hr/mL
Standard Deviation 1284.97

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

AUC (0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC \[0-tlqc\]).

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
AUC (0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Metformin
9038.8 ng*hr/mL
Standard Deviation 1661.09
8853.8 ng*hr/mL
Standard Deviation 1271.92

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: Subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

MRT (0-tlqc) is a measure of the mean residence time from time 0 to time of the last quantifiable concentration (tlqc) calculated as MRT (0-tlqc) =AUMC (0-tlqc)/AUC (0-tlqc). AUMC (0-tlqc) is the area under the first moment plasma concentration-time curve from time 0 to time of the last quantifiable concentration (tlqc), calculated using the linear trapezoidal rule.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
MRT (0-tlqc): Mean Residence Time From Time 0 to Time of the Last Quantifiable Concentration (Tlqc) for Metformin
5.697 hr
Standard Deviation 0.75798
5.697 hr
Standard Deviation 0.58215

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Cmax: Maximum Observed Plasma Concentration for Metformin
1473.3 ng/mL
Standard Deviation 300.19
1251.7 ng/mL
Standard Deviation 164.03

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Metformin
3.000 hr
Interval 0.5 to 4.0
3.000 hr
Interval 0.5 to 4.0

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
AUC (0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Metformin
9195.3 ng*hr/mL
Standard Deviation 1669.37
8997.4 ng*hr/mL
Standard Deviation 1289.67

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Apparent Terminal Elimination Rate Constant (λz) for Metformin
0.1366 hr^-1
Standard Deviation 0.028295
0.1638 hr^-1
Standard Deviation 0.027820

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Terminal Phase Elimination Half-life (T1/2) for Metformin
5.290 hr
Standard Deviation 1.1735
4.338 hr
Standard Deviation 0.70681

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC (0-inf), expressed in L/hr.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Apparent Clearance After Extra Vascular Administration (CL/F) for Metformin
55.84 L/hr
Standard Deviation 9.0078
56.75 L/hr
Standard Deviation 9.1099

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Mean residence time (MRT) calculated as area under the first moment plasma concentration-time curve (AUMC \[0-inf\]) divided by AUC (0-inf). AUMC (0-inf) is the area under the first moment plasma concentration-time curve from time 0 to infinity.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Mean Residence Time (MRT) for Metformin
6.213 hr
Standard Deviation 0.88315
6.097 hr
Standard Deviation 0.63435

PRIMARY outcome

Timeframe: 0 to 12 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of unchanged SYR-322 was calculated as the percentage of SYR-322 dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of SYR-322Z From 0 to 12 Hours Postdose
42.609 percentage of dose
Standard Deviation 4.9985
45.028 percentage of dose
Standard Deviation 6.9388

PRIMARY outcome

Timeframe: 0 to 24 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of unchanged SYR-322 was calculated as the percentage of SYR-322 dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of SYR-322Z From 0 to 24 Hours Postdose
58.618 percentage of dose
Standard Deviation 4.0606
59.886 percentage of dose
Standard Deviation 6.5474

PRIMARY outcome

Timeframe: 0 to 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of unchanged SYR-322 was calculated as the percentage of SYR-322 dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of SYR-322Z From 0 to 48 Hours Postdose
70.200 percentage of dose
Standard Deviation 3.8051
71.148 percentage of dose
Standard Deviation 6.4985

PRIMARY outcome

Timeframe: 0 to 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of unchanged SYR-322 was calculated as the percentage of SYR-322 dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of SYR-322Z From 0 to 72 Hours Postdose
73.728 percentage of dose
Standard Deviation 3.9140
74.547 percentage of dose
Standard Deviation 6.4048

PRIMARY outcome

Timeframe: 0 to 12 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of SYR-322 metabolites M-I and M-II was calculated as the percentage of SYR-322 dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 12 Hours Postdose
M-I
0.235 percentage of dose
Standard Deviation 0.1393
0.234 percentage of dose
Standard Deviation 0.1719
Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 12 Hours Postdose
M-II
1.202 percentage of dose
Standard Deviation 0.8060
1.145 percentage of dose
Standard Deviation 0.7826

PRIMARY outcome

Timeframe: 0 to 24 hours post dose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of SYR-322 metabolites M-I and M-II was calculated as the percentage of SYR-322 dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 24 Hours Postdose
M-I
0.394 percentage of dose
Standard Deviation 0.2386
0.363 percentage of dose
Standard Deviation 0.2482
Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 24 Hours Postdose
M-II
1.562 percentage of dose
Standard Deviation 1.0106
1.502 percentage of dose
Standard Deviation 0.9879

PRIMARY outcome

Timeframe: 0 to 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of SYR-322 metabolites M-I and M-II was calculated as the percentage of SYR-322 dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 48 Hours Postdose
M-I
0.535 percentage of dose
Standard Deviation 0.3441
0.495 percentage of dose
Standard Deviation 0.3352
Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 48 Hours Postdose
M-II
1.788 percentage of dose
Standard Deviation 1.1384
1.732 percentage of dose
Standard Deviation 1.1284

PRIMARY outcome

Timeframe: 0 to 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of SYR-322 metabolites M-I and M-II was calculated as the percentage of SYR-322 dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 72 Hours Postdose
M-I
0.588 percentage of dose
Standard Deviation 0.3884
0.536 percentage of dose
Standard Deviation 0.3816
Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 72 Hours Postdose
M-II
1.853 percentage of dose
Standard Deviation 1.1929
1.796 percentage of dose
Standard Deviation 1.1696

PRIMARY outcome

Timeframe: 0 to 12 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of metformin was calculated as the percentage of metformin dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of Metformin From Time 0 to 12 Hours Postdose
45.143 percentage of dose
Standard Deviation 7.7692
44.809 percentage of dose
Standard Deviation 7.4874

PRIMARY outcome

Timeframe: 0 to 24 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of metformin was calculated as the percentage of metformin dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of Metformin From 0 to 24 Hours Postdose
50.078 percentage of dose
Standard Deviation 7.5995
49.923 percentage of dose
Standard Deviation 7.5189

PRIMARY outcome

Timeframe: 0 to 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

Cumulative urinary excretion ratio of metformin was calculated as the percentage of metformin dose.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Urinary Excretion Ratio of Metformin From 0 to 48 Hours Postdose
50.626 percentage of dose
Standard Deviation 7.6377
50.067 percentage of dose
Standard Deviation 7.6636

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

CLr is a measure of apparent clearance of the drug from the urine. The clearance is the rate at which waste substances are cleared from the blood.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
CLr: Renal Clearance of SYR-322Z
11.96 L/hr
Standard Deviation 1.2071
12.33 L/hr
Standard Deviation 2.2296

PRIMARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose

Population: Pharmacokinetic set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacokinetics.

CLr is a measure of apparent clearance of the drug from the urine.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
CLr: Renal Clearance of Metformin
27.88 L/hr
Standard Deviation 4.1525
28.34 L/hr
Standard Deviation 6.3364

SECONDARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours postdose

Population: Pharmacodynamic analysis set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacodynamics.

DPP-4 activity and inhibition rate of DPP-4 activity was assessed from the plasma samples collected from the participants. Inhibition of DPP-4 enzyme was used to determine the antihyperglycemic activity of the investigational product.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
Predose
0.00 percentage of inhibition
Standard Deviation 0.000
0.00 percentage of inhibition
Standard Deviation 0.000
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
0.25 hour
68.00 percentage of inhibition
Standard Deviation 26.599
57.99 percentage of inhibition
Standard Deviation 32.209
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
0.5 hour
85.65 percentage of inhibition
Standard Deviation 17.721
90.31 percentage of inhibition
Standard Deviation 7.533
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
1 hour
91.05 percentage of inhibition
Standard Deviation 4.070
95.27 percentage of inhibition
Standard Deviation 2.371
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
1.5 hour
91.85 percentage of inhibition
Standard Deviation 2.342
95.79 percentage of inhibition
Standard Deviation 0.710
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
2 hour
93.63 percentage of inhibition
Standard Deviation 2.028
95.58 percentage of inhibition
Standard Deviation 0.542
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
3 hour
95.52 percentage of inhibition
Standard Deviation 1.528
94.71 percentage of inhibition
Standard Deviation 0.611
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
4 hour
94.88 percentage of inhibition
Standard Deviation 1.216
93.78 percentage of inhibition
Standard Deviation 0.877
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
6 hour
93.04 percentage of inhibition
Standard Deviation 0.708
92.06 percentage of inhibition
Standard Deviation 0.880
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
8 hour
91.78 percentage of inhibition
Standard Deviation 0.890
90.51 percentage of inhibition
Standard Deviation 1.071
Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity
24 hour
81.74 percentage of inhibition
Standard Deviation 2.235
81.38 percentage of inhibition
Standard Deviation 2.614

SECONDARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours postdose

Population: Pharmacodynamic analysis set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacodynamics.

DPP-4 activity was assessed from the plasma samples collected from the participants.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
DPP-4 Activity
0.25 hour
2.5833 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 2.37291
3.4518 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 2.86390
DPP-4 Activity
0.5 hour
1.1944 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 1.64100
0.7823 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.66267
DPP-4 Activity
1 Hour
0.7122 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.39573
0.3737 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.21081
DPP-4 Activity
1.5 Hour
0.6366 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.19955
0.3312 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.07085
DPP-4 Activity
2 hours
0.5003 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.17621
0.3475 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.05993
DPP-4 Activity
3 hours
0.3575 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.14924
0.4128 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.06132
DPP-4 Activity
Predose
7.8167 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.85551
7.8492 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.99173
DPP-4 Activity
4 hours
0.3977 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.09285
0.4873 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.08441
DPP-4 Activity
6 hours
0.5423 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.07347
0.6196 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.08548
DPP-4 Activity
8 hours
0.6422 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.09457
0.7425 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.11652
DPP-4 Activity
24 hours
1.4275 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.22071
1.4550 nanomole/minute/milliliter (nmoL/min/mL)
Standard Deviation 0.24055

SECONDARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours postdose

Population: Pharmacodynamic analysis set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacodynamics.

Area under the inhibition rate of plasma DPP-4 activity-time curve from time 0 to 24 hours was determined from the inhibition-time curve.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
AUC (0-24): Area Under the Inhibition Rate of Plasma DPP-4 Activity-time Curve From Time 0 to 24 Hours
2114.62 percentage of inhibition*hour
Standard Deviation 30.355
2100.74 percentage of inhibition*hour
Standard Deviation 27.297

SECONDARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours postdose

Population: Pharmacodynamic analysis set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacodynamics.

Maximum inhibition rate of plasma DPP-4 activity was determined from the inhibition-time curve.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Emax: Maximum Inhibition Rate of Plasma DPP-4 Activity
96.10 percentage of inhibition
Standard Deviation 1.022
96.33 percentage of inhibition
Standard Deviation 0.779

SECONDARY outcome

Timeframe: 3 hours prior to administration (predose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours postdose

Population: Pharmacodynamic analysis set: subset of participants who received the investigational product, satisfied the minimum requirements of the protocol with no significant deviations, and were assessable for pharmacodynamics.

Time to reach Emax for the first time was determined from the inhibition-time curve.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Tmax: Time to Reach Emax
3.000 hour
Interval 2.0 to 4.0
1.000 hour
Interval 0.5 to 2.0

SECONDARY outcome

Timeframe: Baseline up to the day of discharge (Day 4) in the second intervention period

Population: Safety analysis set: All participants who receive at least one dose of study medication.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Number of Participants Reporting 1 or More Treatment-emergent Adverse Events
0 participants
0 participants

SECONDARY outcome

Timeframe: 3 hours prior to administration (predose) and 2, 24 and 72 hours postdose

Population: Safety analysis set: All participants who receive at least one dose of study medication.

Vital signs included body temperature (infra-axillary), supine blood pressure resting more than 5 minutes (systolic and diastolic \[Millimeters of mercury\]), respiratory rate and pulse (beats per minute). Clinically significant change in vital signs observed at any time point are reported.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
0 participants
0 participants

SECONDARY outcome

Timeframe: 3 hours prior to administration (predose), 24 and 72 hours postdose

Population: Safety analysis set: All participants who receive at least one dose of study medication.

Clinically significant change participant's body weight observed at any time point are reported.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Number of Participants With Clinically Significant Change From Baseline in Body Weight
0 participants
0 participants

SECONDARY outcome

Timeframe: 3 hours prior to administration (predose) and 2, 24 and 72 hours postdose

Population: Safety analysis set: All participants who receive at least one dose of study medication.

Clinically significant change in electrocardiograms observed at any time point are reported.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Number of Participants With Significant Change From Baseline in Electrocardiograms
0 participants
0 participants

SECONDARY outcome

Timeframe: 3 hours prior to administration (predose), 24 and 72 hours postdose

Population: Safety analysis set: All participants who receive at least one dose of study medication.

Laboratory assessments included hematology, serum chemistry and urinalysis. Any laboratory-related TEAE reported at any time point were reported in this measure.

Outcome measures

Outcome measures
Measure
SYR-322-MET Fasted
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fasted condition on Day 1 of either first or second intervention period.
SYR-322-MET Fed
n=12 Participants
SYR-322 25 mg and metformin hydrochloride 500 mg in 1 tablet, orally, under fed condition on Day 1 of either first or second intervention period.
Number of Participants With Laboratory-related Treatment Emergent Adverse Events (TEAEs)
0 participants
0 participants

Adverse Events

SYR-322-MET Fasted

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

SYR-322-MET Fed

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Study Director

Takeda (Note: This product was divested to Teijin Pharma Limited in 2023)

Phone: +1-877-825-3327

Results disclosure agreements

  • Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
  • Publication restrictions are in place

Restriction type: OTHER