Phase 3 N=12 Randomized Basic Science

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

Clinical Pharmacology

Bottom Line

View on ClinicalTrials.gov: NCT02276274 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jun 2015

Primary outcome: Primary: 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; 1472.8 nanogram*milliliter per hour (ng*hr/mL)

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: SYR-322-MET (Drug)
Age: Adult · 20+ yrs
Sex: Male
Sponsor: Takeda
Primary completion: Jun 2014

Outcome Measures

Outcome	Result	p-value
PRIMARY 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; 1472.8	—
PRIMARY 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; 1472.8	—
PRIMARY Cmax: Maximum Observed Plasma Concentration for SYR-322Z	154.9; 173.4	—
PRIMARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for SYR-322Z	3.000; 1.00	—
PRIMARY AUC (0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for SYR-322Z	1555.0; 1536.8	—
PRIMARY Apparent Terminal Elimination Rate Constant (λz) for SYR-322Z	0.03912; 0.03673	—
PRIMARY Terminal Phase Elimination Half-life (T1/2) for SYR-322Z	17.94; 19.24	—
PRIMARY Apparent Clearance After Extra Vascular Administration (CL/F) for SYR-322Z	16.24; 16.52	—
PRIMARY Mean Residence Time (MRT) for SYR-322Z	18.06; 17.72	—
PRIMARY MRT (0-tlqc): Mean Residence Time From Time 0 to Time of the Last Quantifiable Concentration (Tlqc) for SYR-322Z	14.84; 14.17	—
PRIMARY 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	9.49; 8.28; 39.18; 37.00	—
PRIMARY 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	8.93; 7.72; 38.48; 36.00	—
PRIMARY 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	17.95; 17.75; 10.88; 10.45	—
PRIMARY Cmax: Maximum Observed Plasma Concentration for SYR-322 Metabolites M-I and M-II	0.42; 0.40; 4.18; 3.58	—
PRIMARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for SYR-322 Metabolites M-I and M-II	3.000; 1.500; 3.000; 2.500	—
PRIMARY AUC (0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for SYR-322 Metabolites M-I and M-II	15.86; 14.53; 40.28; 38.01	—
PRIMARY Apparent Terminal Elimination Rate Constant (λz) for SYR-322 Metabolites M-I and M-II	0.02711; 0.02708; 0.06458; 0.06651	—
PRIMARY Terminal Phase Elimination Half-life (T1/2) for SYR-322 Metabolites M-I and M-II	26.09; 31.39; 12.43; 11.70	—
PRIMARY Mean Residence Time (MRT) for SYR-322 Metabolites M-I and M-II	39.87; 49.97; 13.93; 13.81	—
PRIMARY AUC (0-48): Area Under the Plasma Concentration-time Curve From Time 0 to 48 Hours Postdose for Metformin	9157.3; 8991.8	—
PRIMARY 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; 8853.8	—
PRIMARY MRT (0-tlqc): Mean Residence Time From Time 0 to Time of the Last Quantifiable Concentration (Tlqc) for Metformin	5.697; 5.697	—
PRIMARY Cmax: Maximum Observed Plasma Concentration for Metformin	1473.3; 1251.7	—
PRIMARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Metformin	3.000; 3.000	—
PRIMARY AUC (0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Metformin	9195.3; 8997.4	—
PRIMARY Apparent Terminal Elimination Rate Constant (λz) for Metformin	0.1366; 0.1638	—
PRIMARY Terminal Phase Elimination Half-life (T1/2) for Metformin	5.290; 4.338	—
PRIMARY Apparent Clearance After Extra Vascular Administration (CL/F) for Metformin	55.84; 56.75	—
PRIMARY Mean Residence Time (MRT) for Metformin	6.213; 6.097	—
PRIMARY Urinary Excretion Ratio of SYR-322Z From 0 to 12 Hours Postdose	42.609; 45.028	—
PRIMARY Urinary Excretion Ratio of SYR-322Z From 0 to 24 Hours Postdose	58.618; 59.886	—
PRIMARY Urinary Excretion Ratio of SYR-322Z From 0 to 48 Hours Postdose	70.200; 71.148	—
PRIMARY Urinary Excretion Ratio of SYR-322Z From 0 to 72 Hours Postdose	73.728; 74.547	—
PRIMARY Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 12 Hours Postdose	0.235; 0.234; 1.202; 1.145	—
PRIMARY Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 24 Hours Postdose	0.394; 0.363; 1.562; 1.502	—
PRIMARY Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 48 Hours Postdose	0.535; 0.495; 1.788; 1.732	—
PRIMARY Urinary Excretion Ratio of SYR-322 Metabolites M-I and M-II From 0 to 72 Hours Postdose	0.588; 0.536; 1.853; 1.796	—
PRIMARY Urinary Excretion Ratio of Metformin From Time 0 to 12 Hours Postdose	45.143; 44.809	—
PRIMARY Urinary Excretion Ratio of Metformin From 0 to 24 Hours Postdose	50.078; 49.923	—
PRIMARY Urinary Excretion Ratio of Metformin From 0 to 48 Hours Postdose	50.626; 50.067	—
PRIMARY CLr: Renal Clearance of SYR-322Z	11.96; 12.33	—
PRIMARY CLr: Renal Clearance of Metformin	27.88; 28.34	—
SECONDARY Inhibition Rate of Dipeptidyl-peptidase-4 (DPP-4) Activity	0.00; 0.00; 68.00; 57.99; 85.65; 90.31	—
SECONDARY DPP-4 Activity	7.8167; 7.8492; 2.5833; 3.4518; 1.1944; 0.7823	—
SECONDARY AUC (0-24): Area Under the Inhibition Rate of Plasma DPP-4 Activity-time Curve From Time 0 to 24 Hours	2114.62; 2100.74	—
SECONDARY Emax: Maximum Inhibition Rate of Plasma DPP-4 Activity	96.10; 96.33	—
SECONDARY Tmax: Time to Reach Emax	3.000; 1.000	—
SECONDARY Number of Participants Reporting 1 or More Treatment-emergent Adverse Events	0; 0	—
SECONDARY Number of Participants With Clinically Significant Change From Baseline in Vital Signs	0; 0	—
SECONDARY Number of Participants With Clinically Significant Change From Baseline in Body Weight	0; 0	—
SECONDARY Number of Participants With Significant Change From Baseline in Electrocardiograms	0; 0	—
SECONDARY Number of Participants With Laboratory-related Treatment Emergent Adverse Events (TEAEs)	0; 0	—

Summary

This is a randomized, open-label, crossover study to determine the effect of food when a combination tablet of SYR-322 and metformin hydrochloride ( hereinafter referred to as SYR-322-MET tablet) is orally administered under fasting conditions in the morning or after breakfast in Japanese healthy adult male subjects.

Eligibility Criteria

Inclusion Criteria

In the opinion of the investigator or subinvestigator, the subject is capable of understanding and complying with protocol requirements.
The subject signs and dates a written, informed consent form prior to the initiation of any study procedures.
The subject is a Japanese healthy adult male.
The subject is aged 20 to 35 years, inclusive, at the time of informed consent.
The subject has a body weight of 50 kg or more with a BMI of ≥18.5 kg/m2 and 1.5 the upper limits of normal.
Subject who, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for any other reason.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02276274). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.