Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to assess the relative bioavailability and bioequivalence of 2 strengths of the FDC tablet product SYR-322-4833 BL compared to the individual alogliptin and pioglitazone tablets in healthy Russian participants.
Detailed description
The drug being tested in this study are called Incresync (SYR-322-4833 BL), alogliptin, and pioglitazone. This study will assess the bioequivalence, pharmacokinetics (PK), and safety of alogliptin and pioglitazone administered as individual tablets and as the FDC tablet product in healthy volunteers. The study will enroll approximately 72 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 4 treatment sequences to receive one of the following treatments: * Regimen A: SYR-322-4833 BL (25 mg + 15 mg) * Regimen B: Alogliptin 25 mg + pioglitazone 15 mg * Regimen C: SYR-322-4833 BL (25 mg + 30 mg) * Regimen D: Alogliptin 25 mg + pioglitazone 30 mg All participants will be asked to take single dose of study medication on Day 1 of each intervention period. This single center trial will be conducted in Russia. The overall time to participate in this study is 66 days. Participants will make multiple visits to the clinic, and will be contacted by telephone 14 days after their last dose of drug for a follow-up assessment.
Interventions
DRUGAlogliptin
Alogliptin tablets.
DRUGPioglitazone
Pioglitazone tablets.
DRUGSYR-322-4833 BL
SYR-322-4833 BL FDC tablets.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Is a healthy male or female. 2. Has an estimated glomerular filtration rate (eGFR) greater than or equal to (\>=) 90 milliliter per minute (mL/min). 3. Weighs at least 50 kilogram (kg) and has a body mass index (BMI) from 18.5 to 30.0 kilogram per square meter (kg/m\^2), inclusive at Screening.
Exclusion criteria
1. Has participated in a clinical study within 3 months prior to Check-in (Day-1). 2. Has a fasting blood glucose level lower than 3.88 millimole per liter (mmol/L). 3. Has received alogliptin or pioglitazone in a previous clinical study or as a therapeutic agent within 90 days prior to Check-in (Day-1). 4. Experienced acute infectious diseases within 4 weeks prior to Screening. 5. Has a positive urine drug result for super potent substances and drugs of abuse (defined as any illicit drug use) or positive alcohol breath test at Screening or Check-in (Day -1). 6. Consumes over 10 drinks weekly (1 drink is equivalent to 0.5 liters of beer, 200 milliliter (mL) of dry wine or 50 mL of ardent spirits) or has a history of alcoholism, drug and/or substance abuse. 7. Has a non-standard diet (example, vegetarian or vegan) or lifestyle (including night time work, extreme physical activity such as weights lifting), which may interfere with the trial. 8. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in Day -1. Cotinine test is positive at Screening or Check-in (Day -1). 9. Has poor peripheral venous access. 10. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1 of Period 1. 11. Has consumed caffeine or xanthine-containing food or drinks within 72 hours prior to Check-in (Day -1). 12. Has dehydration due to vomiting, diarrhea, or any other reason within 24 hours prior to study start. 13. Has drug intolerance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
Countries
Russia
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in Russia from 26 May 2018 to 11 July 2018.
Pre-assignment details
Healthy participants were enrolled in 1 of the 4 treatment sequences to receive: SYR-322-4833 BL (25 milligram \[mg\] + 15 mg) (Regimen A), alogliptin 25 mg + pioglitazone 15 mg (Regimen B), SYR-322-4833 (25 mg + 30 mg) (Regimen C), and alogliptin 25 mg + pioglitazone 30 mg (Regimen D).
Participants by arm
| Arm | Count |
|---|---|
| Sequence I: ABCD SYR-322-4833 BL (alogliptin 25 mg and pioglitazone 15 mg) fixed dose combination (FDC) tablet, orally, once, on Day 1 of Period 1 (Regimen A), followed by a 7-day washout period, followed by alogliptin 25 mg tablet and pioglitazone 15 mg tablet, orally, once, on Day 1 of Period 2 (Regimen B), followed by a 7-day washout period, followed by SYR-322-4833 BL (alogliptin 25 mg and pioglitazone 30 mg) FDC tablet, orally, once, on Day 1 of Period 3 (Regimen C), followed by a 7-day washout period, followed by alogliptin 25 mg tablet and pioglitazone 30 mg tablet, orally, once, on Day 1 of Period 4 (Regimen D). | 18 |
| Sequence II: BCDA Alogliptin 25 mg tablet and pioglitazone 15 mg tablet, orally, once, on Day 1 of Period 1 (Regimen B), followed by a 7-day washout period, followed by SYR-322-4833 BL (alogliptin 25 mg and pioglitazone 30 mg) FDC tablet, orally, once, on Day 1 of Period 2 (Regimen C), followed by a 7-day washout period, followed by alogliptin 25 mg tablet and pioglitazone 30 mg tablet, orally, once, on Day 1 of Period 3 (Regimen D), followed by a 7-day washout period, followed by SYR-322-4833 BL (alogliptin 25 mg and pioglitazone 15 mg) FDC tablet, orally, once, on Day 1 of Period 4 (Regimen A). | 18 |
| Sequence III: CDAB SYR-322-4833 BL (alogliptin 25 mg and pioglitazone 30 mg) FDC tablet, orally, once, on Day 1 of Period 1 (Regimen C), followed by a 7-day washout period, followed by alogliptin 25 mg tablet and pioglitazone 30 mg tablet, orally, once, on Day 1 of Period 2 (Regimen D), followed by a 7-day washout period, followed by SYR-322-4833 BL (alogliptin 25 mg and pioglitazone 15 mg) FDC tablet, orally, once, on Day 1 of Period 3 (Regimen A), followed by a 7-day washout period, followed by alogliptin 25 mg tablet and pioglitazone 15 mg tablet, orally, once, on Day 1 of Period 4 (Regimen B). | 17 |
| Sequence IV: DABC Alogliptin 25 mg tablet and pioglitazone 30 mg tablet, orally, once, on Day 1 of Period 1 (Regimen D), followed by a 7-day washout period, followed by SYR-322-4833 BL (alogliptin 25 mg and pioglitazone 15 mg) FDC tablet, orally, once, on Day 1 of Period 2 (Regimen A), followed by a 7-day washout period, followed by alogliptin 25 mg tablet and pioglitazone 15 mg tablet, orally, once, on Day 1 of Period 3 (Regimen B), followed by a 7-day washout period, followed by SYR-322-4833 BL (alogliptin 25 mg and pioglitazone 30 mg) FDC tablet, orally, once, on Day 1 of Period 4 (Regimen C). | 17 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Intervention Period 1 (4 Days) | Adverse Event | 0 | 0 | 0 | 1 |
| Intervention Period 1 (4 Days) | Other | 0 | 0 | 1 | 0 |
| Intervention Period 2 (4 Days) | Adverse Event | 0 | 0 | 0 | 1 |
| Intervention Period 3 (4 Days) | Adverse Event | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Sequence III: CDAB | Sequence I: ABCD | Sequence IV: DABC | Sequence II: BCDA |
|---|---|---|---|---|---|
| Age, Continuous | 27.4 years STANDARD_DEVIATION 7.18 | 29.4 years STANDARD_DEVIATION 8.46 | 28.9 years STANDARD_DEVIATION 7.95 | 27.5 years STANDARD_DEVIATION 6.36 | 23.9 years STANDARD_DEVIATION 4.6 |
| Body mass index (BMI) | 24.48 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.342 | 24.78 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.575 | 24.21 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.411 | 24.89 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.628 | 24.06 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.959 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants | 17 Participants | 18 Participants | 17 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 170.0 centimeter (cm) STANDARD_DEVIATION 9.14 | 173.6 centimeter (cm) STANDARD_DEVIATION 10.22 | 168.3 centimeter (cm) STANDARD_DEVIATION 8.56 | 168.4 centimeter (cm) STANDARD_DEVIATION 9.44 | 169.9 centimeter (cm) STANDARD_DEVIATION 8.02 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 70 Participants | 17 Participants | 18 Participants | 17 Participants | 18 Participants |
| Region of Enrollment Russia | 70 Participants | 17 Participants | 18 Participants | 17 Participants | 18 Participants |
| Sex: Female, Male Female | 33 Participants | 8 Participants | 9 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Male | 37 Participants | 9 Participants | 9 Participants | 8 Participants | 11 Participants |
| Weight | 71.17 kilogram (kg) STANDARD_DEVIATION 13.806 | 75.06 kilogram (kg) STANDARD_DEVIATION 14.643 | 68.77 kilogram (kg) STANDARD_DEVIATION 12.527 | 71.22 kilogram (kg) STANDARD_DEVIATION 15.894 | 69.86 kilogram (kg) STANDARD_DEVIATION 12.409 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 69 | 0 / 68 | 0 / 70 |
| other Total, other adverse events | 2 / 70 | 1 / 69 | 1 / 68 | 2 / 70 |
| serious Total, serious adverse events | 0 / 70 | 0 / 69 | 0 / 68 | 0 / 70 |
Outcome results
Primary
AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The PK analysis set included all participants in the safety set who had sufficient plasma concentration data to facilitate the derivation of at least 1 PK parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen A | AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone | Alogliptin | 2197.3 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 340.92 |
| Regimen A | AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone | Pioglitazone | 5726.0 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 1826.18 |
| Regimen B | AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone | Pioglitazone | 5471.9 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 1766.76 |
| Regimen B | AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone | Alogliptin | 2163.4 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 362.83 |
| Regimen C | AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone | Alogliptin | 2194.7 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 379.27 |
| Regimen C | AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone | Pioglitazone | 10141.6 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 3611.38 |
| Regimen D | AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone | Alogliptin | 2195.0 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 379.8 |
| Regimen D | AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone | Pioglitazone | 9907.6 hour*nanogram per milliliter (h*ng/mL) | Standard Deviation 3495.57 |
p-value: 0.08190% CI: [1.0009, 1.0308]ANOVA
p-value: 0.92290% CI: [0.9862, 1.0158]ANOVA
p-value: 0.06690% CI: [1.0051, 1.0939]ANOVA
p-value: 0.30890% CI: [0.9839, 1.0714]ANOVA
Primary
Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Population: The pharmacokinetic (PK) analysis set included all participants in the safety set who had sufficient plasma concentration data to facilitate the derivation of at least 1 PK parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regimen A | Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone | Alogliptin | 165.3 nanogram per milliliter (ng/ml) | Standard Deviation 42.87 |
| Regimen A | Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone | Pioglitazone | 678.3 nanogram per milliliter (ng/ml) | Standard Deviation 267.58 |
| Regimen B | Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone | Pioglitazone | 706.5 nanogram per milliliter (ng/ml) | Standard Deviation 254.12 |
| Regimen B | Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone | Alogliptin | 154.9 nanogram per milliliter (ng/ml) | Standard Deviation 44.71 |
| Regimen C | Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone | Alogliptin | 162.3 nanogram per milliliter (ng/ml) | Standard Deviation 51.19 |
| Regimen C | Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone | Pioglitazone | 1052.1 nanogram per milliliter (ng/ml) | Standard Deviation 478.13 |
| Regimen D | Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone | Alogliptin | 157.4 nanogram per milliliter (ng/ml) | Standard Deviation 44.24 |
| Regimen D | Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone | Pioglitazone | 1141.5 nanogram per milliliter (ng/ml) | Standard Deviation 509.78 |
p-value: 0.01490% CI: [1.023, 1.1204]ANOVA
p-value: 0.32690% CI: [0.9817, 1.0757]ANOVA
p-value: 0.40590% CI: [0.8837, 1.0415]ANOVA
p-value: 0.12490% CI: [0.8523, 1.0053]ANOVA