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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1196-9223 | Other Identifier | WHO |
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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence I: ABCD | Experimental | SYR-322-4833 BL (alogliptin 25 [milligram] mg and pioglitazone 15 mg) 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). |
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| Sequence II: BCDA | Experimental | 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). |
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| Sequence III: CDAB | Experimental | 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). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alogliptin | Drug | Alogliptin tablets. |
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| Measure | Description | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Non-governmental healthcare Institution Road Clinical Hospital at the station Yaroslavl JSC Russian Railways | Yaroslavl | 150047 | Russia |
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 took part in the study at 1 investigative site in Russia from 26 May 2018 to 11 July 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Intervention Period 1 (4 Days) |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 23, 2018 | Jun 24, 2019 |
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| Sequence IV: DABC | Experimental | 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). |
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| Pioglitazone | Drug | Pioglitazone tablets. |
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| SYR-322-4833 BL | Drug | SYR-322-4833 BL FDC tablets. |
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| FG001 | 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). |
| FG002 | 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). |
| FG003 | 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). |
| Safety Analysis Set |
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| COMPLETED |
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| NOT COMPLETED |
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| Washout Period 1 (7 Days) |
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| Intervention Period 2 (4 Days) |
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| Washout Period 2 (7 Days) |
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| Intervention Period 3 (4 Days) |
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| Washout Period 3 (7 Days) |
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| Intervention Period 4 (4 Days) |
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The safety set included all randomized participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| BG001 | 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). |
| BG002 | 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). |
| BG003 | 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). |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Weight | Mean | Standard Deviation | kilogram (kg) |
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| Body mass index (BMI) | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
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| Height | Mean | Standard Deviation | centimeter (cm) |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Cmax: Maximum Observed Plasma Concentration for Alogliptin and Pioglitazone | 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. | Posted | Geometric Mean | Standard Deviation | nanogram per milliliter (ng/ml) | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
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| Primary | AUC(0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose for Alogliptin and Pioglitazone | 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. | Posted | Geometric Mean | Standard Deviation | hour*nanogram per milliliter (h*ng/mL) | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
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Treatment-emergent adverse events (TEAEs) are adverse events that started after the first dose of study drug and no more than 14 days (approximately Day 35) or 30 days (approximately Day 51) for a serious adverse event after the last dose of study drug
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Regimen A | SYR-322-4833 BL (alogliptin 25 mg and pioglitazone 15 mg) FDC tablet, orally, once, on Day 1 of Period 1, 2, 3 or 4. | 0 | 70 | 0 | 70 | 2 | 70 |
| EG001 | Regimen B | Alogliptin 25 mg tablet and pioglitazone 15 mg tablet, orally, once, on Day 1 of Period 1, 2, 3 or 4. | 0 | 69 | 0 | 69 | 1 | 69 |
| EG002 | Regimen C | SYR-322-4833 BL (alogliptin 25 mg and pioglitazone 30 mg) FDC tablet, orally, once, on Day 1 of Period 1, 2, 3 or 4. | 0 | 68 | 0 | 68 | 1 | 68 |
| EG003 | Regimen D | Alogliptin 25 mg tablet and pioglitazone 30 mg tablet, orally, once, on Day 1 of Period 1, 2, 3 or 4. | 0 | 70 | 0 | 70 | 2 | 70 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic oedema | Immune system disorders | MedDRA 21.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Hand fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 21.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
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Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 20, 2018 | Jun 24, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| C520853 | alogliptin |
| D000077205 | Pioglitazone |
| ID | Term |
|---|---|
| D045162 | Thiazolidinediones |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Pioglitazone |
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| ANOVA | 0.326 | LSM difference | 1.0276 | 2-Sided | 90 | 0.9817 | 1.0757 | Equivalence | Alogliptin: For each analyte, ANOVA was performed on natural logarithm transformed Cmax with factors for sequence, the participant nested within sequence, period, and regimen. For the relative BA determination, pairwise comparisons were performed to assess the relative BA of alogliptin and pioglitazone via point estimates and 90% CI for the ratio of Cmax for Regimen C (test) versus Regimen D (reference). |
| ANOVA | 0.405 | LSM diiference | 0.9594 | 2-Sided | 90 | 0.8837 | 1.0415 | Equivalence | Pioglitazone: For each analyte, ANOVA was performed on natural logarithm transformed Cmax with factors for sequence, the participant nested within sequence, period, and regimen. For the relative BA determination, pairwise comparisons were performed to assess the relative BA of alogliptin and pioglitazone via point estimates and 90% CI for the ratio of Cmax for Regimen A (test) versus Regimen B (reference). |
| ANOVA | 0.124 | LSM difference | 0.9257 | 2-Sided | 90 | 0.8523 | 1.0053 | Equivalence | Pioglitazone: For each analyte, ANOVA was performed on natural logarithm transformed Cmax with factors for sequence, the participant nested within sequence, period, and regimen. For the relative BA determination, pairwise comparisons were performed to assess the relative BA of alogliptin and pioglitazone via point estimates and 90% CI for the ratio of Cmax for Regimen C (test) versus Regimen D (reference). |
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