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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1159-5909 | Registry Identifier | WHO |
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The purpose of this study is to evaluate the relative bioavailability of a new tablet formulation of TAK-117 (new clinical trial material [NTM]) compared to the TAK-117 Process B capsules (current clinical trial material [CTM]) (Part 1), to assess the effects of food on the oral bioavailability and pharmacokinetics (PK) of TAK-117 (Part 2), and to assess the effects of gastric pH-modifying agent on the PK of TAK-117 in healthy participants (Part 3).
The drug being tested in this study is called TAK-117. TAK-117 is being tested to treat people who have advanced solid tumors. This study will look at the PK and relative bioavailability of new tablet formulation of TAK-117 as compare to current capsule formulation in Part 1. In Part 2 and Part 3, interaction of TAK-117 with food and a gastric pH modifying agent will be evaluated respectively in healthy participants, and will commence only after the completion of Part 1.
The study will enroll approximately 54 participants. In Part 1, participants will be randomly assigned (by chance, like flipping a coin) to 1 of the 2 crossover sequences:
Part 2 and Part 3 will be evaluated only on the new tablet formulation of TAK-117 at the dose determined in Part 1. In Part 2, participants will be randomly assigned to receive a single dose of TAK-117 in the fasted state followed by TAK-117 with standard high-fat breakfast in Sequence A or vice-versa in Sequence B. In Part 3, participants will receive a single dose of TAK-117 on Day 1 followed by lansoprazole 30 mg on Day 10 for 6 days and then second dose of TAK-117 on Day 15. Blood samples will be collected at predose and up to 72 hours postdose at prespecified time points on Days 1 and 15. Urine samples will be collected predose, 0 to 12 hours, and 12 to 24 hours postdose in Part 1 only.
This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 45 days. Participants will make 2 visits to the clinic in each part, during which they will remain confined to the clinic for a 4 to 10 day period for drug dosing and other study procedures. Participants will also complete a final visit 30 to 33 days after their last dose of study drug for a follow-up assessment (Day 45).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: TAK-117 9*100 mg + TAK-117 3*300 mg | Experimental | TAK-117900 milligram (mg), capsules, orally, once on Day 1, followed by 2 weeks of washout, followed by TAK-117 900 mg, tablets, orally, once on Day 15. |
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| Part 1: TAK-117 3*300 mg + TAK-117 9*100 mg | Experimental | TAK-117 900 mg tablets, orally, once on Day 1, followed by 2 weeks of washout, followed by TAK-117 900 mg, capsules, orally, once on Day 15. |
|
| Part 2: TAK-117 Fasted + TAK-117 Fed | Experimental | TAK-117 at the dose determined in Part 1, tablets, in fasted condition, orally, once on Day 1, followed by 2 weeks of washout, followed by TAK-117 at the dose determined in Part 1, tablets, with a standard high-fat meal, orally, once on Day 15. |
|
| Part 2: TAK-117 Fed + TAK-117 Fasted | Experimental | TAK-117 at the dose determined in Part 1, tablets, with a standard high-fat meal, orally, once on Day 1, followed by 2 weeks of washout, followed by TAK-117 at the dose determined in Part 1, tablets, in fasted condition, orally, once on Day 15. |
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| Part 3: TAK-117 + Lansoprazole | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-117 | Drug | TAK-117 capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for TAK-117 | Part 1 and 2: Day 1 or 15 pre-dose and at multiple time points (up to 72 hours) post-dose; Part 3: Day 1 (TAK-117) and Day 15 (TAK-117 + Lansoprazole) pre-dose and at multiple time points (up to 72 hours) post-dose | |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | Part 1 and 2: Day 1 or 15 pre-dose and at multiple time points (up to 72 hours) post-dose; Part 3: Day 1 (TAK-117) and Day 15 (TAK-117 + Lansoprazole) pre-dose and at multiple time points (up to 72 hours) post-dose | |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117 | Part 1 and 2: Day 1 or 15 pre-dose and at multiple time points (up to 72 hours) post-dose; Part 3: Day 1 (TAK-117) and Day 15 (TAK-117 + Lansoprazole) pre-dose and at multiple time points (up to 72 hours) post-dose | |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | Part 1 and 2: Day 1 or 15 pre-dose and at multiple time points (up to 72 hours) post-dose; Part 3: Day 1 (TAK-117) and Day 15 (TAK-117 + Lansoprazole) pre-dose and at multiple time points (up to 72 hours) post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Renal Clearance (CLr) of TAK-117 | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Takeda | Study Director |
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Healthy participants were enrolled in this 3-part study to receive TAK-117 in Part 1 as: Crossover of 9*100 milligram (mg) capsules or 3*300 mg tablets, Part 2: Crossover of TAK-117 in fasted or fed state and Part 3: TAK-117 with lansoprazole.
Participants took part in the study at 1 investigative site in the United States from 08 January 2016 to 22 July 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part-1: TAK-117 900 mg Capsules + TAK-117 900 mg Tablets | TAK-117 9*100 mg, capsules (current clinical trial material [CTM]), orally, once on Day 1 (first intervention), followed by washout from Day 2 to Day 14, further followed by TAK-117 3*300 mg, tablets (new clinical trial material [NTM]), orally, once on Day 15 (second intervention). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention (Day 1) |
|
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TAK-117 at the dose determined in Part 1, tablets, orally, once on Day 1, followed by lansoprazole 30 mg, tablets or capsules, once daily from Day 10 to Day 15, followed by TAK-117 at the dose determined in Part 1, tablets, orally, once on Day 15.
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| Lansoprazole | Drug | Lansoprazole capsules |
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| TAK-117 | Drug | TAK-117 tablets |
|
| FG001 |
| Part-1: TAK-117 900 mg Tablets + TAK-117 900 mg Capsules |
TAK-117 3*300 mg, tablets (NTM), orally, once on Day 1 (first intervention), followed by washout from Day 2 to Day 14, further followed by TAK-117 9*100 mg, capsules (CTM), orally, once on Day 15 (second intervention). |
| FG002 | Part-2: TAK-117 600 mg Fasted + TAK-117 600 mg Fed | TAK-117 2*300 mg, tablets (NTM), orally, once in the fasted state on Day 1 (first intervention), followed by washout from Day 2 to Day 14, further followed by TAK-117 2*300 mg, tablets (NTM), orally, with a standard high-fat breakfast, once on Day 15 (second intervention). |
| FG003 | Part-2: TAK-117 600 mg Fed + TAK-117 600 mg Fasted | TAK-117 2*300 mg, tablets (NTM), orally, once with a standard high-fat breakfast on Day 1 (first intervention), followed by washout from Day 2 to Day 14, further followed by TAK-117 2*300 mg, tablets (NTM), orally, in the fasted state, once on Day 15 (second intervention). |
| FG004 | Part-3: TAK-117 900 mg + Lansoprazole 30 mg | TAK-117 3*300 mg, tablets (NTM), orally, once on Day 1, followed by lansoprazole 30 mg, capsule, orally, once daily from Day 10 to Day 15 along with TAK-117 3*300 mg, tablets (NTM), orally, once on Day 15 approximately 1 hour (hr) after the last dose of lansoprazole 30 mg. |
| COMPLETED |
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| NOT COMPLETED |
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| Washout (Day 2 to Day 14) |
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| Second Intervention (Day 15) |
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Safety analysis population included all the participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part-1: TAK-117 900 mg Capsules + TAK-117 900 mg Tablets | TAK-117 9*100 mg, capsules (current clinical trial material [CTM]), orally, once on Day 1 (first intervention), followed by washout from Day 2 to Day 14, further followed by TAK-117 3*300 mg, tablets (new clinical trial material [NTM]), orally, once on Day 15 (second intervention). |
| BG001 | Part-1: TAK-117 900 mg Tablets + TAK-117 900 mg Capsules | TAK-117 3*300 mg, tablets (NTM), orally, once on Day 1 (first intervention), followed by washout from Day 2 to Day 14, further followed by TAK-117 9*100 mg, capsules (CTM), orally, once on Day 15 (second intervention). |
| BG002 | Part-2: TAK-117 600 mg Fasted + TAK-117 600 mg Fed | TAK-117 2*300 mg, tablets (NTM), orally, once in the fasted state on Day 1 (first intervention), followed by washout from Day 2 to Day 14, further followed by TAK-117 2*300 mg, tablets (NTM), orally, with a standard high-fat breakfast, once on Day 15 (second intervention). |
| BG003 | Part-2: TAK-117 600 mg Fed + TAK-117 600 mg Fasted | TAK-117 2*300 mg, tablets (NTM), orally, once with a standard high-fat breakfast on Day 1 (first intervention), followed by washout from Day 2 to Day 14, further followed by TAK-117 2*300 mg, tablets (NTM), orally, in the fasted state, once on Day 15 (second intervention). |
| BG004 | Part-3: TAK-117 900 mg + Lansoprazole 30 mg | TAK-117 3*300 mg, tablets (NTM), orally, once on Day 1, followed by lansoprazole 30 mg, capsule, orally, once daily from Day 10 to Day 15 along with TAK-117 3*300 mg, tablets (NTM), orally, once on Day 15 approximately 1 hour (hr) after the last dose of lansoprazole 30 mg. |
| BG005 | 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, Customized | Number | participants |
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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 | Number | participants |
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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 TAK-117 | The pharmacokinetic (PK)-evaluable population included participants who received both doses of TAK-117 study drug in each sequence and had sufficient PK data to reliably estimate PK parameters that were used for PK analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Part 1 and 2: Day 1 or 15 pre-dose and at multiple time points (up to 72 hours) post-dose; Part 3: Day 1 (TAK-117) and Day 15 (TAK-117 + Lansoprazole) pre-dose and at multiple time points (up to 72 hours) post-dose |
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| Primary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117 | The PK-evaluable population included participants who received both doses of TAK-117 study drug in each sequence and had sufficient PK data to reliably estimate PK parameters that were used for PK analyses. | Posted | Median | Full Range | hours | Part 1 and 2: Day 1 or 15 pre-dose and at multiple time points (up to 72 hours) post-dose; Part 3: Day 1 (TAK-117) and Day 15 (TAK-117 + Lansoprazole) pre-dose and at multiple time points (up to 72 hours) post-dose |
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| Primary | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-117 | The PK-evaluable population included participants who received both doses of TAK-117 study drug in each sequence and had sufficient PK data to reliably estimate PK parameters that were used for PK analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | Part 1 and 2: Day 1 or 15 pre-dose and at multiple time points (up to 72 hours) post-dose; Part 3: Day 1 (TAK-117) and Day 15 (TAK-117 + Lansoprazole) pre-dose and at multiple time points (up to 72 hours) post-dose |
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| Primary | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-117 | The PK-evaluable population where data at specified time points were available. The PK-evaluable population included participants who received both doses of TAK-117 study drug in each sequence and had sufficient PK data to reliably estimate PK parameters that were used for PK analyses. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Part 1 and 2: Day 1 or 15 pre-dose and at multiple time points (up to 72 hours) post-dose; Part 3: Day 1 (TAK-117) and Day 15 (TAK-117 + Lansoprazole) pre-dose and at multiple time points (up to 72 hours) post-dose |
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| Secondary | Part 1: Renal Clearance (CLr) of TAK-117 | The PK-evaluable population included participants who received both doses of TAK-117 study drug in each sequence and had sufficient PK data to reliably estimate PK parameters that were used for PK analyses. | Posted | Mean | Standard Deviation | liter per hour (L/hr) | Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose |
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Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 30 days (Day 46) after the last dose of study drug
At each visit, investigator had to document any occurrence of adverse events and abnormal laboratory findings.Any event spontaneously reported by participant/observed by investigator was recorded,irrespective of relation to study treatment.Number at risk included those participants who have actually received the mentioned intervention during study.
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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 | Part-1: TAK-117 900 mg Capsules | TAK-117 9*100 mg, capsules (CTM), orally, once on Day 1 or 15 of intervention period. | 0 | 19 | 3 | 19 | ||
| EG001 | Part-1: TAK-117 900 mg Tablets | TAK-117 3*300 mg, tablets (NTM), orally, once on Day 1 or 15 of intervention period. | 0 | 18 | 5 | 18 | ||
| EG002 | Part-2: TAK-117 600 mg Fasted | TAK-117 2*300 mg, tablets (NTM), orally, once in a fasted state on Day 1 or 15 of intervention period. | 0 | 17 | 8 | 17 | ||
| EG003 | Part-2: TAK-117 600 mg Fed | TAK-117 2*300 mg, tablets (NTM), orally, with a standard high-fat breakfast, once on Day 1 or 15 of intervention period. | 0 | 17 | 4 | 17 | ||
| EG004 | Part-3: TAK-117 900 mg | TAK-117 3*300 mg, tablets (NTM), orally, once on Day 1. | 0 | 16 | 6 | 16 | ||
| EG005 | Part-3: Lansoprazole 30 mg | Lansoprazole 30 mg, capsule, orally, once daily from Day 10 to Day 14. | 0 | 16 | 1 | 16 | ||
| EG006 | Part 3: Lansoprazole 30 mg + TAK-117 900 mg | Lansoprazole 30 mg, capsule, orally, once daily on Day 15 along with TAK-117 3*300 mg, tablets (NTM), orally, once on Day 15. | 0 | 16 | 1 | 16 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Menstruation delayed | Reproductive system and breast disorders | MedDRA (18.0) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA (18.0) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Systematic Assessment |
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| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Vessel puncture site pain | General disorders | MedDRA (18.0) | Systematic Assessment |
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In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000627413 | serabelisib |
| D064747 | Lansoprazole |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Not provided
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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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Analysis of variance was performed for calculating 90% CIs for the ratios of log-transformed geometric mean Cmax of TAK-117 tablet dosage form with food versus without food.
| Geometric mean ratio |
| 1.20 |
| 2-Sided |
| 90 |
| 0.86 |
| 1.67 |
| Superiority or Other |
| Analysis of variance was performed for calculating 90% CIs for the ratios of log-transformed geometric mean Cmax of TAK-117 tablet dosage form with lansoprazole versus a single dose of TAK-117 alone. | Geometric mean ratio | 0.03 | 2-Sided | 90 | 0.02 | 0.07 | Superiority or Other |
TAK-117 2*300 mg, tablets (NTM), orally, with a standard high-fat breakfast, once on Day 1 or 15 of intervention period.
| OG004 | Part-3: TAK-117 900 mg (3*300 mg Tablets) | TAK-117 3*300 mg, tablets (NTM), orally, once on Day 1. |
| OG005 | Part-3: TAK-117 900 mg (3*300 mg Tablets) + Lansoprazole 30 mg | Lansoprazole 30 mg, capsule, orally, once daily from Day 10 to Day 15 along with TAK-117 3*300 mg, tablets (NTM), orally once on Day 15. |
|
|
| Part-2: TAK-117 600 mg Fed (2*300 mg Tablets) |
TAK-117 2*300 mg, tablets (NTM), orally, with a standard high-fat breakfast, once on Day 1 or 15 of intervention period. |
| OG004 | Part-3: TAK-117 900 mg (3*300 mg Tablets) | TAK-117 3*300 mg, tablets (NTM), orally, once on Day 1. |
| OG005 | Part-3: TAK-117 900 mg (3*300 mg Tablets) + Lansoprazole 30 mg | Lansoprazole 30 mg, capsule, orally, once daily from Day 10 to Day 15 along with TAK-117 3*300 mg, tablets (NTM), orally once on Day 15. |
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| Part-2: TAK-117 600 mg Fed (2*300 mg Tablets) |
TAK-117 2*300 mg, tablets (NTM), orally, with a standard high-fat breakfast, once on Day 1 or 15 of intervention period. |
| OG004 | Part-3: TAK-117 900 mg (3*300 mg Tablets) | TAK-117 3*300 mg, tablets (NTM), orally, once on Day 1. |
| OG005 | Part-3: TAK-117 900 mg (3*300 mg Tablets) + Lansoprazole 30 mg | Lansoprazole 30 mg, capsule, orally, once daily from Day 10 to Day 15 along with TAK-117 3*300 mg, tablets (NTM), orally once on Day 15. |
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